EFFICACY OF 3% MEPIVACAINE PLUS 2% WITH 1:100,000 EPINEPHRINE FOR INFERIOR ALVEOLAR NERVE BLOCKS

A Thesis

Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science

in the Graduate School of The Ohio State University

By

Emily Theresa Lammers, D.D.S.

Graduate Program in Dentistry

The Ohio State University 2013

Master’s Examination Committee:

John Nusstein, D.D.S., M.S., Advisor

Al Reader, D.D.S., M.S.

Melissa Drum, D.D.S., M.S.

F. Michael Beck, D.D.S., M.A.

Copyright by

Emily Theresa Lammers, D.D.S.

2013

ABSTRACT

Introduction: Combinations of are used clinically to potentially increase the success of pulpal anesthesia and decrease the pain of injection. The purpose of this study was to evaluate the combination of mepivacaine and lidocaine when used for inferior alveolar nerve blocks. Materials and Methods: One hundred asymptomatic subjects were given 1.8 mL 3% mepivacaine plus 1.8 mL 2% lidocaine with 1:100,000 epinephrine or two injections of 1.8 mL 2% lidocaine with 1:100,000 epinephrine for the IANB at two separate appointments spaced at least one week apart. Subjects rated the pain of needle insertion, needle placement, and solution deposition on a Heft-Parker VAS. The first and second molars, first and second premolars, and incisors were tested with an EPT every 4 minutes for 56 minutes post-injection for pulpal anesthesia. Anesthetic success was considered to occur when the subject achieved two consecutive 80 readings within 15 minutes of injection and sustained the 80 reading for the remainder of the testing period. Results: Mean injection pain was in the mild pain range for both anesthetic combinations, with the exception of needle placement pain in females, which was moderate. No significant differences in injection pain were seen between the two groups. Anesthetic success was not significantly different between the anesthetic groups in any of the teeth tested. Summary and Conclusions: The combination of 3% mepivacaine and 2% lidocaine with 1:100,000 epinephrine is equivalent to 2% lidocaine with 1:100,000 epinephrine in terms of injection pain and pulpal anesthetic success for the IANB .

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DEDICATION

To Maxwell- you are a beautiful child, inside and out. You have changed my life in so many ways. You are the reason for everything that I do, and I can’t wait to see what life has in store for you.

To Philip- you are my best friend, a wonderful husband, and an amazing father. Thank you for your constant support, and for loving me unconditionally.

To my parents- you were my first teachers. Thank you for instilling me with a love of learning, and for always supporting me.

I love you all.

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ACKNOWLEDGEMENTS

Dr. Nusstein- It has been a pleasure working with you for the past three years. Thank you for your constant encouragement and guidance. You have been a wonderful mentor, and your dedication to this department is apparent in all of the hard work that you do. You have certainly earned that golden squirrel!

Dr. Reader- Thank you for welcoming me to your endo family, and for always making me laugh! I feel so lucky to have learned from the best. You are the reason that Ohio State Endodontics has such an outstanding reputation.

Dr. Drum- Not only are you an amazing teacher, but a great friend. Thank you for sharing your knowledge and for always being there. I hope you know how special you are to this program.

Dr. Beck- Thank you for making the world of statistics a little less confusing! I’m sure I couldn’t have completed this project without your help. It was a pleasure getting to know you.

Dr. Fowler- I am so happy that you have found your niche in education! You are a wonderful teacher, and this program is lucky to have you. Thank you for all of your advice and for your friendship.

To my co-residents: Brett, Shayne, and Vivian- Thank you for two years of friendship, laughter, and of course, tacos. I wish you all the best in your careers and in life.

Thank you to all of the dental students, especially: Chase, Jeff, Tommy, Sahar, Brandon, Jason, and Kurt. Without you, I would probably still be pulp testing.

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VITA

July 22, 1985………………………………………. Born: Lima, Ohio

2003-2006…………………………………………..The Ohio State University College of Arts and Sciences

2010…………………………………………………Doctor of Dental Surgery, The Ohio State University Columbus, Ohio

2013…………………………………………………Master of Science & Specialization in Endodontics Post-Doctoral Certificate, The Ohio State University, Columbus, Ohio

FIELD OF STUDY

Major Field: Dentistry

Specialization: Endodontics

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TABLE OF CONTENTS

Page

Abstract……………………………………………………………………………………ii Dedication……………………………………………………………………………...…iii Acknowledgements……………………………………………………………………….iv Vita…………………………………………………………………………………….…..v Table of Contents………………………………………………………………………...vi List of Tables……………………………………………………………………...... vii List of Figures………………………………………………………………………….....ix Chapters: 1. Introduction……………………………………………………………..1 2. Literature Review……………………………………………………….3 3. Materials and Methods………………………………………………..58 4. Results…………………………………………………………………64 5. Discussion……………………………………………………………..69 6. Summary and Conclusions…………………………………………..104 Appendices: A. Tables………………………………………………………………..106 B. Figures…………………………………………………………….....125 C. Medical History Form………………………………………….……132 D. Consent Form…………………………………………………..……135 E. HIPAA Privacy Form……………………………………..…………142 F. Heft-Parker VAS Form…………………………………………..…..146 G. Electric Pulp Testing Form…………………………………...……..148 H. Raw Data……………………………………………………...……..152 References………………………………………………………………………………243

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LIST OF TABLES

Table Page

5-1. Needle insertion pain reported by category………………………….………..…74 5-2. Needle placement pain reported by category………………………….…….…..76 5-3. Solution deposition pain reported by category………………………………..…82 5-4. Mean onset times for pulpal anesthesia of IANB……………………………..…94 5-5. Incidence of anesthesia of slow onset for IANB……………………………...... 98 5-6. Incidence of non-continuous anesthesia for IANB…………………….……..….99 5-7. Incidence of anesthesia of short duration with IANB……………….………….100 A-1. Biographical data for all subjects…………………………………..………..….107 A-2. Mean pain ratings for first injection………………………………………….....108 A-3. Mean pain ratings for second injection………………………….………..…….109 A-4. Injection pain (first injection)………………………………………..…………110 A-5. Injection pain (second injection)……………………………..…………………111 A-6. Anesthetic success………………………………………..………………..…...112 A-7. Anesthetic failure……………………………………………..……………...... 113 A-8. Central incisors 80/80 pulp tester readings…………………………..……..….114 A-9. Lateral incisors 80/80 pulp tester readings…………………………………..…115 A-10. First premolars 80/80 pulp tester readings…………………………...... …116 A-11. Second premolars 80/80 pulp tester readings………………………………..…117 A-12. First molars 80/80 pulp tester readings………………………………………....118 A-13. Second molars 80/80 pulp tester readings………………………………...…....119 A-14. Onset of anesthesia………………………………………………………...... …120 A-15. Duration of anesthesia………………………..…………………………..……..121 A-16. pH of anesthetic solutions………………………..…………………………...... 122

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A-17. Pulpal anesthesia success rates with 2% lidocaine with 1:100,000 epinephrine and with 3% mepivacaine for IANB……………………………………………………123 A-18. Pulpal anesthesia failure rates with 2% lidocaine with 1:100,000 epinephrine and with 3% mepivacaine for IANB…………………………………………………....124

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LIST OF FIGURES

Figure Page

1. Pulpal anesthesia by time for central incisor……………………………………....126 2. Pulpal anesthesia by time for lateral incisor……………………………………….127 3. Pulpal anesthesia by time for first premolar……………………………………….128 4. Pulpal anesthesia by time for second premolar…………………………………....129 5. Pulpal anesthesia by time for first molar…………………………………………..130 6. Pulpal anesthesia by time for second molar………………………………………..131

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INTRODUCTION

The inferior alveolar nerve (IAN) block is the most frequently used injection

technique for achieving local anesthesia for mandibular restorative and surgical

procedures. However, the IAN block does not always result in successful pulpal

anesthesia (1). Failure rates of 10% to 39% have been reported in experimental studies

(1). Clinical studies in endodontics (2-14) have found success with the IAN block

occurring between 15% and 57% of the time. Therefore, it would be advantageous to

improve the success rate of the inferior alveolar nerve block.

Some clinicians combine 3% mepivacaine plain with 2% lidocaine with

1:100,000 epinephrine for IAN blocks (15). The thought is that 3% mepivacaine has

more anesthetic molecules than 2% lidocaine because of its higher concentration and that

it also has a higher pH because it does not contain epinephrine. Both of these concepts

would supposedly provide more of the base molecules for the IAN block initially –

therefore potentiating the effect of administration of the second cartridge of 2% lidocaine

with 1:100,000 epinephrine. Two studies found that 3% mepivacaine was equivalent to

2% lidocaine with 1:100,000 epinephrine for an inferior alveolar nerve block (4,16).

Rood and coauthors (17) found there was no potentiation of lidocaine with epinephrine by adding 4% plain for dental extractions.

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No objective study has combined 3% mepivacaine and 2% lidocaine with

1:100,000 epinephrine for inferior alveolar nerve blocks. Therefore, the purpose of this prospective, randomized, double-blind study is to compare the degree of pulpal anesthesia obtained with a combination 3% mepivacaine/2% lidocaine with 1:100,000 epinephrine formulation versus 2% lidocaine with 1:100,000 epinephrine/2% lidocaine with 1:100,000 epinephrine formulation in inferior alveolar nerve blocks. Additionally, we will study injection pain of the two sets of IAN blocks.

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LITERATURE REVIEW

Local Anesthetics

MECHANISM OF ACTION OF LOCAL ANESTHETICS

The primary function of a is to reversibly block the initiation and

conduction of a nerve impulse (18, 19). The nerve impulse is dependent on the concentration of specific electrolytes in the intracellular and extracellular fluid spaces, as well as the permeability of the nerve membrane to these electrolytes (19). While the membrane is freely permeable to potassium and chloride ions, it is only slightly permeable to sodium ions. The resting potential of the membrane is maintained at -90 mV due to the high concentrations of K+ within the cell and Na+ outside the cell (18-21).

Stimulation or excitation of the nerve causes a transient widening of transmembrane channels which allow sodium ions to pass through. This results in a decrease in the negative transmembrane potential. If the potential change is great enough to reach the firing threshold of -55 mV, membrane permeability to sodium increases dramatically and a large influx of sodium ions occurs. This results in a reversed electrical potential of +40 mV across the membrane (19-24). This process, known as depolarization, takes approximately 0.3 milliseconds (20).

At this point the permeability of the membrane to K+ increases, resulting in the efflux of potassium ions. The transmembrane channels enter an inactive state in which

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they are unable to respond to another stimulus. This is known as the absolute refractory

period. By the time the membrane returns to a resting potential of -60 to -90 mV, the

channels have returned to a closed resting form (20, 22). This process of repolarization

occurs in approximately 0.7 milliseconds (20).

After the membrane has returned to its resting potential, a slight excess of sodium

exists within the nerve cell, and a slight excess of potassium exists extracellularly. The

sodium pump actively transfers sodium ions out of the cell using energy from the

oxidative metabolism of adenosine triphosphate (19, 20, 23). The electrical imbalance

that is created disrupts the resting equilibrium of the adjacent area of the nerve, causing

cycles of depolarization and repolarization that propagate an impulse along the nerve.

Due to the refractory period of each nerve segment, the conduction of the impulse can only proceed in one direction (20).

Local anesthetics affect the nerve by reducing the passage of sodium into the cell

(18-20, 24-27). The specific action of local anesthetics on the nerve membrane has not been clearly established (22-24, 28); however, there are currently two theories that may explain the mechanism (20, 24, 28). The membrane expansion theory states that local anesthetic molecules prevent an increase in membrane permeability to sodium ions by diffusing into critical areas of the membrane and decreasing the diameter of sodium channels. This is hypothesized to occur due to the distortion or expansion of membrane proteins, leading to the inhibition of sodium passage and therefore, neural excitation (20,

23, 25). The specific receptor theory, which is more widely accepted, states that local anesthetics bind to specific receptors on the internal surface of the open .

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This either blocks the sodium channels or causes them to close, resulting in

impermeability of the membrane to sodium ions (19, 20, 24, 27-29). Biotoxins, such as and , support this theory as they have been shown to irreversibly bind at a receptor site on the external surface of the nerve membrane (19, 27, 29-32).

PHARMACOLOGY OF LOCAL ANESTHETICS

The local anesthetic molecule consists of three components: a lipophilic aromatic

ring, an intermediate hydrocarbon chain, and a hydrophilic terminal amine group (19, 20,

22, 26). The aromatic ring makes the molecule lipid soluble, and can be enhanced by

aliphatic substitutions. Lipid solubility promotes diffusion through the nerve sheath and

allows more molecules to enter the neuron; therefore, greater lipid solubility makes the

local anesthetic more potent (26).

The intermediate chain contains either an ester or an amide linkage, and thus the

molecule is classified an amino-ester or an amino-amide anesthetic (20). Amino-ester

anesthetics, with the exception of topical , are rarely used clinically today

(26). These compounds are hydrolyzed by plasma esterases to form para-aminobenzoic acid, or PABA, which has been implicated in causing allergic reactions. Amino-amide anesthetics, such as lidocaine and mepivacaine, are biotransformed in the liver and excreted in the urine. PABA is not formed from amide anesthetics so allergic reactions are extremely rare (19). is a unique amide anesthetic as it contains a thiophene ring which allows the molecule to better diffuse through the lipid-rich nerve membrane,

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and an ester group which facilitates hydrolyzation in the plasma before excretion by the

kidneys (26, 33).

The terminal amine group exists in either a tertiary or quaternary form, which

allows the local anesthetic to conform to a lipid-soluble or water-soluble state (26).

Alone, local anesthetics are weakly basic compounds which are insoluble in water (20).

To increase solubility and stability, they are formulated as hydrochloride salts (20, 26).

The majority of injectable local anesthetics are tertiary amines (18, 20). In solution, the

local anesthetic salt exists in two forms: the quaternary cation form which is positively

charged and therefore water soluble, and the tertiary base form which is uncharged and

lipid soluble (18, 19, 26, 27). The balance between the two forms is dependent on the

environmental pH (29). The pKa, or dissociation constant, is the pH at which 50% of

each form is present (19, 26, 27). Each local anesthetic has a specific pKa, and for most

anesthetic solutions it is between 7.5 and 9 (22, 27). When exposed to physiologic pH of

7.4, more of the uncharged base form of the anesthetic will be present and this form is able to diffuse through the nerve sheath (19, 26). Once inside the nerve, equilibrium between the two forms reoccurs and the charged cation form binds to the receptor site on the nerve membrane to cause local anesthesia (19, 29).

SAFETY OF LOCAL ANESTHETICS

Many adverse reactions associated with local anesthetics are not due to the drugs themselves (formulation), but to the drug concentration or the act of drug administration

(34, 35). Local complications, such as post-injection neuropathy or paresthesia, trismus,

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hematoma, facial nerve paralysis, and soft tissue injury have been reported following

injections (34). In a study by Garisto et al. (35), 94.5% of reported adverse anesthetic events were associated with mandibular nerve blocks; this trend has been reported by other studies as well (36, 37).

Paresthesias may manifest as total loss of sensation, burning or tingling feeling, or pain in response to normal stimuli (38). It is speculated that the incidence of non-surgical

paresthesia in dentistry occurs in 1:785,000 to 1:26,000 patients, but the actual number is

unknown (34, 36, 39). While the exact cause of paresthesia is unknown, it appears to be

associated with local anesthetic administration and is almost exclusively related to the

inferior alveolar nerve block injection (34, 36). Current hypotheses include direct trauma

to the nerve from the needle, hemorrhage into the neural sheath, and neurotoxicity

associated with a local anesthetic (34, 38). Some authors have concluded that the

incidence of paresthesia is associated with higher concentrations of local anesthetic (35,

38). Approximately 85-94% of paresthesias resolve spontaneously within 8 weeks, but

two-thirds of those who do not recover quickly may never recover (39).

Trismus and soft tissue injury may occur following the inferior alveolar nerve

(IAN) block injection; this can be caused by hematoma formation subsequent to damage

to the inferior alveolar artery or vein, multiple injections or intramuscular injection

causing damage to the muscle fibers, or excessive volume of local anesthetics (40, 41).

Facial nerve paralysis has been reported in patients when local anesthetic was deposited

into the parotid gland; this resolved as the anesthetic was redistributed (40).

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A true allergic reaction to amide local anesthetics is extremely rare, as these

reactions are mainly seen with ester anesthetics or anesthetics stored in multi-dose vials

with paraben preservatives (40-42). The most common sign of an allergic reaction is a

skin reaction; however, bronchospasm and anaphylaxis can occur (40). Adverse reactions

such as fear and anxiety, intravascular injection, toxic overdose, and sensitivity to

epinephrine are often mistaken for a true allergy (41). Some patients may have an allergic

reaction caused by sulfite preservatives in anesthetic solutions that contain epinephrine

(40, 41). Mild allergic reactions can be treated with antihistamines, while acute reactions

necessitate activation of an emergency response system (41).

Toxicity from local anesthetics can be seen following excessive dosing,

intravascular injection, or with rapid systemic absorption due to the absence of a

vasoconstrictor (41). Symptoms are dose-dependent and include drowsiness, numbness of the lips and tongue, metallic taste in the mouth, double vision, nystagmus, tremors, and eventual grand mal convulsions and impaired circulation due to anesthetic-induced cardiovascular depression (42). Mepivacaine and prilocaine are commonly associated with toxicity due to the higher concentration of anesthetic and lack of epinephrine; however, toxicity can result from an overdose with any anesthetic (20, 41). Overdosage is

reported more often in children when doses are not adjusted to the child’s weight, or

when an anesthetic without a vasoconstrictor is selected and multiple injections are given

due to the short duration of these anesthetics. In adults, the maximum recommended dose

of lidocaine is 500 mg (6.6 mg/kg), mepivacaine is 400 mg (6.6 mg/kg), and articaine is

500 mg (7.0 mg/kg) (20).

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Vasoconstrictors, such as epinephrine, are added to local anesthetics to improve

efficacy, increase the duration of anesthesia, and lessen systemic toxicity (28, 40, 42).

Epinephrine stimulates alpha-1 and alpha-2 receptors in the walls of arterioles causing

them to constrict, which decreases blood flow locally (43). While this is beneficial in slowing the absorption of local anesthetic, it can be dangerous in patients with reduced cardiovascular function as epinephrine also stimulates beta-1 receptors causing increased heart rate and contractility (40, 43, 44). It is recommended that a local anesthetic

containing epinephrine be limited to two 1.8 mL cartridges in patients with

cardiovascular disease (40). In patients taking non-selective beta blockers, epinephrine administration may result in a significant increase of blood pressure. Drug interactions may also be seen in patients taking tri-cyclic antidepressants (43). Adverse effects of

epinephrine include tachycardia, tremor, palpitations, arrhythmia, anxiety, headache, and

hypertension (40).

Pregnancy is a relative contraindication to elective dental care; however, local anesthetics and vasopressors may be administered during any trimester (20). All local

anesthetics are able to cross the placental barrier by passive diffusion (45). Lidocaine is

listed as a Category B drug by the FDA, which states “Animal studies show no risk or

adverse fetal effects but controlled human first trimester studies not available/do not

confirm; no evidence of second or third trimester risk; fetal harm possible but unlikely”.

Mepivacaine is classified as Category C, and its use is recommended with caution (20).

Possible complications of mepivacaine include fetal bradycardia. The use of benzocaine is also cautioned in pregnant patients due to the risk of methemoglobinemia and possible

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hypoxemia in both the mother and fetus. High amounts of vasoconstrictors can decrease

uterine blood flow, but up to 0.1 mg of epinephrine can be used safely in healthy

pregnant patients (45).

INFERIOR ALVEOLAR NERVE BLOCK

The most common injection for obtaining mandibular anesthesia is the inferior

alveolar nerve block (20). The site of injection is the soft tissue overlying the medial

surface of the ramus, lateral to the pterygomandibular raphe, at a height determined by

the coronoid notch on the anterior border of the ramus. Once the subject’s mouth is wide open, the thumb of the non-injecting hand is placed over the pterygomandibular triangle and then pulled laterally until a depression in the anterior border of the ramus is felt. The posterior portion of the ramus is palpated with the first or second finger of the non- injecting hand until a slight depression is located. The vertical height of the injection site is determined by the line between the thumb and the finger. The direction of the needle insertion is from the contralateral mandibular premolars and aligned parallel to the occlusal plane (46). The needle is advanced until bone is sounded, then retracted 1 mm before aspiration and injection into the pterygomandibular space (20). The conventional inferior alveolar nerve block will anesthetize the inferior alveolar nerve, mental nerve, and the lingual nerve. This would include pulpal anesthesia of mandibular molars, premolars, and incisors on the injected side, as well as the associated supporting bony and periodontal structures to the midline. It would also anesthetize the buccal and labial soft

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tissues and chin to the midline, and the contralateral anterior two-thirds of the tongue

(20).

INJECTION PAIN

Local anesthetics are the most important and most frequently used drugs in a

dental practice. While their use leads to a relatively painless dental procedure, the

administration of anesthetics can be a source of anxiety and pain for many patients (47-

49). Different methods have been studied in an attempt to reduce pain during each stage

of an injection: insertion of the needle into the mucosa, placement of the needle to the

target site, and deposition of the local anesthetic solution.

NEEDLE INSERTION

The use of topical anesthetics has been studied to determine their effect on needle

insertion pain for the inferior alveolar nerve block (IANB) injection. Nusstein and Beck

(47) evaluated the effectiveness of 20% benzocaine as a topical anesthetic in a

retrospective study. One thousand six hundred and thirty-five IANB injections were given; 470 of these received topical anesthetic, whereas 1165 did not. While 14-22% of subjects reported moderate-to-severe pain to needle insertion, there was no significant difference between the two groups for the IANB injection.

The following studies evaluated needle insertion pain for IANB injections utilizing 2% lidocaine with 1:100,000 epinephrine. The type of anesthetic being injected should not have an impact on needle insertion pain. Factors that must be considered when

11

evaluating needle insertion pain include needle gauge, use of topical anesthetic, operator

differences, and gender of the subject.

Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL)

injection after an IANB injection. Forty asymptomatic subjects recorded pain of needle

insertion with a 27-gauge needle during the IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain during needle insertion was reported in 25% of injections, mild pain in 58.75%, moderate pain in 13.75%, and severe pain in 2.5% of injections.

Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection following an IANB injection. Forty asymptomatic subjects recorded pain of needle insertion with a 27-gauge needle during the IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain during needle insertion was reported in 43% of injections, mild pain in 53%, moderate pain in 5%, and severe pain in 0% of injections.

Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following an IANB injection. Thirty-eight asymptomatic subjects recorded pain of needle insertion with a 27-gauge needle during the IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in the study.

No pain during needle insertion was reported in 32% of injections, mild pain in 58%, moderate pain in 10%, and severe pain in 0% of injections.

Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block and the combination IANB/MN block. Thirty asymptomatic subjects recorded pain of

12 needle insertion with a 27-gauge needle during the IANB injection utilizing a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain during needle insertion was reported in 28.8% of injections, mild pain in 53.1%, moderate pain in 14.4%, and severe pain in 3.8% of injections.

Willett (54) studied the anesthetic efficacy of and the combination diphenhydramine/lidocaine for the IANB injection. Thirty asymptomatic subjects recorded pain of needle insertion with a 27-gauge needle on a four-point scale

(0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain during needle insertion was reported in 29% of injections, mild pain in 58%, moderate pain in 12%, and severe pain in 1% of injections.

Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine versus a non-buffered solution for IANB injections. No topical anesthetic was used in this study. Subjects were asked to rate the discomfort of needle insertion with a 27-gauge needle on a 4-point scale

(0= no pain, 1= mild, 2= moderate, 3= severe). Patients reported no pain to needle insertion in 40% of injections, mild pain in 55%, moderate pain in 5%, and severe pain in

0% of injections.

Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB administered with a peripheral nerve stimulator. Forty-six asymptomatic patients each received a conventional IANB with a 22-gauge needle, and an IANB administered with the help of a peripheral nerve stimulator and a 22-gauge needle. No topical anesthetic

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was used in this study. Immediately after the injections, the subjects rated the pain of

needle insertion on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3=

severe pain). Needle insertion pain with the conventional IANB was rated as no pain by

16% of subjects, mild pain by 53%, moderate pain by 29%, and severe pain by 3%.

Wolf (57) evaluated the anesthetic efficacy of mannitol and lidocaine with

epinephrine in IANB injections with a 27-gauge needle. Forty asymptomatic subjects

rated the pain of needle insertion on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain to needle insertion was reported in 31% of injections, mild pain in 55%, moderate pain in

14%, and severe pain in 0% of injections.

Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous injection following an IANB injection with a 27-gauge needle. Forty asymptomatic subjects recorded the pain of needle insertion during the IANB injection on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain to needle insertion was reported in 7% of injections, mild pain in 67%, moderate pain in 26%, and severe pain in 0% of injections.

Mikesell (59) evaluated the anesthetic efficacy of articaine and lidocaine for

IANB injections. Fifty-seven asymptomatic subjects recorded the pain of needle insertion with a 27-gauge needle during the IANB injection on a 170-mm Heft-Parker VAS form.

Topical anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds.

No pain was reported in 6% of injections, mild pain in 65%, moderate pain in 29%, and

14 severe pain in 0% of injections. The mean VAS score was 38.7 mm, which was in the mild range.

Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for

IAN blocks. Fifty-two asymptomatic subjects recorded the pain of needle insertion with a

27-gauge needle during the IANB injection on a 170-mm Heft-Parker VAS form. Topical anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds. No pain during needle insertion was reported in 4% of injections, mild pain in 84%, moderate pain in 11%, and severe pain in 1% of injections. The mean VAS score was 37.5 mm, which was in the mild range.

Steinkruger (61) evaluated the significance of needle bevel orientation in achieving a successful IAN block. Fifty-one asymptomatic subjects each recorded the pain of needle insertion with a 27-gauge needle during the IANB injection on a 170-mm

Heft-Parker VAS form. Topical anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds. Regarding the one-stage injection, no pain during needle insertion was reported in 7.8% of injections, mild pain in 84.3%, moderate pain in 7.8%, and severe pain in 0% of injections. The mean VAS score was 34 mm, which was in the mild range.

Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an

IANB injection. Ninety asymptomatic subjects rated the pain of needle insertion with a

27-gauge needle on a 170-mm Heft Parker VAS form. Topical anesthetic (20% benzocaine) was placed at the injection site for 60 seconds. The mean VAS score was 44

15 mm, which was in the mild range. Subjects reported none-to-mild pain in 64% of insertions, and moderate-to-severe pain in 36% of insertions.

Vreeland and coauthors (63) evaluated the anesthetic efficacy of different volumes and concentrations of lidocaine in the IAN block. Thirty asymptomatic subjects each received an IANB injections of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine,

3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and 1.8 mL of 4% lidocaine with

1:100,000 epinephrine at 3 separate appointments. Topical anesthetic (20% benzocaine) was placed at the injection site for 30 seconds. Each subject was asked to rate the pain of needle insertion with a 27-gauge needle on a three-point scale (1= no-to-mild pain, 2= moderate pain, 3= severe pain). Although the phases of needle insertion and needle placement were not separated in this study, 63.3% of subjects reported no-to-mild pain,

31.1% reported moderate pain, and 5.5% reported severe pain.

Hinkley (64) evaluated 4% prilocaine with 1:200,000 epinephrine, 2% mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with 1:100,000 epinephrine for the IANB injection. Thirty asymptomatic subjects rated the pain of needle insertion with a 27-gauge needle a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no distinction between needle insertion and needle placement in this study. No topical anesthetic was used in this study. No pain to needle insertion was reported in 21% of injections, mild pain in 67%, moderate pain in 11%, and severe pain in 1% of injections.

McLean (65) evaluated the efficacy of 4% prilocaine, 3% mepivacaine, and 2% lidocaine solutions for the IANB injection. Thirty asymptomatic subjects recorded the

16

pain of needle insertion with a 27-gauge needle on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no distinction between needle insertion and needle placement in this study. No topical anesthetic was used. No pain to needle insertion was reported in 9% of injections, mild pain in 50%, moderate pain in 34%, and severe pain in 7% of injections.

Yonchak (66) studied the anesthetic efficacy of unilateral and bilateral IAN blocks to determine cross innervation in anterior teeth. Forty asymptomatic subjects recorded the pain of needle insertion with a 27-gauge needle on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no distinction between needle insertion and needle placement in this study. No topical anesthetic was used in this study. No pain to needle insertion was reported in 6% of injections, mild pain in 49%, moderate pain in 40%, and severe pain in 5% of injections.

Goldberg and coauthors (67) compared the conventional inferior alveolar, Gow-

Gates, and Vazirani-Akinosi techniques for mandibular anesthesia. Forty asymptomatic subjects recorded the pain of needle insertion with a 27-gauge needle on a 4-point scale

(0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no distinction between needle insertion and needle placement in this study. Topical anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds. Needle insertion for the IANB was reported as none-to-mild pain in 77%, moderate pain in 22%, and severe pain in 0% of injections.

In the studies reviewed, no significant difference was seen with the use of topical anesthetic to reduce the pain of needle insertion. Although there were some operator

17

differences, a majority of subjects reported no-to-mild pain. Only one study analyzed the

effect of gender on pain reported, but no difference was seen in the pain reported between

males and females (62). A 27-gauge needle was used in all of the above studies;

therefore, no differences were seen regarding needle gauge.

NEEDLE PLACEMENT

Studies have looked at the pain of needle placement to the injection target site.

The main method attempted to reduce pain during this phase of an IANB injection has

been to deposit anesthetic solution as the needle is moved through the soft tissues. A two-

stage injection technique has also been studied in an attempt to reduce the pain of needle

placement during an IANB injection. The following studies looked at the pain of needle

placement during an IANB injection.

Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL) injection after an IANB. Forty asymptomatic subjects recorded pain of needle placement

during an IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No pain during needle placement was reported in 17.5% of injections, mild pain in 47.5%, moderate pain in 35%, and severe pain in 0% of injections.

Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection following an IAN block. Forty asymptomatic subjects recorded pain of needle placement during a conventional IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was

18

reached. No pain during needle placement was reported in 14% of injections, mild pain in

63%, moderate pain in 23%, and severe pain in 1% of injections.

Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following

an IANB injection. Thirty-eight asymptomatic subjects recorded pain of needle

placement during a conventional IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No pain during needle placement was reported in 40% of injections, mild pain in 45%, moderate pain in 15%, and severe pain in 0% of injections.

Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block and the combination IANB/MN block. Thirty asymptomatic subjects recorded pain of needle placement during a conventional IANB injection on a four-point scale (0= no pain,

1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No pain during needle placement was reported in 26% of injections, mild pain in 36%, moderate pain in 27%, and severe pain in 11% of injections.

Willett (54) studied the anesthetic efficacy of lidocaine, diphenhydramine, and the combination of diphenhydramine/lidocaine for the IANB injection. Thirty asymptomatic subjects recorded pain of needle placement on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No pain during needle placement was reported in 12.9% of injections, mild pain in 42.6%, moderate pain in 38.6%, and severe pain in 5.9% of injections.

Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB administered with the aid of a peripheral nerve stimulator. Forty-six asymptomatic

19 patients each received a conventional IANB and an IANB administered with the aid of a peripheral nerve stimulator. No anesthetic was deposited until the target site was reached.

Immediately after the injection, the subject rated the pain of needle placement on a 4- point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). Needle placement pain with the conventional IANB was rated as no pain by 11% of subjects, mild pain by 58%, moderate pain by 32%, and severe pain by 0%.

Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous injection following an IANB injection. Forty asymptomatic subjects recorded the pain of needle placement during an IANB injection on a 4-point scale (0= no pain, 1= mild pain,

2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No pain to needle placement was reported in 27% of injections, mild pain in

51%, moderate pain in 22%, and severe pain in 0% of injections.

Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an

IANB injection. Ninety asymptomatic subjects rated the pain of needle placement with a on a 170-mm Heft-Parker VAS form. No anesthetic was deposited until the target site was reached. Subjects reported none-to-mild pain in 51% of needle placements, and moderate-to-severe pain in 49% of needle placements. The mean VAS score was 54.3 mm, which is in the moderate pain range.

Mikesell (59) evaluated the anesthetic efficacy of articaine and lidocaine for

IANB injections. Fifty-seven asymptomatic subjects recorded the pain of needle placement during the IANB injection on a 170-mm Heft-Parker VAS form. While advancing the needle, 0.2 mL of the anesthetic solution was deposited. Using 2%

20 lidocaine with 1:100,000 epinephrine, no pain during needle placement was reported in

0% of injections, mild pain in 40.4%, moderate pain in 54.4%, and severe pain in 5.3% of injections. The mean VAS score was 60.6 mm, which was in the moderate pain range.

Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for

IAN blocks. Fifty-two asymptomatic subjects recorded the pain of needle placement during the IANB injection on a 170-mm Heft-Parker VAS form. While advancing the needle, 0.2 mL of the anesthetic solution was deposited. Using 2% lidocaine with

1:100,000 epinephrine, no pain during needle placement was reported in 7% of injections, mild pain in 64%, moderate pain in 24%, and severe pain in 5% of injections.

The mean VAS score was 47.5 mm, which was in the mild pain range.

Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine versus a non-buffered solution for IANB injections. While advancing the needle to the target site, 0.2 mL of the solution was deposited. Subjects were asked to rate the discomfort of needle placement on a 4-point scale (0= no pain, 1= mild, 2= moderate, 3= severe). No pain from needle placement was reported by 28% of subjects, while mild pain was reported by 50%, moderate pain by 20%, and severe pain by 2%.

Wolf (57) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with

1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in

IANB injections. Forty asymptomatic subjects rated the pain of needle placement on a 4- point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). As the needle

21

was advanced to the target site, 0.2 mL of anesthetic solution was deposited. Regarding

the lidocaine solution, no pain to needle placement was reported in 30% of injections,

mild pain in 52.5%, moderate pain in 17.5%, and severe pain in 0% of injections.

Regarding the 2.84 mL lidocaine plus mannitol solution, no pain to needle placement was

reported by 30% of subjects, mild pain by 50%, moderate pain by 20%, and severe pain

by 0%. Regarding the 5 mL lidocaine plus mannitol solution, no pain was reported by

22.5% of subjects, mild pain by 50%, moderate pain by 25%, and severe pain by 2.5% of

subjects. There were no significant differences in needle placement pain between the

three solutions.

Nusstein and coauthors (68) evaluated the effects of a 2-stage injection technique on IANB injection pain. Fifty-one asymptomatic subjects were each given an injection of

2.2 mL of 2% lidocaine with 1:100,000 epinephrine at two separate appointments in a

crossover design. A traditional one-stage IANB injection was given with 0.4 mL of anesthetic deposited over 10 seconds during needle placement, and the remaining 1.8 mL of solution deposited at target site over 1 minute. A 2-stage IANB injection was given with 0.4 mL of anesthetic deposited over 1 minute after initial penetration of 2-3 mm.

After waiting 5 minutes, the needle was then reinserted and the remaining 1.8 mL of solution was deposited at the target site over 1 minute. Subjects were asked to rate the pain of needle placement on a 170-mm Heft-Parker VAS. Needle placement pain for the one-stage injection was reported as no pain by 0% of subjects, mild pain by 64.7%, moderate pain by 33.3%, and severe pain by 2% of subjects. The mean VAS score for the one-stage injection was 53 mm, which was in the mild range. Needle placement pain for

22

the two-stage injection was reported as no pain by 27.5% of subjects, mild pain by 51%,

moderate pain by 21.6%, and severe pain by 0% of subjects. The mean VAS score for the

two-stage injection was 33 mm, which was in the mild range. No significant difference

was noted between techniques, except needle placement for women was rated as

significantly less painful with the 2-stage technique.

Pain during needle placement is reported as none-to-mild by a majority of patients

receiving the IANB injection. It appears that this stage of injection is slightly more

painful than needle insertion. A two-stage injection technique resulted in significantly less needle placement pain for women (68); however, injecting a small amount of anesthetic during needle placement did not result in a less painful injection (55, 57, 59,

60). Elmore (62) evaluated the effect of gender on reported pain during needle placement in his study and found no difference. One potential confounding factor appears to be the operator- the person giving the injection. If all variables in the above-listed studies are controlled (ex- needle size, injection type, injection technique, etc.) operator appears to have a large impact; that is, some operators appear to have caused more moderate-to- severe pain during needle insertion than others. Further research needs to be conducted to look at this aspect.

SOLUTION DEPOSITION

Several factors could affect the pain reported with anesthetic solution deposition for the IANB injection. These include the speed of the solution deposition, the type of anesthetic utilized, the volume of anesthetic injected, the presence or absence of a

23

vasoconstrictor, the scale used to record pain, any alterations or additives to the solution,

and even the gender of the subject. In reviewing the literature for data on this subject, one

must take all of these factors into consideration when attempting to compare results

between studies.

Vreeland and coauthors (63) evaluated the anesthetic efficacy of different

volumes and concentrations of lidocaine in the IAN block. Thirty asymptomatic subjects

each received an IANB injections of A: 1.8 mL of 2% lidocaine with 1:100,000

epinephrine, B: 3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and C: 1.8 mL of

4% lidocaine with 1:100,000 epinephrine at 3 separate appointments. The entire

anesthetic solution was deposited over 2 minutes, regardless of volume. Each subject was

asked to rate the pain of injection of the solution on a three-point scale (1= none-to-mild

pain, 2= moderate pain, 3= severe pain). Regarding Solution A, 66.7% of subjects

reported no to mild pain, 26.7% reported moderate pain, and 6.7% reported severe pain.

Regarding Solution B, 63.3% of subjects reported none-to-mild pain, 30% reported moderate pain, and 6.7% reported severe pain. Regarding Solution C, 60% of subjects reported none-to-mild pain, 33.3% reported moderate pain, and 6.7% reported severe

pain. The authors concluded that there were no significant differences in pain of solution

deposition between any of the three anesthetic solutions.

Hinkley (64) evaluated anesthetic efficacy of 4% prilocaine with 1:200,000

epinephrine, 2% mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with

1:100,000 epinephrine for the IAN block. Thirty asymptomatic subjects were given an

IANB injection with 1.8 mL of one of the anesthetic solutions at a rate of 1 mL per

24

minute at each appointment. Subjects recorded the pain of solution injection on a four-

point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). With the

prilocaine solution, no pain was reported by 46.7% of subjects, mild pain by 43.3%,

moderate pain by 10%, and severe pain by 0% of subjects. With the mepivacaine

solution, no pain was reported by 46.7% of subjects, mild pain by 40%, moderate pain by

13.3%, and severe pain by 0% of subjects. With the lidocaine solution, no pain was

reported by 56.7% of subjects, mild pain by 33.3%, moderate pain by 10%, and severe

pain by 0% of subjects. There were no significant differences in pain of solution

deposition found between the three solutions.

Nist and coauthors (69) evaluated the anesthetic efficacy of the incisive nerve

(IN) block and combination IANB/IN blocks. An IANB injection of 3.6 mL of 2%

lidocaine with 1:100,000 epinephrine was given over 2 minutes. Forty subjects recorded

the pain of solution injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 19% of subjects, 56% reported mild pain, 23% reported moderate pain, and 2% reported severe pain.

McLean (65) evaluated the efficacy of prilocaine, mepivacaine, and lidocaine solutions for the IAN block. Thirty asymptomatic subjects were given IANB injections of

1.8 mL of 4% prilocaine plain, 3% mepivacaine plain, and 2% lidocaine with 1:100,000 epinephrine at three successive appointments. The anesthetic solution was given at a rate of 1 mL per minute. Thirty subjects recorded the pain of solution injection on a four-point

scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). With the prilocaine

solution, no pain was reported by 43.4% of subjects, mild pain by 30%, moderate pain by

25

23.3%, and severe pain by 3.3% of subjects. With the mepivacaine solution, no pain was

reported by 33.3% of subjects, mild pain by 40%, moderate pain by 20%, and severe pain

by 6.7% of subjects. With the lidocaine solution, no pain was reported by 33.3% of

subjects, mild pain by 36.7%, moderate pain by 20%, and severe pain by 10% of subjects.

There were no significant differences in the pain of injection for the three solutions.

Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL) injection after an IAN block. For each IANB injection, 1.8 mL of 2% lidocaine with

1:100,000 epinephrine was deposited over a period of 2 minutes. Forty asymptomatic subjects recorded the pain of solution deposition on a four-point scale (0= no pain, 1=

mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 35% of subjects,

mild pain by 47.5%, moderate pain by 17.5%, and severe pain by 0% of subjects.

Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection after an

IAN block. Forty asymptomatic subjects were given an IANB injection with 1.8 mL of

2% lidocaine with 1:100,000 epinephrine over a period of 2 minutes. Subjects were asked

to record the pain of solution deposition on a four-point scale (0= no pain, 1= mild pain,

2= moderate pain, 3= severe pain). No pain was reported in 34% of injections, mild pain

in 45%, moderate pain in 21%, and severe pain in 0% of subjects.

Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following

an IANB injection. For each IANB injection, 1.8 mL of 2% lidocaine with 1:100,000

epinephrine was deposited over one minute. Thirty-eight asymptomatic subjects recorded pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate

26 pain, 3= severe pain). No pain during solution deposition was reported in 82% of injections, mild pain in 17%, moderate pain in 1%, and severe pain in 0% of injections.

Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block and the combination IANB/MN block. Each IANB injection was given with 3.6 mL of

2% lidocaine with 1:100,000 epinephrine deposited over a period of 2 minutes. Thirty asymptomatic subjects recorded pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 17% of subjects, mild pain by 41%, moderate pain by 27%, and severe pain by 15% of subjects.

Yonchak (66) studied the anesthetic efficacy of unilateral and bilateral IAN blocks to determine cross innervation in anterior teeth. Forty asymptomatic subjects were given an IANB injection with 3.6 mL of 2% lidocaine with 1:100,000 epinephrine, which was deposited over 2 minutes. Subjects were asked to record the pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 39.2% of subjects, mild pain by 54.2%, moderate pain by

7.5%, and severe pain by 0% of subjects.

Mikesell (59) evaluated the anesthetic efficacy of 2% lidocaine with 1:100,000 epinephrine and 4% articaine with 1:100,000 epinephrine for IAN blocks. Each IANB injection used 1.8 mL of anesthetic solution and was given over a period of 1 minute.

Immediately following the injection, subjects rated the pain of solution deposition on a

170-mm Heft-Parker VAS form. Regarding the lidocaine solution, no pain was reported by 9% of subjects, mild pain by 72%, moderate pain by 18%, and severe pain by 2% of subjects. The mean VAS score with lidocaine was 31.5 mm, which was in the mild range.

27

Regarding the articaine solution, no pain was reported by 12% of subjects, mild pain by

54%, moderate pain by 30%, and severe pain by 4%. The mean VAS score with articaine

was 39.1 mm, which was in the mild range. There were no significant differences in pain

from solution deposition between the two anesthetics.

Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for

IAN blocks. Fifty-two asymptomatic subjects randomly received an IANB injection of

either 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 3.6 mL of 2% lidocaine

with 1:100,000 epinephrine plus 36 mg of meperidine at two separate appointments. The

anesthetic solution was deposited over 2 minutes regardless of volume. Immediately

following the injection, each subject rated the pain for solution deposition on a 170-mm

Heft-Parker VAS form. Regarding the lidocaine solution, no pain was rated by 8% of

subjects, mild pain by 75%, moderate pain by 12%, and severe pain by 6% of subjects.

The mean VAS score with lidocaine was 40.3 mm, which was in the mild range.

Regarding the lidocaine/meperidine solution, no pain was rated by 4% of subjects, mild

pain by 60%, moderate pain by 25%, and severe pain by 12% of subjects. The mean VAS

score with the lidocaine/meperidine combination was 55.4 mm, which was in the

moderate range. The pain of solution deposition for lidocaine was significantly less than

that of the lidocaine/meperidine combination injection.

Kanaa and coauthors (70) evaluated the influence of the speed of injection on anesthetic efficacy of the IAN block. Thirty-eight asymptomatic subjects received IANB injections of 2 mL 2% lidocaine with 1:80,000 epinephrine at two separate appointments.

The subjects were randomly assigned to groups in which a fast injection was deposited

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over 15 seconds, and a slow injection was deposited over 60 seconds. Subjects were

asked to record the pain of local anesthetic deposition on a 100-mm VAS form.

Regarding the slow injection, discomfort ranged from 0-65 mm with a mean of 20.9 mm.

During the fast injection, reported pain ranged from 3-73 mm with a mean of 30.5 mm.

The fast injection was determined to be significantly more painful to subjects.

Steinkruger (61) evaluated the significance of needle bevel orientation in achieving a successful IAN block. Fifty-one asymptomatic subjects each received an

IANB injection with 2.2 mL of 2% lidocaine with 1:100,000 epinephrine. During the one-stage injection, the clinician injected 0.4 mL of anesthetic over a 10-second period while advancing the needle, then deposited the remaining 1.8 mL of anesthetic over one minute. Subjects rated no pain in 15.7% of injections, mild pain in 68.6%, moderate pain in 15.7%, and severe pain in 0% of one-stage injections. The mean VAS score for the one-stage injection was 33 mm, which was in the mild range. During the two-stage injection, 0.4 mL of anesthetic was deposited over one minute after initial penetration of

2-3 mm. After waiting 5 minutes, the needle was then reinserted and the remaining 1.8 mL of solution was deposited at the target site over one minute. Subjects rated no pain in

15.7% of injections, mild pain in 70.6%, moderate pain in 13.7%, and severe pain in 0% of two-stage injections. The mean VAS score for the two-stage injection was 35 mm,

which was in the mild range. No significant differences in solution deposition pain were

found between the two groups.

Goldberg and coauthors (67) compared the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques for mandibular

29

anesthesia. Forty asymptomatic subjects were injected with 3.6 mL of 2% lidocaine with

1:100,000 epinephrine over a period of 2 minutes. Immediately after the nerve block,

each subject rated the pain for solution deposition of the anesthetic on a 4-point scale (0=

no pain, 1= mild pain, 2= moderate pain, 3= severe pain). Solution deposition for the

IANB was rated as no pain in 38%, mild pain in 48%, moderate pain in 15%, and severe

pain in 0% of injections.

Willett (54) studied the anesthetic efficacy of diphenhydramine and the

combination diphenhydramine/lidocaine for the IAN block. Thirty asymptomatic subjects

were each given 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, 1.8 mL of 1%

diphenhydramine with 1:100,000 epinephrine, and 3.6 mL of a combination of 1.8 mL of

2% lidocaine with 1:100,000 epinephrine and 1.8 mL of 1% diphenhydramine with

1:100,000 epinephrine at three separate appointments in a double-blind, crossover design.

Each IANB injection was deposited at a rate of 1.8 mL per minute. Subjects were asked to rate the pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). Regarding the lidocaine solution, no pain was reported by

24%, mild pain by 40%, moderate pain by 32%, and severe pain by 4% of subjects.

Regarding the diphenhydramine solution, no pain was reported by 0% of subjects, mild pain by 10%, moderate pain by 40%, and severe pain by 50% of subjects. Regarding the lidocaine/diphenhydramine combination solution, no pain was reported by 16% of subjects, mild pain by 28%, moderate pain by 40%, and severe pain by 16% of subjects.

The authors concluded that although deposition of the diphenhydramine solution was

30

significantly more painful, there was no significant difference between the lidocaine

solution and the lidocaine/diphenhydramine combination solution.

A review of medical literature by Davies (71) found that buffering local anesthetics with sodium bicarbonate significantly reduced injection pain. However, the usefulness of this technique in dentistry has been debated. Only a few studies have evaluated the effects of a buffered anesthetic solution on the deposition pain of IAN blocks.

Whitcomb and coauthors (55) evaluated the anesthetic efficacy of 0.17 mEq/mL sodium bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine verses a non- buffered solution for IANB injections. At two separate appointments, 3.6 mL of one of the solutions was deposited at the target site over 2 minutes. Forty asymptomatic subjects were asked to rate the discomfort of solution deposition on a 4-point scale (0= no pain,

1= mild, 2= moderate, 3= severe). The pH of the non-buffered solution was reported as

6.4, while the buffered solution had a pH of 7.5. Regarding the non-buffered lidocaine solution, no pain to solution deposition was reported by 58% of subjects, mild pain by

35%, moderate pain by 8%, and severe pain by 0% of subjects. With the buffered solution, no pain was reported by 72% of subjects, mild pain by 25%, moderate pain by

2%, and severe pain by 0% of subjects. There was no significant difference in pain between the buffered and non-buffered solutions.

Kashyap and coauthors (72) evaluated the effect of alkalinization of lidocaine on the pain of injection during intraoral block injections. One hundred healthy subjects were given IANB, lingual nerve, and long buccal nerve blocks with a maximum of 2.5 mL of

31

anesthetic solutions. The control group received 2% lidocaine with 1:80,000 epinephrine,

and the study group received the same lidocaine solution with a 1/10 dilution of 8.4%

sodium bicarbonate. Pain during injection was assessed on a 4-point scale (0 = no pain, 1

= mild pain, 2 = moderate pain, 3 = severe pain), and was defined as pain that was

described by the patient during injection of the solution. The pH of the lidocaine solution

was measured to be 3.05, and the pH of the buffered lidocaine solution was 7.38. Of the

50 subjects in the control group, 11 reported no pain, 31 reported mild pain, 8 reported

moderate pain, and 0 reported severe pain during the injection. All patients in the study group reported no pain. The authors concluded that buffering an anesthetic solution is effective in reducing the pain of injection.

Ridenour and coauthors (73) evaluated the combination of hyaluronidase and buffered lidocaine with epinephrine in IAN blocks. The control group received an IANB injection of a 1.8 mL solution containing 24 mg lidocaine and 12 µg epinephrine buffered with 0.33 mEq/mL sodium bicarbonate deposited over one minute. Subjects were asked

to rate the pain of solution deposition on a 4-point scale (0 = no pain, 1 = mild pain, 2 =

moderate pain, 3 = severe pain). Subjects reported no pain to solution deposition in 27%

of injections, mild pain in 53%, moderate pain in 13%, and severe pain in 7% of

injections.

Wolf (57) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with

1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M

mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in

IANB injections. Forty asymptomatic subjects rated the pain of solution deposition on a

32

4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). The

anesthetic was deposited over one minute, regardless of volume. Regarding the lidocaine

solution, no pain to solution deposition was reported in 17% of injections, mild pain in

50%, moderate pain in 30%, and severe pain in 3% of injections. Regarding the 2.84 mL

lidocaine plus mannitol solution, no pain to solution deposition was reported by 12% of

subjects, mild pain by 45%, moderate pain by 40%, and severe pain by 3%. Regarding

the 5 mL lidocaine plus mannitol solution, no pain to solution deposition was reported by

7% of subjects, mild pain by 55%, moderate pain by 35%, and severe pain by 3% of

subjects. There were no significant differences in solution deposition pain between the

three solutions.

Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an

IANB injection. Ninety asymptomatic subjects received IANB injections with 1.8 mL of

2% lidocaine with 1:100,000 epinephrine deposited over one minute. Subjects were asked

to rate the pain of solution deposition on a 170-mm Heft-Parker VAS form. The mean

VAS rating was 55.9 mm which was in the moderate range. Subjects reported none-to- mild pain in 48% of injections, and moderate-to-severe pain in 52% of injections.

Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous injection following an IANB injection. Forty asymptomatic subjects were given an IANB injection of 1.8 mL of 3% mepivacaine deposited over one minute. Forty asymptomatic subjects were asked to rate the discomfort of solution deposition during the IANB injection on a 4-point scale (0= no pain, 1= mild, 2= moderate, 3= severe). No pain was

33

reported by 58% of subjects, mild pain by 35%, moderate pain by 6%, and severe pain by

2% of subjects.

Kramp and coauthors (48) evaluated prilocaine for the reduction of pain associated with the intraoral administration of local anesthesia. This study compared 2% mepivacaine with 1:20,000 levonordefrin, 2% lidocaine with 1:100,000 epinephrine, and

4% prilocaine plain in asymptomatic patients. No topical anesthetic was used. A 1.8 mL solution was injected with a 30-gauge needle for the IANB injection in 36 subjects.

Following the injection, each patient was asked to describe the level of discomfort associated with the injection by marking the appropriate number on a 10-point VAS form. The phases of injection were not separated in this study. Mean scores for each solution were as follows: mepivacaine = 3.0, lidocaine = 2.6 and prilocaine = 2.0. The authors concluded that the injection of prilocaine resulted in significantly less pain, with no difference between lidocaine and mepivacaine. They hypothesize that this difference is due to the pH of the anesthetic solutions, which were recorded as follows: lidocaine =

4.12; mepivacaine = 3.05; prilocaine = 6.28.

Wahl, Schmitt, and Overton (74) evaluated injection pain of 4% prilocaine plain,

3% mepivacaine plain, 4% articaine with 1:100,000 epinephrine, and 2% lidocaine with

1:100,000 epinephrine in patients undergoing routine dental procedures. Topical anesthetic (Benzo-Jel) was placed at the injection site for 10 seconds. A 25-gauge needle was used to given an IANB injection of 1.8 mL of anesthetic. Subjects were asked to rate the pain of injection on a ten point scale where 1 = no pain and 10 = unbearable pain. The phases of injection were not separated in this study. For the IANB, 609 subjects reported

34 the following mean pain scores: articaine = 3.33, lidocaine = 3.14, mepivacaine = 3.12 and prilocaine = 2.66. Authors concluded that prilocaine was significantly less painful, and hypothesized that this may be associated with the higher pH of the solution. The pHs of the anesthetic solutions as measured by the authors were recorded as follows: prilocaine = 5.5-6.5; lidocaine = 4.0-4.5; articaine = 3.5-4.5; mepivacaine = 4.5-5.5.

Wahl and coauthors (49) evaluated pain of injection between 4% prilocaine plain and 2% lidocaine with 1:100,000 epinephrine in patients undergoing routine dental procedures. Topical anesthetic (20% benzocaine) was placed at the injection site for an unspecified amount of time preceding the injection. A 25-gauge needle was used to give an IANB injection of 1.8 mL of anesthetic solution. Immediately following the injection,

145 patients were asked to rate the pain of injection on a 6-point scale (0= no pain, 1= mild, 2= moderate, 3= distressing, 4= horrible, 5= unbearable). The phases of injection were not separated in this study. Mean scores for the IANB injections were 0.63 for prilocaine, and 0.72 for the lidocaine solution. No significant difference was found between the two solutions.

Sumer et al. (75) compared the injection pain of 4% articaine with 1:200,000 epinephrine, 3% prilocaine with 1.08 µg phenylpressin, and 2% lidocaine with 1:100,000 epinephrine. Three hundred eighteen asymptomatic subjects received an IANB injection with one of the three solutions. Topical anesthetic was applied to the injection site for 5 to 10 seconds, and an unspecified amount of anesthetic was injected slowly (time not specified). Subjects who received more than one injection were excluded from the study.

Immediately after the injection, subjects were asked to rate their injection pain on a 6-

35

point scale (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = distressing pain, 4 =

horrible pain, 5 = unbearable pain). The phases of injection were not separated in this

study. Subjects reported none-to-mild pain for 75.4% of injections. The authors

concluded that there were no significant differences among the anesthetic solutions for

injection pain, although the results were not analyzed by location of injection.

Kanaa and coauthors (76) gave subjects an IANB injection of 2 mL of 2% lidocaine with 1:80,000 epinephrine over one minute at each appointment. Immediately after needle withdrawal, subjects were asked to rate the discomfort associated with the injection on a 100 mm visual analogue scale (VAS). The phases of injection were not separated in this study. VAS scores for the IANB injection with lidocaine ranged from 7-

81 mm, with a mean of 32.2 mm and 34.7 mm at each appointment.

In the studies reviewed, subjects reported moderate-to-severe pain during solution deposition in approximately 24% of injections. While it has been hypothesized that the injection of an anesthetic solution with a higher pH (due to anesthetic selection or buffering) is less painful, there is currently not enough evidence to support this theory.

Giving an injection slowly; however, does seem to be less painful than a fast injection

(70). The effect of gender was analyzed in one study, and no significant difference was found in terms of pain reported during solution deposition (62).

SUMMARY OF INJECTION PAIN

Although the scales used to measure pain in these studies differed (VAS vs. ordinal scale), Kreimer (77) showed a high correlation between subject responses using a

36

4-point scale and a 170-mm Heft-Parker VAS. Overall, subjects rated the least pain

during needle insertion, but ¼ to 1/3 of subjects reported moderate-to-severe pain during needle placement and solution deposition. In the studies that didn’t separate the phases of needle insertion and needle placement, reported pain levels were similar to needle placement values of the studies that analyzed needle placement individually. No difference in pain has been reported regarding gender with the conventional IANB injection, although a two-stage technique resulted in significantly less pain during needle placement in females (68). Further evaluation or research may be warranted to look into the gender effect.

ANESTHETIC SUCCESS RATES

The traditional method for determining the success of the IANB is lip numbness, which usually occurs within 4.5 to 6 minutes of injection (16, 63, 78, 79). Studies confirm that although this clinical sign determines that the injection has been given accurately, pulpal anesthesia may not have been obtained (1, 16, 55, 56, 62, 63, 67, 69,

70, 73, 76, 78-99). The onset of pulpal anesthesia, which can be defined as two consecutive 80/80 readings on an electric pulp tester, generally occurs within 5-19 minutes of local anesthetic administration (16, 63, 67, 78, 79, 89, 91). Successful mandibular pulpal anesthesia, which has been defined in some studies as pulp numb within fifteen minutes and continuously numb for one hour, tends to be more frequent in molars (32-92%) and premolars (38-92%) than in incisors (2-67%) (1, 16, 55, 56, 62, 63,

67, 69, 70, 73, 76, 78-99). Although there is an abundance of information on anesthetic

37

success, this section will focus solely on studies looking at the success rates of 2%

lidocaine with 1:100,000 epinephrine and 3% mepivacaine with the IAN block.

LIDOCAINE

Vreeland and coauthors (63) evaluated the anesthetic efficacy of different

volumes and concentrations of lidocaine with the IAN block. Thirty asymptomatic

subjects each received IANB injections of A: 1.8 mL of 2% lidocaine with 1:100,000

epinephrine, B: 3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and C: 1.8 mL 4%

lidocaine with 1:100,000 epinephrine at three separate appointments. The first molar,

canine, lateral incisor, and contralateral canine (control) were tested with an electric pulp

tester (EPT) every 3 minutes for 55 minutes. Anesthesia was considered to be successful

if an 80 reading was obtained within 16 minutes of injection and continuously sustained

for the remainder of the testing period. Successful anesthesia using Solution A occurred

in 63.3% of first molars, and in 33.3% of lateral incisors. With solution B, success

occurred in 63.3% of first molars and 43.3% of lateral incisors. With solution C, success

occurred in 53.3% of first molars and 43.3% of lateral incisors. The authors concluded

that there were no significant differences in successful pulpal anesthesia between the

solutions.

Hinkley et al. (78) evaluated 4% prilocaine with 1:200,000 epinephrine, 2% mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with 1:100,000 epinephrine for the IAN block. Thirty asymptomatic subjects were given an IANB injection with 1.8 mL of one of the anesthetic solutions at each appointment. The first molar, first premolar,

38

lateral incisor, and contralateral canine (control) were then tested with an EPT every 3

minutes for 50 minutes. Anesthesia was considered to be successful if an 80 reading was

achieved within 16 minutes of injection and sustained for the remainder of the 50-minute test period. Anesthetic success with lidocaine was 54% in the first molar, 50% in the first premolar, and 36% in the lateral incisor. Anesthetic success with mepivacaine was 57% in the first molar, 54% in the first premolar, and 36% in the lateral incisor. There were no significant differences in anesthetic success found between any of the solutions.

Chaney and coauthors (79) evaluated lidocaine hydrocarbonate compared with lidocaine hydrochloride for IAN blocks. Thirty asymptomatic subjects received 1.8 mL injections of 2.2% lidocaine hydrocarbonate, 2.2% lidocaine hydrocarbonate with

1:100,000 epinephrine, and 2% lidocaine with 1:100,000 epinephrine at three separate appointments. The first molar, first premolar, and lateral incisor were tested with an EPT

every 3 minutes for 60 minutes. Anesthesia was considered successful when an 80

reading was obtained within 16 minutes of injection and sustained for the remainder of

the test period. Anesthetic success with 2% lidocaine with 1:100,000 epinephrine was

seen in 57% of first molars, 63% of first premolars, and 43% of lateral incisors.

Nist and coauthors (69) studied the combination of the inferior alveolar nerve and

incisive nerve blocks in mandibular anesthesia. Forty asymptomatic subjects with vital

teeth were given an IANB injection with 3.6 mL of 2% lidocaine with 1:100,000

epinephrine. The first and second molars, first and second premolars, central and lateral

incisors, and contralateral canine (control) were then tested with an EPT every 4 minutes

for 60 minutes. Anesthesia was considered to be successful when an 80 reading was

39 obtained within 15 minutes of injection and sustained for 60 minutes. Anesthetic success of the IANB alone was 15% in the central incisor, 35% in the lateral incisor, 70% in the first premolar, 52% in the second premolar, 43% in the first molar, and 50% in the second molar.

McLean et al. (16) evaluated the efficacy of 4% prilocaine, 3% mepivacaine, and

2% lidocaine solutions for the IAN block. Thirty asymptomatic subjects were given

IANB injections of 1.8 mL of 4% prilocaine, 3% mepivacaine, and 2% lidocaine with

1:100,000 epinephrine at three successive appointments. Following the injection, the first molar, first premolar, lateral incisor, and contralateral canine (control) were tested with an EPT every 3 minutes for 50 minutes. Anesthesia was considered successful if an 80 reading was achieved within 16 minutes of injection and sustained for the remainder of the 50 minutes of the test. Anesthetic success with lidocaine was 63% in the first molar,

67% in the first premolar, and 30% in the lateral incisor. Anesthetic success with mepivacaine was 43% in the first molar, 57% in the first premolar, and 30% in the lateral incisor. There were no statistically significant differences found between any of the three anesthetic solutions.

Childers and coauthors (80) studied the anesthetic efficacy of the periodontal ligament (PDL) injection after an IAN block. Forty asymptomatic subjects received an

IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, second premolar, and contralateral canine (control) were tested with an

EPT every 2 minutes for 60 minutes. Anesthesia was considered successful when an 80 reading was obtained within 15 minutes and sustained for the remainder of the test

40 period. Anesthetic success of the IANB alone was 63% in the first molar, 73% in the second molar, and 60% in the second premolar.

Dunbar and coauthors (81) evaluated the anesthetic efficacy of the intraosseous injection after an IANB injection. Forty asymptomatic subjects were given an IANB injection with 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, the second premolar, and the contralateral canine (control) were tested with an

EPT every 2 minutes for 60 minutes. Anesthesia was considered successful when an 80 reading was obtained within 15 minutes, and sustained for the remainder of the test period. Anesthetic success of the IANB alone was 42% in the first molar, 45% in the second molar, and 38% in the second premolar.

Dagher and coauthors (82) evaluated 2% lidocaine with different concentrations of epinephrine for the IAN block. Thirty asymptomatic subjects were each given three

IANB injections at successive appointments: 1.8 mL of 2% lidocaine with 1:50,000 epinephrine, 1.8 mL 2% lidocaine with 1:80,000 epinephrine, and 1.8 mL 2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor, and contralateral canine (control) were tested with an EPT every 3 minutes for 50 minutes.

Anesthesia was considered successful if an 80 reading was achieved within 16 minutes and sustained for the remainder of the 50-minute test period. Anesthetic success with the

1:100,000 epinephrine formulation was 47% in the first molar, 43% in the first premolar, and 50% in the lateral incisor. The authors concluded that anesthetic success was not significantly different among the three solutions.

41

Yared and Dagher (83) evaluated lidocaine with different concentrations of

epinephrine with larger volumes of anesthetic for the IAN block. Thirty asymptomatic

subjects were each given 3.6 mL of 2% lidocaine with 1:50,000 epinephrine, 3.6 mL of

2% lidocaine with 1:80,000 epinephrine, and 3.6 mL of 2% lidocaine with 1:100,000

epinephrine at three separate appointments in a double-blind, repeated measures design.

The first molar, first premolar, lateral incisor, and contralateral canine (control) were

tested with an EPT every 3 minutes for 50 minutes. Anesthesia was considered successful

if an 80 reading was obtained within 16 minutes and sustained for the remainder of the

50-minute testing period. Anesthetic success with 2% lidocaine with 1:100,000

epinephrine was 77% for the first molar, 80% for the first premolar, and 67% for the

lateral incisor. The authors concluded that the concentration of epinephrine did not

influence the degree of pulpal anesthesia when utilizing 3.6 mL of anesthetic.

Reitz and co-authors (84) studied the augmentation of an IAN block with an

intraosseous injection of 0.9 mL of 2% lidocaine with 1:100,000 epinephrine. Thirty-

eight asymptomatic subjects with vital teeth were given an IANB injection with 1.8 mL

of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, the second

premolar and the contralateral canine (control) were then tested with an EPT every 2

minutes for 120 minutes. Anesthesia was considered successful when 2 consecutive 80

readings were obtained. Percentages of anesthetic success for the IANB alone were 60%

in the second premolar, 71% in the first molar, and 74% in the second molar.

Clark and coauthors (85) evaluated the anesthetic efficacy of the mylohyoid nerve

(MN) block and the combination IANB/MN block. Each IANB consisted of 3.6 mL of

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2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second

premolars, central and lateral incisors, and contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were recorded. Anesthetic success for the IANB was 87% in the second molar, 73% in the first molar, 90% in the second premolar, 87% in the first

premolar, 50% in the lateral incisor, and 33% in the central incisor.

Hannan and coauthors (86) evaluated the use of ultrasound for guiding needle

placement for IAN blocks. Forty asymptomatic subjects received an ultrasound-assisted

IANB and a conventional IANB at 2 separate appointments. For each injection, 1.8 mL

of 2% lidocaine with 1:100,000 epinephrine was deposited. The first and second molars,

first and second premolars, central and lateral incisors, and contralateral canine (control)

were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered

successful when 2 consecutive 80 readings were obtained. Anesthetic success with the

ultrasound IANB was 92% in the second molar, 78% in the first molar, 92% in the

second premolar, 88% in the first premolar, 65% in the lateral incisor, and 38% in the

central incisor. Anesthetic success with the conventional IANB was 92% in the second

molar, 85% in the first molar, 90% in the second premolar, 90% in the first premolar,

65% in the lateral incisor, and 38% in the central incisor. The authors concluded that

there were no significant differences in anesthetic success between the two techniques.

Yonchak and coauthors (87) studied the anesthetic efficacy of unilateral and

bilateral IAN blocks to determine cross innervation in anterior teeth. Forty asymptomatic

subjects with vital teeth were given a unilateral IANB injection with 3.6 mL of 2%

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lidocaine with 1:100,000 epinephrine. The ipsilateral lateral incisor, central incisor, and

canine, were then tested with an EPT every 4 minutes for 60 minutes. Anesthesia was

considered successful when 2 consecutive 80 readings were obtained. Success rates of the

unilateral IANB were 39% in the central incisor, 50% in the lateral incisor, and 68% in

the canine.

Mikesell and coauthors (88) compared the anesthetic efficacy of articaine and

lidocaine for IAN blocks. Fifty-seven asymptomatic subjects were given 1.8 mL of 2%

lidocaine with 1:100,000 epinephrine. The first and second molars, first and second

premolars, central and lateral incisors, and contralateral canine (control) were then tested

with an EPT every 4 minutes for 60 minutes. Anesthesia was considered to be successful

when 2 consecutive 80 readings were obtained within 15 minutes and continuously

sustained for 60 minutes. Anesthetic success with lidocaine was 48% in the second

molar, 32% in the first molar, 29% in the second premolar, 42% in the first premolar,

14% in the lateral incisor, and 2% in the central incisor.

Fernandez et al. (89) compared the anesthetic efficacy of and

lidocaine for IAN blocks. Thirty-nine asymptomatic subjects were given an IAN block injection with 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second premolars, lateral incisor, and contralateral canine (control) were then tested with an Analytic Technology pulp tester every 3 minutes for the first 2 hours and testing continued for 5 hours or until at least two consecutive readings of less than 80 were recorded on 3 of the 5 experimental teeth. Anesthesia was considered successful if an 80 reading was achieved within 15 minutes and continuously sustained for 60 minutes.

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Anesthetic success with lidocaine was observed in 77% of second molars, 54% of first

molars, 74% of second premolars, 84% of first premolars, and 54% of lateral incisors.

Goodman and coauthors (90) evaluated the anesthetic efficacy of lidocaine and meperidine for IAN blocks. Fifty-two asymptomatic subjects randomly received an

IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second premolars, central and lateral incisors, and contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes and the 80 reading was continuously sustained for 60 minutes. Anesthetic success was

58% in the second molar, 44% in the first molar, 48% in the second premolar, 51% in the first premolar, 23% in the lateral incisor, and 8% in the central incisor.

Kanaa and coauthors (70) evaluated the influence of the speed of injection on anesthetic efficacy of the IAN block. Thirty-eight asymptomatic subjects received IANB injections of 2 mL 2% lidocaine with 1:80,000 epinephrine at two separate appointments, with a fast injection (deposited over 15 seconds), and a slow injection (deposited over 60 seconds). The mandibular first molar, first or second premolar, and lateral incisor were tested with an EPT every 2 minutes for the first 10 minutes following the injection, then every 5 minutes for the remainder of the 55-minute testing period. The anesthetic efficacy was evaluated by comparing the number of 80 readings obtained by all subjects (total pulpal anesthesia) throughout the testing period and separating the results by tooth (532 readings per tooth). Regarding the slow injection; 80 readings were seen in 220 cases for molars, 253 cases for premolars, and 119 cases for lateral incisors. Regarding the fast

45 injection; 80 readings were seen in 159, 216, and 99 cases, respectively. The authors concluded that a slow IANB injection may result in improved anesthetic efficacy in asymptomatic patients.

Steinkruger and coauthors (91) evaluated the significance of needle bevel orientation in achieving a successful IAN block. Fifty-one asymptomatic subjects each received an IANB injection with the needle bevel oriented away from the mandibular ramus and an IANB injection with the needle bevel oriented toward the mandibular ramus at two separate appointments. Each IANB injection was given with 2.2 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second premolars, central and lateral incisors, and contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered to be successful if two consecutive 80 readings were obtained within 15 minutes and continuously sustained for the remainder of the testing period. When the needle bevel was oriented away from the ramus, anesthetic success was found in 90% of second molars, 76% of first molars,

78% of second premolars, 80% of first premolars, 43% of lateral incisors, and 24% of central incisors. When the needle bevel was oriented toward the ramus, anesthetic success was found in 92% of second molars, 73% of first molars, 78% of second premolars, 73% of first premolars, 33% of lateral incisors, and 14% of central incisors. The authors concluded that there were no significant differences between the two needle bevel orientations.

Foster and coauthors (92) studied the anesthetic efficacy of buccal and lingual infiltrations of lidocaine following an IAN block in mandibular posterior teeth. Forty-

46

nine asymptomatic subjects were given an IANB plus mock buccal infiltration and mock

lingual infiltration of the first mandibular molar. Each IANB injection used 3.6 mL of 2%

lidocaine with 1:100,000 epinephrine. The first and second molars, first and second

premolars, and contralateral canine (control) were then tested with an EPT. Anesthesia

was considered successful when 2 consecutive 80 readings were obtained within 15

minutes, and continuously sustained for 60 minutes. Anesthetic success of the IANB

alone was 74% in the second molar, 53% in the first molar, 66% in the second premolar,

and 56% in the first premolar.

Goldberg and coauthors (67) compared the anesthetic efficacy of the conventional

IANB, Gow-Gates, and Vazirani-Akinosi techniques for mandibular anesthesia. Forty asymptomatic subjects were given 3 injections at separate appointments using 3.6 mL of

2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor, and contralateral canine (control) were tested with an EPT every 3 minutes for 60 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes of the injection and the 80 reading was continuously sustained for the remainder of the 60-minute testing period. Anesthetic success for the

IANB was 53% in the first molar, 62% in the first premolar, and 25% in the lateral incisor.

Willett and coauthors (93) studied the anesthetic efficacy of diphenhydramine and the combination diphenhydramine/lidocaine for the IAN block. Thirty asymptomatic subjects were each given 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second premolars, lateral and central incisors, and

47 contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes.

Anesthesia was considered successful when two consecutive 80 readings were obtained within 15 minutes and continuously sustained through the entire testing period.

Anesthetic success with lidocaine alone was 84% for the second molar, 52% for the first molar, 52% for the second premolar, 68% for the first premolar, 36% for the lateral incisor, and 12% for the central incisor.

Kanaa and coauthors (76) studied the buccal infiltration of articaine following an

IANB with lidocaine. Thirty-six asymptomatic subjects were given an IANB injection of

2 mL of 2% lidocaine with 1:80,000 epinephrine. This was followed by either a buccal injection of 4% articaine solution, or a mock buccal injection. The first molar, first premolar (or second premolar if the first premolar was removed for orthodontic treatment), and lateral incisor were tested with an EPT every 2 minutes for 10 minutes, then every 5 minutes for the remainder of the 45 minute testing period. Anesthesia was considered successful if there was no response to maximum stimulation with two or more consecutive readings. Anesthetic success for the IANB alone was 55.6% in the first molar, 66.7% in the premolars, and 19.4% in the lateral incisors.

Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine verses a non-buffered solution for IANB injections. Forty asymptomatic subjects were given 3.6 mL of local anesthetic solution. The first and second molars, first and second premolars, lateral and central incisors, and contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered successful when two consecutive 80

48 readings were obtained within 15 minutes and continuously sustained for the entire testing period. Anesthetic success was seen in 65% of second molars, 58% of first molars, 68% of second premolars, 71% of first premolars, 35% of lateral incisors, and

10% of central incisors.

Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB administered with the aid of a peripheral nerve stimulator. Forty-six asymptomatic patients each received a conventional IANB and an IANB administered utilizing a peripheral nerve stimulator to localize the inferior alveolar nerve at two separate appointments. Each IANB injection was given with 1.8 mL 2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor, and contralateral canine

(control) were tested with an EPT every 2 minutes for 60 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes and continuously sustained for the entire testing period. Anesthetic success of the conventional IANB was found to be 45% in the first molar, 42% in the first premolar, and

32% in the lateral incisor. The authors concluded that there was no significant difference in anesthetic success between the two IANB techniques.

Wali and coauthors (94) evaluated the anesthetic efficacy of 1.8 and 3.6 mL of

2% lidocaine with 1:50,000 epinephrine versus 1.8 mL 2% lidocaine with 1:100,000 epinephrine for the IAN block. Thirty asymptomatic subjects each received an IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor, and contralateral canine (control) were tested with an EPT every

3 minutes for 60 minutes. Anesthesia was considered to be successful when 2 consecutive

49

80 readings were obtained within 15 minutes and continuously sustained for the remainder of the testing period. Successful anesthesia occurred in 43% of first molars,

60% of first premolars, and 40% of lateral incisors.

Hutchison and coauthors (95) evaluated the anesthetic efficacy of frequency- dependent conduction blockade of the inferior alveolar nerve. Eighty asymptomatic subjects randomly received an IANB injection of 1.8 mL 2% lidocaine with 1:100,000 epinephrine at two separate appointments. Subjects then received continuous electrical stimulation or mock electrical stimulation of the first molar or lateral incisor for six cycles of three minutes each. An EPT was used to test the teeth for pulpal anesthesia between stimulation cycles for a total of 64 minutes. Anesthesia was considered to be successful when two consecutive 80 readings were obtained within 15 minutes and the 80 reading was sustained for the remainder of the 64-minute testing period. Regarding the group that received electrical stimulation, anesthetic success was seen in 35% of lateral incisors and 48% of first molars. Regarding the mock-stimulation group, anesthetic success was seen in 18% of lateral incisors and 62% of first molars. The authors concluded that there were no significant differences between the two groups, and that continuous electrical stimulation did not result in greater anesthetic success with the IAN block.

Wolf et al. (96) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with

1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in

IANB injections. Forty asymptomatic subjects each received IANB injections with these

50

anesthetic solutions. The first and second molars, first and second premolars, and lateral

and central incisors were tested with an EPT every 4 minutes for 60 minutes. Mean total

pulpal anesthesia was defined as the total of all the times of pulpal anesthesia (80

readings) over the 60-minute testing period. Regarding the 1.8 mL solution; mean total pulpal anesthesia was seen in second molars 75% of the time, first molars 48%, second premolars 54%, first premolars 50%, lateral incisors 27%, and central incisors 12% of the time.

MEPIVACAINE

Guglielmo and coauthors (97) evaluated the anesthetic efficacy of a supplemental intraosseous injection following an IANB injection. Forty asymptomatic subjects were given an IANB injection of 1.8 mL of 3% mepivacaine. The first and second molars, second premolar, and contralateral canine (control) were tested with an EPT every 2 minutes for 60 minutes. Anesthesia was considered to be successful when two consecutive 80 readings were obtained. Anesthetic success for the IANB was 80% for the first molar, 90% for the second molar, and 77% for the second premolar.

Gallatin and coauthors (98) evaluated the anesthetic efficacy and heart rate effects

of the intraosseous injection of 3% mepivacaine after an IAN block. Forty-eight asymptomatic subjects were given an IANB injection of 1.8 mL of 3% mepivacaine. The first molar and contralateral canine (control) were tested with an EPT every 2 minutes for

60 minutes. Anesthesia was considered to be successful when two consecutive 80

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readings were obtained. Regarding the IANB + mock IO injections, anesthetic success in

the first molar was 81%.

Stabile and coauthors (99) evaluated the anesthetic efficacy and heart rate effects

of the intraosseous (IO) injection of 1.5% with 1:200,000 epinephrine

following an IAN block. Forty-eight asymptomatic subjects received an IANB injection

of 1.8 mL of 3% mepivacaine. The first molar was tested with an EPT every 2 minutes

for 60 minutes. Anesthesia was considered to be successful when two consecutive 80

readings were obtained. Regarding the IANB + mock IO injections, anesthetic success in

the first molar was 81%.

McLean and coauthors (16) evaluated the efficacy of 4% prilocaine, 3%

mepivacaine, and 2% lidocaine solutions for the IAN block, as previously described.

Anesthetic success with mepivacaine was 43% in the first molar, 57% in the first

premolar, and 30% in the lateral incisor. There were no statistically significant

differences found between any of the three anesthetic solutions.

IMPACT OF VOLUME OF ANESTHETICS ON SUCCESS WITH IANB

Research on the impact of the volume of anesthetic injected for the IANB has been conducted to see if an increase in success can occur when the volume injected increases. Nusstein and coauthors (1) evaluated the anesthetic efficacy of different volumes of lidocaine with epinephrine for IAN blocks. In this retrospective study, four hundred sixty-two asymptomatic subjects were given an IANB injection of either 1.8 mL or 3.6 mL of 2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar,

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lateral incisor, and contralateral canine (control) were tested with an EPT at 3-4 minute cycles for 55-60 minutes. Anesthesia was considered successful when two consecutive 80 readings were obtained within 15-16 minutes and continuously sustained for the entire testing period. Anesthetic success with 1.8 mL occurred in 53% of first molars, 61% of first premolars, and 35% of lateral incisors. Anesthetic success with 3.6 mL occurred in

44% of first molars, 67% of first premolars, and 32% of lateral incisors. The authors concluded that there was no significant difference in successful pulpal anesthesia between the two volumes of anesthetic.

In the study previously mentioned by Vreeland (63), the authors concluded that there were no significant differences in successful pulpal anesthesia between anesthetic solutions, regardless of volume. However, a retrospective evaluation by Yared and

Dagher (83) states a significant difference in the anesthetic success of first molars and first premolars when doubling the volume of the anesthetic solution, independent of epinephrine concentration.

INCIDENCE AND TYPES OF ANESTHETIC FAILURE

Anesthetic failure in asymptomatic patients in a study setting has been defined as

the percentage of patients who never achieve two consecutive 80 EPT readings during a

defined testing period. Clinically, anesthetic failure represents a patient who would feel

pain during a dental procedure. Studies have shown that pulpal anesthetic failure occurs

with the IANB in 17-58% of asymptomatic patients, and has been shown to be even

higher in cases of irreversible pulpitis (1, 4, 15, 16, 63, 69, 78-88). Slow onset of

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anesthesia is a subset of failure that occurs when patients achieve pulpal anesthesia

greater than 15 minutes post-injection. Non-continuous anesthesia is considered to have occurred when the subject achieved two consecutive 80 readings, lost the 80 reading, then regained the 80 reading. Anesthesia of short duration has also been seen when a subject achieved two consecutive 80 readings, but lost the 80 reading before the end of the testing period. These definitions tend to be used when more specific, time-related definitions of anesthetic success are utilized.

A retrospective study by Nusstein et al. (1) reviewed failures by volume of anesthetic. When using 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, anesthetic failure occurred in 17% of first molars, 11% of first premolars, and 32% of lateral incisors. Regarding 3.6 mL of the same solution, anesthetic failure was observed in 21% of first molars, 10% of first premolars, and 39% of lateral incisors. No significant differences were found between the two volumes for any of the types of failure.

REASONS for FAILURE

While the cause of anesthetic failure remains undetermined, there are several hypotheses as to why this phenomenon occurs. Traditionally, it has been assumed that anatomic variation has led to inadequate nerve blockade (100); however, Hannan et al.

(86), Simon et al. (56), and Steinkruger et al. (91) have shown that even an accurate injection can result in failure of pulpal anesthesia. Another theory is that accessory nerve innervation may prevent mandibular pulpal anesthesia when only the inferior alveolar nerve is blocked. The chief nerve that is considered is the mylohyoid nerve which

54

branches from the IAN prior to its entry into the mandibular canal. The mylohyoid nerve

runs downward and along the mylohyoid groove on the medial surface of the ramus (20).

A study by Clark et al. (85) showed no improvement in pulpal anesthesia when adding

the mylohyoid nerve block to the IANB. Also implicated is the retromolar canal, which

may contain accessory innervation to the mandibular teeth. Von Arx et al. (101) recently

showed a 25% incidence of this canal that branches off from the mandibular canal behind

the third molar and travels to the retromolar foramen in the retromolar fossa. Failure and

low success rates in mandibular anterior teeth have been associated with IAN cross-

innervation. Yonchak et al. (87) attempted to achieve pulpal anesthesia in mandibular

anterior teeth utilizing bilateral mandibular blocks, and although this technique was

slightly more successful than a unilateral block, anesthetic failure was still observed in

mandibular incisors.

It has been hypothesized that a lower pH due to inflammation at the site of

injection or solution pH may result in ion trapping as the charged acid form is unable to

cross the cell membrane; however, the actual pH change may not be large enough to

produce substantial ion trapping and with the IANB the site of injection is not inflamed

(100). Buffering an anesthetic with sodium bicarbonate causes CO2 to enter cell and decrease intracellular pH, which favors the passage of the ionized form of an anesthetic to pass through the cell membrane. Whitcomb et al. (55) studied this theory in asymptomatic patients, but no difference was seen in anesthetic success between buffered and non-buffered anesthetics for the IANB injection.

55

Perhaps the most widely accepted theory for anesthetic failure in asymptomatic

patients is the central core theory. This theory states that the fibers on the outside of the

nerve bundle, which are the first to be anesthetized, supply the molars while the fibers in

the center of the nerve bundle, which are the last to be anesthetized, supply the anterior

teeth (15, 24, 102). While this theory may explain higher experimental failure rates in

anterior teeth, it does not address anesthetic failure in molars or premolars (15).

SUMMARY OF SUCCESS - LIDOCAINE VS. MEPIVACAINE

Many studies have evaluated the anesthetic efficacy of 2% lidocaine with

1:100,000 epinephrine for IAN blocks. While this anesthetic has become the standard to which many other anesthetics are compared, success rates range from 32-92% in molars,

38-92% in premolars, and 2-67% in incisors. In the limited studies evaluating 3% mepivacaine plain, success rates range from 43-90% in molars, 54-77% in premolars, and

30-36% in incisors. Although the success rates of these two anesthetic formulations are similar, there remains room for improvement.

Some clinicians combine 3% mepivacaine plain with 2% lidocaine with

1:100,000 epinephrine for IAN blocks. The thought behind this is that 3% mepivacaine has more anesthetic molecules available to block sodium channels due to its higher concentration, and that it also has a higher pH (pH = 6.6) because it does not contain epinephrine. Both of these concepts may provide more of the base form of the anesthetic for the IANB initially, therefore potentiating the anesthetic effect after administration of lidocaine. Rood and coauthors (17) reported on the potential benefits of using prilocaine

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and lidocaine in combination, but it was determined that there was no potentiation of the

anesthetic effect.

Another potential benefit of using mepivacaine is that it may lessen the pain of

injection. Many practitioners feel that the higher pH of the solution, as compared to

lidocaine (pH = 4.2), results in less pain during solution deposition. McLean et al. (16)

showed no difference when comparing pain of solution deposition utilizing 3%

mepivacaine and 2% lidocaine with 1:100,000 epinephrine; however, other studies have

shown that the injection of a solution with a higher pH is less painful (48, 74). Guglielmo and coauthors (97) reported moderate-to-severe pain in only 8% of subjects during solution deposition of 3% mepivacaine.

While studies have shown that 3% mepivacaine was equivalent to 2% lidocaine with 1:100,000 epinephrine for an IAN block (4,16), no clinical trial has evaluated the combination of 3% mepivacaine and 2% lidocaine with 1:100,000 epinephrine for IAN blocks. Therefore, the purpose of this prospective, randomized, double-blind study is to compare the degree of pulpal anesthesia obtained with a combination 3% mepivacaine/2% lidocaine with 1:100,000 epinephrine formulation versus 2% lidocaine with 1:100,000 epinephrine/2% lidocaine with 1:100,000 epinephrine formulation in inferior alveolar nerve blocks, and to study the injection pain of the two sets of IAN blocks.

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MATERIALS AND METHODS

One hundred adult subjects (50 males, 50 females) participated in this study. The

subjects were in good health as determined by a written health history and oral

questioning. Exclusion criteria were as follows: younger than 18 or older than 65 years of

age; ASA Classification of III or greater; allergy to local anesthetics or sulfites; taking

any medications (analgesics, , anti-depressant or anti-anxiety medications) that

would alter perception of pain or metabolism of anesthetics within the last 48 hours;

inability to give informed consent. Females were questioned regarding pregnancy and

were not allowed to participate if pregnant, suspected a pregnancy, trying to become

pregnant, or lactating. If a pregnancy was suspected, female subjects were required to

take a urine pregnancy test (Osom®, Genzyme Diagnostics Corp, San Diego, CA) before

participation in the appointment was allowed. The Ohio State University Human Subjects

Review Committee approved the study and written informed consent was obtained from

each subject. Subjects were also asked to fill out a Health Insurance Portability and

Accountability Act (HIPAA) release form (APPENDIX E).

The 100 blinded subjects randomly received two sets of IAN blocks: either a cartridge of 3% mepivacaine (Carbocaine, Dentsply Pharmaceutical, York, PA) followed by a cartridge of 2% lidocaine with 1:100,000 epinephrine (Xylocaine, Dentsply

Pharmaceutical, York, PA) or a cartridge of 2% lidocaine with 1:100,000 epinephrine

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followed by a second cartridge of 2% lidocaine with 1:100,000 epinephrine, at two separate appointments spaced at least one week apart, in a crossover design. With the crossover design, there were 200 sets of IAN blocks administered and each subject served as his or her own control. An equal number of sets of IAN blocks were administered on the right side and the left side. The same side randomly chosen for the first set of injections was used again for the second set of injections. The test teeth chosen for the experiment were the first and second molars, first and second premolars, and central and lateral incisors. The contralateral canine was used as the unanesthetized control to ensure that the pulp tester was operating properly and that the subject was responding appropriately during each experimental portion of the study. Clinical examinations were done prior to subject inclusion to ensure that all teeth were free of caries, large restorations, and periodontal disease; no patients had a history of trauma or sensitivity.

Before the experiment, the two sets of IAN blocks were randomly assigned six-

digit numbers from a random number table. Each subject was randomly assigned to one

of the two sets of IAN blocks to determine which set would be administered at each

appointment. The anesthetic solutions administered were blinded by removing the labels

from each of the cartridges, and the cartridges were then labeled with the six-digit numbers. The colors of the cartridge tips and rubber stoppers were identical for both types of anesthetics. The expiration dates on the cartridges were checked before the labels were removed. Only the random numbers were recorded on the data collection sheets to blind the experiment. Only the principal investigator and co-investigator had access to the master list.

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At the beginning of each appointment and before any injections were given, the experimental teeth and control contralateral canine were tested three times with the electric pulp tester (Kerr, Analytic Technology Corp., Redmond, WA) to record baseline vitality. After the tooth to be tested was isolated with cotton rolls and dried with gauze, toothpaste (Crest Cavity Protection®, Procter & Gamble, Cincinnati, OH) was applied to the probe tip, which was placed half way between the gingival margin and the occlusal or incisal edge of the tooth. The patient held a grounding wire to complete the circuit. The current rate was set at 25 seconds to increase from no output (0) to the maximum output

(80). The number associated with the initial sensation was recorded. If the patient had no sensation, testing was stopped and a value of 80 was recorded. Trained research personnel performed all pre-injection and post-injection tests. The trained research assistants were dental or hygiene students specifically trained in conducting this clinical trial.

Before the IAN block injection, each subject was informed of the pain rating for injection pain and shown the visual analog scale (VAS). A Heft-Parker VAS (103)

(APPENDIX F) was used in this study. The VAS was a 170-mm line with various

descriptive terms. Immediately after each IAN block, each subject rated the pain for

needle insertion, needle placement and solution deposition on the VAS by placing a mark

on the scale where it best described their pain level. To interpret the data, the VAS was

divided into the following four categories. No pain corresponds to 0 mm on the scale.

Mild pain was defined as greater than 0 mm and less than or equal to 54 mm. Mild pain

included the descriptors of “faint”, “weak”, and “mild” pain. Moderate pain was defined

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as greater than 54 mm and less than 114 mm and included the descriptor of “moderate”

pain. Severe pain was defined as equal to or greater than 114 mm. Severe pain included

the descriptors of “strong”, “intense”, and “maximum possible” pain.

Topical anesthetic gel (0.2 mL) (20% benzocaine, Benco Dental, Pittston, PA)

was passively placed at the dried IAN block injection site for 60 seconds using a cotton

tip applicator. A standard IAN block (46) was administered with a 27-gauge 1½-inch needle (Monoject; Sherwood Medical, St. Louis, MO) attached to a standard aspirating syringe. With the subject’s mouth wide open, the thumb of the non-injecting hand was

placed over the pterygomandibular triangle and then pulled laterally until a depression in

the anterior border of the ramus was felt. The posterior portion of the ramus was palpated

with the first or second finger of the non-injecting hand until a slight depression was

located. The vertical height of the injection site was determined by the line between the

thumb and the finger. The direction of the needle insertion was from the contralateral

mandibular premolars and aligned parallel to the occlusal plane. The needle was

advanced until bone was sounded, then retracted 1 mm. After the block target area was

reached and aspiration performed, 1.8 mL of anesthetic solution (either 3% mepivacaine

or 2% lidocaine with 1:100,000 epinephrine) was deposited over a 1½ minute (90 sec.)

time period. The mouth was then rinsed with water and aspirated, and the subject rated

the pain from the first injection on the first VAS. One minute following the first injection,

a second cartridge (1.8 mL) of anesthetic solution (2% lidocaine with 1:100,000

epinephrine) was administered as described above. The subject then rated the pain of the

second injection on a second VAS. All injections were given by one operator (EL).

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During the first 15 minutes of testing, each subject was asked if his or her

lip/tongue were numb every minute. If profound lip numbness was not recorded within

15 minutes, the block was considered unsuccessful; the subject was then reappointed.

At 1 minute after the second IAN block, the first and second molars were tested

with the electric pulp tester. At 2 minutes, the first and second premolars were tested. At

three minutes, the lateral and central incisors were tested. At 4 minutes, the control

canine was tested. This cycle of testing was repeated every 4 minutes. At every third

cycle the control tooth, the contralateral canine, was tested by a pulp tester tip that was

not connected to the unit to test the reliability of the subject. Unreliable subjects were

disqualified from the study. All testing was stopped at 56 minutes post-injection.

No response from the subject at the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when the first of two consecutive 80 readings was obtained by the fifth testing period (17 minutes) and the 80 reading was continuously sustained for 56 minutes.

Anesthesia was considered a failure if the subject never achieved two consecutive 80 readings during the 56 minutes, or if the anesthesia was defined as slow onset, non- continuous, or short duration. Onset of pulpal anesthesia was recorded at the time of the first of two consecutive 80 readings. Anesthesia of slow onset was defined as the subject achieving two consecutive 80 readings later than 17 minutes following the second IAN block injection. Non-continuous anesthesia was defined as onset of anesthesia which was not continuously sustained for 56 minutes. Anesthesia of short duration was defined as onset of anesthesia which was not sustained for the full 56 minutes.

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Comparisons between the sets of anesthetic solutions for anesthetic success,

failure, slow onset and incidence of pulpal anesthesia (percentage of 80 readings across

time) were analyzed nonparametrically using Exact McNemar tests with p-values

adjusted using the Step-down Bonferroni method of Holm. Between-anesthetic solution differences in pain ratings for needle insertion, needle placement and solution deposition were analyzed using multiple Wilcoxon matched-pairs, signed ranks tests with p-values adjusted using the Step-down Bonferroni method of Holm. Between-gender pain comparisons were assessed using multiple Mann-Whitney-Wilcoxon tests and the Step- down Bonferroni method of Holm. Comparisons were considered significant at p<0.05.

With a non-directional alpha risk of 0.05 and assuming a total proportion of discordant pairs of 0.5, a sample size of 100 subjects was required to demonstrate a difference of ±20 percentage points in anesthetic success with a power of 0.82. With a non-directional alpha risk of 0.05 and assuming a standard deviation of 27.4, a sample size of 100 subjects provided a power of 0.82 to demonstrate a difference ± 10 points on the visual analogue scale.

The pH of each anesthetic solution was tested. Three random samples of 3% mepivacaine and 2% lidocaine with 1:100,000 epinephrine were subjected to three readings each with the Orion Star AIII pH meter (Thermo Scientific, Beverly, MA). The pH tester was calibrated with pH buffers (NIST Traceable Solution, OAKTON®, Vernon

Hills, IL) prior to testing.

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RESULTS

One hundred subjects (50 males, 50 females) were included in this study. Subjects

ranged in age from 18 to 38 with a mean age of 25.6 years (Table A-1). All subjects were classified as ASA I or II as indicated on a health history (Appendix C) filled out by the

subject and oral questioning.

Subjects rated each phase of anesthetic injection (insertion, deposition,

placement) on a 170-mm Heft-Parker VAS form (Appendix F). Table A-2 shows the mean pain ratings for each phase of the first injection and for each anesthetic combination.

For the first injection, the mean VAS pain ratings for needle insertion were as follows: mepivacaine 42.7 mm, lidocaine 43.5 mm. There was no significant difference between the two anesthetics regarding needle insertion pain (p>0.05). While females reported more pain than males, no significant differences in insertion pain were seen between subject genders. The means for both anesthetics were in the “mild” category on the VAS.

The mean VAS pain ratings for needle placement during the first injection were as follows: mepivacaine 55.6 mm, lidocaine 57.1 mm. There was no significant difference between the two anesthetics regarding needle placement pain (p>0.05). The means for both anesthetics were in the “moderate” category on the VAS. Subject gender

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did not have a significant effect on needle placement pain reported, although females

reported more pain than males.

Regarding the first injection, the mean VAS pain ratings for solution deposition

were as follows: mepivacaine 41.2 mm, lidocaine 39.1 mm. There was no significant

difference between the two anesthetics regarding solution deposition (p>0.05). The

means for both anesthetics were in the “mild” category on the VAS. Females rated

solution deposition of mepivacaine significantly (p=0.0001) more painful than males.

The summary of injection pain ratings from the first injection can be found in

Table A-4. Utilizing lidocaine, subjects reported none-to-mild pain in 80% of needle insertions, 62% of needle placements, and 84% of solution depositions. With mepivacaine, subjects reported none-to-mild pain in 83% of needle insertions, 62% of needle placements, and 78% of solution depositions.

Table A-3 shows the mean pain ratings during each phase of the second injection.

The summary of these ratings can be found in Table A-5. As the patient was partially anesthetized from the first injection, one would expect the reported pain from the second injection to be lower; therefore, no analysis of this data was completed.

In both anesthetic groups needle placement during the first injection had the highest mean pain ratings of the three phases of injection, but there were no significant differences between the solutions used. Females rated solution deposition of mepivacaine significantly more painful than lidocaine (Table A-2), but both anesthetics were rated in the “mild” category. Females reported more pain during all phases of injection (Table A-

2) versus males, although these differences were smaller for the second injection.

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Anesthetic success was defined as achieving the first of two consecutive 80/80

(maximum) readings with the electric pulp tester by the fifth testing period (17 minutes

post-injection) and sustaining that reading for the remainder of the 56 minute testing

period. All subjects that were included had profound lip numbness at this time. Six

subjects were reappointed because they did not have lip numbness at 15 minutes post-

injection (4 lidocaine/lidocaine, 2 mepivacaine/lidocaine). One subject was disqualified

due to unreliable pulp testing responses. Success rates for mepivacaine/lidocaine and

lidocaine/lidocaine, respectively are as follows: second molar (51.5%, 56.6%), first molar

(44.0%, 40.0%), second premolar (44.7%, 40.4%), first premolar (52.6%, 49.5%), lateral incisor (30.0%, 27.0%), and central incisor (10.1%, 10.0%). The highest success was seen in second molars, and the lowest success was in the central incisor. The mepivacaine/lidocaine combination group generally had a higher success rate, with the exception of the second molar; however, there were no significant differences between the two anesthetic groups for any of the teeth tested. It should be noted that some subjects had teeth previously extracted for orthodontic considerations (mandibular first and second premolars, mandibular second molars) resulting in N<100 (Table A-6).

Anesthetic failure was defined as the absence of two consecutive 80/80

(maximum) readings with the pulp tester throughout the entire testing period. Failure was seen in the mepivacaine/lidocaine and lidocaine/lidocaine groups as follows: second molar (13.1%, 12.1%), first molar (30.0%, 28.0%), second premolar (22.6%, 26.9%), first premolar (13.4%, 21.6%), lateral incisor (52.0%, 54.0%), and central incisor (72.0%,

75.0%). The lidocaine/lidocaine group generally had a higher failure rate in premolars

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and incisors, while the mepivacaine/lidocaine group had a higher failure rate in the

molars. The failure rate generally increased from posterior to anterior, with the exception

of the first molar having a higher failure rate than the premolars. The central incisor had

the highest failure rate. No significant difference was seen for failure between the two

anesthetic groups for the teeth tested (Table A-7).

It should be noted that the percentages of success and failure do not add up to

100%. This is due to a group of teeth that fell into neither category. These teeth can be classified into the following categories: anesthesia of slow onset (two consecutive 80/80 readings obtained after the fourth testing period), anesthesia of short duration (80/80 readings were obtained but lost before the end of the testing period), and/or non- continuous anesthesia (80/80 readings were obtained, lost, and re-obtained). Clinically, anesthesia of these teeth would not be considered successful.

Comparisons of pulpal anesthesia over time can be seen in Tables A-9 through A-

14 and Figures 1-6. No significant differences were seen between the two anesthetics for any tooth.

Tables A-14 and A-15 show times for onset and duration of anesthesia. Generally, posterior teeth were numb before anterior teeth. The mean onset times for the mepivacaine/lidocaine group ranged from 6.9 to 16.2 minutes, while mean onset times ranged from 6.0 to 12.2 minutes for the lidocaine/lidocaine group. Duration of anesthesia ranged from 4 to 52 minutes in both groups. No differences in onset or duration were seen between the two anesthetics.

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The mean pH of mepivacaine was registered as 6.69, and the mean pH of lidocaine was 4.28. The difference in pH was significant (p<0.0001) (Table A-16).

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DISCUSSION

One hundred asymptomatic adult subjects (50 males, 50 females) volunteered to participate in this study. Subjects ranged in age from 18 to 38 years with a mean age of

25.6 years (Table A-1). Inclusion criteria required subjects to be between the ages of 18 and 65 years. No minors (<18 years) were allowed to participate as they are unable to provide consent. Nordenram and Danielsson (104) found that local infiltration injections were more effective in elderly patients versus a younger age group. The authors speculated that this may be due to a higher pain threshold in the elderly. For this reason, subjects greater than 65 years of age were excluded from this study.

Subjects were required to be in good health as determined by a written health history and oral questioning. Exclusion criteria were as follows: history of significant medical issues (ASA Classification of III or greater), allergy to local anesthetics or sulfites, or taking any medications (analgesics, alcohol, anti-depressant or anti-anxiety medications) that would alter perception of pain or metabolism of anesthetics. Opioid analgesics act at central and peripheral sites and influence the response to a painful stimulus (105), and while the main action of non-steroidal anti-inflammatory drugs

(NSAIDs) is in response to peripheral inflammation, NSAIDs have also demonstrated central effects (106, 107). Consumption of ethanol has an inhibitory effect on the CNS,

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which causes anxiolysis and anesthesia (105). Tricyclic antidepressants (TCAs) inhibit

the neuronal uptake of catecholamines which results in an increased catecholamine

concentration at the sympathetic neuroeffector junction (43, 108). Boakes et al. (109)

noted a 2-4 fold potentiation of cardiovascular effects with subsequent administration of and adrenaline, and suggested that the interaction of TCAs and local anesthetics used in dentistry could be hazardous. TCAs also have analgesic action, as they are often effective in the treatment of neuropathic pain (105). Anti-anxiety medications also have CNS depressant effects, which may affect interpretation of pain

(105). These exclusion criteria were intended to eliminate any potential confounding factors that may affect the results of this study.

Female subjects were questioned regarding pregnancy and were not allowed to participate if pregnant, suspected a pregnancy, trying to become pregnant, or lactating. If a pregnancy was suspected, female subjects were required to take a urine pregnancy test before each appointment. Local anesthetics and vasoconstrictors used in dentistry are considered to be safe to administer in the pregnant patient (20, 110); however, pregnant patients were eliminated from this study due to medico-legal reasons. Congenital anomalies occur naturally in 3% of the general population, yet the cause cannot be determined in over 50% of these cases (111). The risks of associating such an event with this study were deemed to be too high; therefore, pregnant subjects were not allowed to participate.

Females have been shown to report higher levels of pain, more frequent pain, and pain of longer duration versus males (112). Liddell and Locker found that women report

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higher levels of dental anxiety, and that they are less accepting of pain versus males

(113). Keogh et al. showed that females are less tolerant to cold pressor pain than males

(114). Fillingim et al. (115) suggested that due to these gender differences, experimental

pain responses may be more clinically relevant for females than males. Unbalanced

gender groups in the current study could have resulted in higher or lower reported

injection pain scores that may mistakenly be attributed to the effect of the anesthetic

solution. For these reasons, males and females were balanced and also separately

evaluated regarding injection pain.

Prior to injection, each subject was informed how to rate injection pain and shown

the visual analog scale (VAS) which was used to record any pain. The VAS is considered

to be the most sensitive method for measuring pain as compared to simple descriptive,

nominal, and nonverbal methods (116). A Heft-Parker VAS was used in this study. Heft and Parker (103) showed that pain categories should not be equally spaced on a VAS, and that it is important for the verbal descriptors used (faint, weak, mild, moderate, strong, intense, severe) to correspond with their location on the scale. The Heft-Parker VAS

combines a graphic rating scale with a visual analog scale, yet allows subjects the ability

to mark any point along the line. It has been noted, however, that subject responses tend

to be grouped around the verbal descriptors (103). Although a four-point scale was used in many of the previously reviewed studies, Kreimer et al. (77) showed that the category of rated pain corresponded well when comparing a four-point scale to the Heft-Parker

VAS. Subjects in the current study were instructed to rate the pain experienced during injection phases of needle insertion, needle placement, and solution deposition.

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Injection Pain

Needle Insertion

Needle insertion pain was measured in this study. Regarding the first injection,

80% of subjects (88% of males, 72% of females) reported none-to-mild pain during

needle insertion in the lidocaine/lidocaine group, while 83% of subjects (86% of males,

80% of females) reported none-to-mild pain during needle insertion in the mepivacaine/lidocaine group (Table A-4). When comparing to the range of pain scores from previous studies (Table 5-1), our results fall somewhere near the middle. No differences between the two groups were seen, which is expected as the type of anesthetic used would not have an impact at this stage of injection. Although not statistically significant, females reported higher levels of pain during needle insertion regardless of anesthetic group (Table A-2).

Factors influencing the pain of needle insertion may include needle gauge, use of topical anesthetic, subject gender, and operator differences (20, 47, 112, 117-121).

Flanagan and coauthors evaluated 25- and 27-gauge needles for inferior alveolar nerve block (IANB) injections (117). They determined that there was no difference in reported injection pain between the different needle gauges. Brownbill et al. (118) found no difference of injection pain between 25- and 30-gauge needles in children during the

IANB. A study by Fuller, Menke, and Meyers showed no differences in the perception of pain produced by penetrations of 25-, 27-, and 30-gauge needles in the retromolar fossa

(119). These studies indicate that it is unlikely that needle gauge has a large impact on needle insertion pain. The most commonly used needle in dentistry is the 27-gauge long

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needle (20). As many other anesthetic studies evaluating injection pain during the IANB

have used a 27-gauge needle, it was determined that it should also be used in the current

study so that our results are directly comparable.

The usefulness of topical anesthetic for the IANB has been widely debated. Gill

and Orr (122) found that topical anesthetic had no effect on palatal injection pain;

however, Rosa et al. (123) found a significant decrease in pain with 20% benzocaine and

5% lidocaine versus placebo in the palate. Rosivack et al. (124) concluded that 20%

benzocaine and 5% lidocaine significantly reduced pain during needle insertion versus

placebo in the mucobuccal fold above the maxillary canine. Mikesell (125) found that

injection pain was significantly reduced when using topical anesthetic versus placebo in

maxillary infiltrations. However, none of these studies evaluated the use of topical with

the IANB injection, and injection discomfort can be affected by the area of the mouth that

is injected (126).

The effectiveness of 20% benzocaine as a topical anesthetic was evaluated in a

retrospective study by Nusstein and Beck (47). Moderate-to-severe pain to needle insertion was reported by 14-22% of subjects during the IANB, whether or not they received topical anesthetic prior to needle insertion, and there was no significant difference reported between the two groups. Nakanishi et al. (120) found that while topical 20% benzocaine reduced injection pain in the anterior mandibular mucobuccal fold, it was not effective for the IANB injection. Nist (127) found no difference in needle insertion pain between the topical application of 20% benzocaine, Vaseline, or no treatment prior to an IANB injection. The results of these studies make it reasonable for

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one to conclude that topical anesthetic may be of no benefit to patients receiving the

IANB; however, Martin and coauthors (121) suggested that psychologic factors may play

a more important role when topical anesthesia is used to reduce the pain of dental

injections, and Meit et al. (128) found that 93.4% of dentists use topical anesthetic.

Acknowledging that there is some potential benefit to using topical anesthetic, it was

utilized in the current study.

The percentage of asymptomatic subjects in previously reviewed studies reporting

none-to-mild pain during the needle insertion phase of an IANB injection can be

referenced in the following table:

Author None-to-mild pain Moderate-to-severe pain Childers (50) 84% 16% Dunbar (51) 96% 5% Reitz (52) 90% 10% Clark (53) 82% 18% Willett (54) 87% 13% Whitcomb et al. (55) 95% 5% Wolf (57) 86% 14% Guglielmo (58) 74% 26% Mikesell (59)* 71% 29% Goodman (60)* 88% 12% Steinkruger (61)* 92% 8% Elmore (62)* 64% 36%

*topical anesthetic was used.

Table 5-1. Needle insertion pain reported by category.

All of the preceding studies used a 27-gauge needle, similar to this study. Mean pain

scores for needle insertion pain during both injections in the current study were in the

mild category (Tables A-2 and A-3). While our study does not show any improvement over the referenced studies, it is certainly consistent with previous results.

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Needle Placement

Pain experienced during needle placement may be influenced by the injection

technique, gender, or operator differences (20, 55, 57, 59, 60, 68, 112). Some clinicians

have deposited a small amount of anesthetic solution during needle placement in the hope

that an immediate anesthetic effect would result in less pain for the patient (55, 57, 59,

60, 68); however, it does not appear that this technique has reduced the pain reported.

Nusstein and coauthors evaluated the effects of a 2-stage injection technique on IANB

injection pain (68). Females reported significantly less pain during needle placement with

the two-stage injection versus a conventional injection.

In the current study, needle placement was the most painful stage of injection for

both anesthetic groups and for both genders. Regarding the first injection, 62% of

subjects (74% of males, 50% of females) reported none-to-mild pain during needle

placement in the lidocaine/lidocaine group, while 62% of subjects (68% of males, 56% of

females) reported none-to-mild pain during needle placement in the mepivacaine/lidocaine group (Table A-4). These results are within the range found in

previous studies, although the number of subjects reporting none-to-mild pain is on the lower end. This may be due to operator differences. No differences between the two anesthetic groups were seen, which is expected as the type of anesthetic used would not have an impact at this stage of injection. Although not statistically significant, females reported higher levels of pain versus males during needle placement regardless of anesthetic group (Table A-2). The mean pain scores on the VAS for females during needle placement were 63.8 mm (lidocaine/lidocaine group) and 62.4 mm

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(mepivacaine/lidocaine group). While these scores were not statistically higher than in

males (50.5 mm for lidocaine/lidocaine, 48.7 mm for mepivacaine/lidocaine- both in the mild range), they were within the moderate pain range, which may have some clinical significance.

Although needle placement pain is reported as none-to-mild by a majority of patients receiving the IANB injection, it appears to be slightly more painful than needle insertion as a higher percentage of subjects have reported moderate-to-severe pain during this phase. Results from previous studies utilizing the conventional IANB technique in asymptomatic subjects can be seen below:

Author None-to-mild Moderate-to-severe Childers (50) 65% 35% Dunbar (51) 77% 24% Reitz (52) 85% 15% Clark (53) 62% 38% Willett (54) 56% 45% Guglielmo (58) 78% 22% Elmore (62) 51% 49% Mikesell (59)* 40% 60% Goodman (60)* 71% 29% Whitcomb et al. (55)* 78% 22% Wolf (57)* 83% 18% Nusstein et al. (68)* 65% 35% Nusstein et al. (68)† 79% 22%

* anesthetic was deposited as the needle was advanced to the target site. † 2-stage injection technique.

Table 5-2. Needle placement pain reported by category.

Gender was not evaluated separately in any of the preceding studies, except for Elmore

(62) who found no difference during needle placement. With mean pain scores for

females in the moderate range during needle placement in the current study, the gender

effect certainly warrants further research. It is also obvious when looking at these studies

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that operator differences can greatly influence pain reported. While our results fall within

the range of previous studies, we showed fewer subjects reporting none-to-mild pain during needle placement than a majority of authors. More research evaluating operator differences could also be helpful in reducing the pain of needle placement.

Solution Deposition

Subjects recorded the pain of solution deposition in this study. Factors influencing the pain of solution deposition may include: speed of injection, volume of anesthetic injected, type of anesthetic, presence/absence of a vasoconstrictor or other additives, and subject gender (48, 49, 54, 55, 57-60, 63, 65, 70-72, 74, 75, 112, 129-131). Kanaa and coauthors (70) showed that a slow (60 seconds) IANB injection of 2.0 mL 2% lidocaine with 1:80,000 epinephrine was significantly less painful than a fast injection (15 seconds). This is likely due to the higher tissue pressure that is caused from the fast injection of anesthetic. Kudo (129) measured injection pressure during fast and slow injections and assessed the pain and anxiety of male subjects. A significant correlation was noted between injection pressure and pain, and between injection pressure and anxiety. While this same phenomenon might be expected with the injection of a larger volume of anesthetic solution, Vreeland et al. (63) found no significant difference in solution deposition pain when comparing 1.8 mL and 3.6 mL solutions deposited over two minutes with the IANB injection.

The type of anesthetic used has been suggested to have an effect on pain during solution deposition (20, 48, 49, 74). In general, solutions containing a vasoconstrictor

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have a lower pH than plain solutions because they are acidified with an antioxidant by the

manufacturer to prolong the shelf life. Sodium bisulfite is commonly added to slow the

oxidation of epinephrine in commercially prepared solutions; it reacts with oxygen to

form sodium bisulfate which has an even lower pH. It has been suggested that injection

of plain anesthetic solutions should be more comfortable due to their higher pH (20). This may be because it takes the body less time to buffer tissue fluids to normal levels. A review of the medical literature shows that buffering local anesthetics with sodium bicarbonate closer to physiologic pH (7.4) significantly reduces the pain of injection (71),

but this same effect has been debated in the dental field. Whitcomb et al. (55) showed no

difference in solution deposition pain between lidocaine buffered with sodium

bicarbonate and non-buffered lidocaine solutions for the IANB injection. Ridenour et al.

(73) reported 80% of subjects experienced none-to-mild pain during IANB injection of a sodium bicarbonate-buffered solution, which is similar to the results of our study with

non-buffered anesthetics (Table 4). In a study by Kashyap et al. (72), it was reported that

84% of subjects experienced none-to-mild pain with a non-buffered anesthetic solution

and 100% of subjects experienced no pain during injection of a sodium bicarbonate-

buffered anesthetic solution. In that study; however, pain was not recorded by the subject

but was assessed by the operator based on the subject’s response to questioning and

behavioral signs. While the operators were blinded to the anesthetic used, it is possible

that there was some operator bias in this study or a failure to properly recognize all

patient signs.

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In the current study, each first injection consisted of 1.8 mL of either 2% lidocaine with 1:100,000 epinephrine or 3% mepivacaine deposited over 90 seconds.

None-to-mild pain when utilizing mepivacaine and lidocaine was reported during 78% and 84% of injections, respectively (Table A-4). Mean pain scores with mepivacaine

(41.2 mm) and lidocaine (39.1 mm) were both in the mild pain range (Table A-2). While no significant differences between the two solutions were seen overall, analyzing genders separately showed that females found solution deposition of mepivacaine significantly more painful than lidocaine (mean VAS = 53.2 mm vs. 43.9 mm, p=0.0001) (Table A-2).

Females also reported significantly more pain to solution deposition than males (Table A-

2). The pH of the solutions used in the current study were recorded as lidocaine = 4.28 and mepivacaine = 6.69 (Table 16). Under the assumption that a significant difference in solution pH should result in a significant difference in pain during solution deposition, one would expect that the injection of mepivacaine would be less painful than lidocaine.

However, our results indicate no difference between the two solutions with a tendency of less pain with the lidocaine solution. This is the opposite of what we expected to find.

A study by Kramp and coauthors (48) concluded that the use of 4% prilocaine plain for IANB injections resulted in significantly less pain than the other solutions tested, with no difference between 2% lidocaine with 1:100,000 epinephrine and 2% mepivacaine with 1:20,000 levonordefrin. They hypothesized that this difference is due to the pH difference of the anesthetic solutions, which were recorded as follows: lidocaine = 4.12; mepivacaine = 3.05; prilocaine = 6.28. It should be noted that the lidocaine and mepivacaine each had a lower pH due to the presence of the

79 vasoconstrictor. All mean pain scores were in the mild range, so these results may not be clinically significant.

Wahl, Schmitt, and Overton (74) evaluated injection pain of 4% prilocaine plain,

3% mepivacaine plain, 4% articaine with 1:100,000 epinephrine, and 2% lidocaine with

1:100,000 epinephrine in patients undergoing routine dental procedures. For the IANB,

609 subjects reported the following mean pain scores on a ten-point scale: articaine =

3.33 (56.6 mm on a 170-mm VAS), lidocaine = 3.14 (53.4 mm on a 170-mm VAS), mepivacaine = 3.12 (53.0 mm on a 170-mm VAS) and prilocaine = 2.66 (45.2 mm on a

170-mm VAS). The authors concluded that prilocaine was significantly less painful

(p<0.001), and hypothesized that this may be associated with the higher pH of the solution. The pHs of the anesthetic solutions, as measured by the authors, were recorded as follows: prilocaine = 5.5-6.5; lidocaine = 4.0-4.5; articaine = 3.5-4.5; mepivacaine =

4.5-5.5. While there was a statistically significant finding, it is difficult to say whether this was clinically significant or not. With a VAS difference of less than 10 mm

(converted to the 170-mm VAS) and three of the four solutions reported in the mild pain range, patients may not experience noticeably less pain with the injection of a higher pH solution.

Wahl and coauthors (49) evaluated pain of injection between 4% prilocaine plain and 2% lidocaine with 1:100,000 epinephrine in patients receiving the IANB prior to undergoing routine dental procedures. No significant difference was found between the two solutions. The mean pain scores were in the none-to-mild range. Sumer et al. (sumer) found no differences in the injection pain of 4% articaine with 1:200,000 epinephrine, 3%

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prilocaine with 1.08 µg phenylpressin, and 2% lidocaine with 1:100,000 epinephrine.

Subjects reported none-to-mild pain for 75.4% of injections.

Morris et al. (130) evaluated the pain of intradermal and subcutaneous injection of

different local anesthetic solutions and found that 1% mepivacaine was significantly

more painful than 1% lidocaine. The authors stated that the mechanism of pain produced

by local anesthetics is unknown; however, it appears to be unrelated to the formulation of

the anesthetic solutions. That is, the components of the anesthetic solution may not be as

important to injection pain as the chemical structure of the anesthetic molecule. McKay et

al. (131) found that while increasing the pH of a particular anesthetic with sodium

bicarbonate may decrease the pain of injection, the cause of pain is complex and likely

depends on factors other than pH alone. The effect of pH does not appear to be relevant

when comparing different agents (130).

Mikesell (59) found no difference in solution deposition pain between 2%

lidocaine with 1:100,000 epinephrine and 4% articaine with 1:100,000 epinephrine for

IANB injections. McLean (65) reported no significant difference in solution deposition pain during the IANB between 2% lidocaine with 1:100,000 epinephrine and 3% mepivacaine, with 70-73% of subjects reporting none-to-mild pain. Ninety-three percent of subjects in a study by Guglielmo (58) reported none-to-mild pain during solution deposition of 3% mepivacaine for the IANB. Even with these clinical findings, many practitioners use a combination of mepivacaine and lidocaine because they believe it results in less pain for their patients. In theory, the higher pH of mepivacaine should result in a less painful injection than lidocaine, and one would expect this difference to be

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evident during the stage of solution deposition. Results of previous studies on

asymptomatic subjects involving these two anesthetics for IANB can be found below:

Author Anesthetic Volume Speed None/mild Moderate/severe Vreeland et al. (63) 2% Lidocaine 1.8 mL 2 minutes 67% 33% Hinkley (64) 2% Lidocaine 1.8 mL 1 mL/min 90% 10% Nist (69) 2% Lidocaine 3.6 mL 2 minutes 75% 25% McLean (65) 3% Mepivacaine 1.8 mL 1 mL/min 73% 27% McLean (65) 2% Lidocaine 1.8 mL 1 mL/min 70% 30% Childers (50) 2% Lidocaine 1.8 mL 2 minutes 83% 18% Dunbar (51) 2% Lidocaine 1.8 mL 2 minutes 79% 21% Reitz (52) 2% Lidocaine 1.8 mL 1 minute 99% 1% Clark (53) 2% Lidocaine 3.6 mL 2 minutes 58% 42% Yonchak (66) 2% Lidocaine 3.6 mL 2 minutes 93% 8% Mikesell (59) 2% Lidocaine 1.8 mL 1 minute 81% 20% Goodman (60) 2% Lidocaine 1.8 mL 2 minutes 83% 18% Steinkruger (61) 2% Lidocaine 1.8 mL 1 minute 84-86% 14-16% Goldberg et al. (67) 2% Lidocaine 3.6 mL 2 minutes 86% 15% Willett (54) 2% Lidocaine 1.8 mL 1 minute 64% 36% Whitcomb et al. (55) 2% Lidocaine 3.6 mL 2 minutes 93% 8% Wolf (57) 2% Lidocaine 1.8 mL 1 minute 67% 33% Elmore (62) 2% Lidocaine 1.8 mL 1 minute 48% 52% Guglielmo (58) 3% Mepivacaine 1.8 mL 1 minute 93% 8%

Table 5-3. Solution deposition pain reported by category.

Pain reported during solution deposition in our study is consistent with results of previous

studies utilizing these anesthetics. It should be noted, however, that direct comparison

can only be made to the studies utilizing 1.8 mL of 2% lidocaine with 1:100,000

epinephrine (50-52, 54, 57, 59-65) or 3% mepivacaine (58, 65).

Other additives to the anesthetic solution may also influence the pain of solution

deposition. In a study by Willett (54), 50% of subjects reported severe pain when injected

with diphenhydramine for the IANB, but no difference was seen between lidocaine and a

combination of lidocaine and diphenhydramine. Wolf (57) showed no difference in

solution deposition pain during the IANB with the addition of mannitol to lidocaine. The

addition of meperidine to lidocaine in a study by Goodman (60), resulted in subjects

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reporting significantly more pain during the IANB (as compared to a regular solution of lidocaine) even though the pHs of the solutions were similar, with the mean VAS score in the moderate pain category (55.4 mm). Again, this suggests that pain during solution deposition when comparing different anesthetics is not likely due to pH.

No difference in pain has been reported regarding gender with the conventional

IANB injection, although a two-stage technique resulted in significantly less pain during needle placement in females (68). Of the studies reviewed, only Elmore (62) evaluated the effects of subject gender on injection pain during the IANB, but no differences were found. Further evaluation or research may be warranted to look into the gender effect.

Females have been shown to report higher levels of pain, more frequent pain, and pain of longer duration versus males (112). Liddell and Locker found that women report higher levels of dental anxiety, and that they are less accepting of pain versus males (113).

Keogh et al. showed that females are less tolerant to cold pressor pain than males (114).

Fillingim et al. (115) suggested that due to these gender differences, experimental pain responses may be more clinically relevant for females than males. In the current study, gender groups were balanced and analyzed separately regarding injection pain to eliminate gender as a confounder when evaluating the effect of the anesthetic solution on injection pain.

In our study, females reported higher levels of pain in all phases of injection as compared to males (Table 2). During the phases of needle insertion, needle placement, and solution deposition, males reported mean pain ratings of 37.6-39.3 mm, 48.7-50.5

mm, and 29.1-34.3 mm, respectively. Females reported mean pain ratings of 46.0-49.3

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mm, 62.4-63.8 mm, and 43.9-53.2 mm, respectively. The only difference that was

significant between genders was during solution deposition of mepivacaine (p=0.0001).

One other potential confounding factor appears to be the operator- the person giving the injection. If all variables in the above-listed studies are controlled (ex- needle size, injection type, injection technique, anesthetic type, etc.) operator appears to have a large impact; that is, some operators appear to have caused more moderate-to-severe pain during injection than others, or the patient population sampled reported more pain (53,

54, 59, 62). Further research needs to be conducted to look at this aspect. Operator technique differences influence the pain experienced by subjects during all phases of injection. This was not a confounder of the current study, however, as all injections were given by a single operator (EL).

Each second injection in our study consisted of 1.8 mL of 2% lidocaine with

1:100,000 epinephrine deposited over 90 seconds. Mean pain ratings were recorded for this injection (Table A-3) and are summarized in Table A-5. As the patient was partially anesthetized from the first injection, one would expect the reported pain from the second injection to be lower; therefore, no analysis of this data was completed. However, pain ratings were noted to be much lower during the second injection versus the first, and the difference between genders was smaller although females still tended to report more pain than males.

While we were hopeful that the combination of mepivacaine and lidocaine would result in a less painful injection experience for patients, we were unable to show a difference in solution deposition pain between the two anesthetics. As suggested by

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Morris et al. (130), it appears that pH is not a significant factor in injection pain when

comparing two different solutions. More research is needed in this area to determine what

components of an anesthetic solution are related to solution deposition pain.

Pulpal Anesthesia

Anesthetic Success

The ability of the anesthetic combinations to provide successful pulpal anesthesia

was also evaluated. The experimental teeth selected for this study were the mandibular

first and second molars, first and second premolars, and central and lateral incisors. The

contralateral canine was used as the unanesthetized control to ensure that the electric pulp

tester (EPT) was operating properly and that the subject was responding appropriately

during each experimental portion of the study. This study used a Kerr (Analytic

Technology Corp., Redmond, WA) EPT. Vital, asymptomatic pulps were evaluated in

virgin or minimally restored teeth. All experimental teeth were determined to be vital by

a positive response to testing with the EPT two times at the beginning of each

appointment. Lundy and Stanley (132) determined that there was no correlation between

the pulpal status and the EPT value, but that a negative (80/80) reading indicated a

necrotic pulp. All pulp testing was done by the principal investigator or a trained research

assistant, both of whom were blinded to the anesthetic combination used. Two

consecutive 80/80 readings on any tooth, teeth exhibiting active caries, periodontal

disease, extensive restorations, history of trauma or symptoms, or teeth missing for

reasons other than orthodontic considerations resulted in the disqualification of that

85 particular quadrant of the subject’s mouth. Eleven subjects had teeth previously extracted for orthodontic reasons resulting in N<100 (Table A-6). One subject was dismissed from the study due to unreliable responses during pulp testing.

An electric pulp tester (EPT) was used to measure pulpal anesthesia in this study.

Certosimo and Archer (133) evaluated the level of local anesthesia experienced by patients undergoing operative dental procedures. Readings were taken with an EPT before and after injection of anesthetic. Teeth were then prepared for restoration, and subjects rated their level of anesthesia on a VAS form. EPT readings of less than 80/80 resulted in pain during the procedure. Their results indicated that the EPT is a valuable tool in predicting pulpal anesthesia in asymptomatic carious teeth. Dreven and coauthors

(134) evaluated the pulpal anesthesia of teeth in symptomatic and asymptomatic subjects presenting for endodontic treatment. They showed that with an 80/80 reading, profound anesthesia during endodontic treatment occurred in 100% of asymptomatic patients and

73% of subjects with symptomatic irreversible pulpitis. Modaresi et al. (135) confirmed that EPT can be an accurate device in determining pulpal anesthesia in asymptomatic teeth.

The traditional definition of anesthetic success for an IANB injection is numb within 15 minutes of injection and sustaining anesthesia for 60 minutes. This definition is used because it is clinically practical: dentists want patients to obtain anesthesia within a reasonable amount of time and maintain anesthesia during the entire dental procedure.

This definition of success was used in the current study and is used in most studies referenced in this discussion unless otherwise noted.

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The current study is the first to evaluate the combination of 3% mepivacaine plain

and 2% lidocaine with 1:100,000 epinephrine in human subjects. Some clinicians use

these anesthetics together for IAN blocks. The thought behind this is that 3%

mepivacaine has more anesthetic molecules available to block sodium channels due to its

higher concentration and that it also has a higher pH (pH = 6.69) because it does not

contain epinephrine. Both of these conditions may provide more of the base form of the

anesthetic for the IANB initially, therefore potentiating the anesthetic effect after

administration of lidocaine.

Local anesthetics are prepared as salts, which are water soluble, and exist

simultaneously as uncharged base molecules and positively charged cations. The

Henderson-Hasselbalch equation [log(base/acid)=pH-pKa] shows that when the pH is equal to the pKa of the anesthetic, 50% of the drug exists in each form. Physiologic pH is

7.4, and while the tissues tend to maintain a normal pH, it takes longer to buffer a more acidic anesthetic solution. Solutions with a lower pH due to a vasoconstrictor (see

Discussion, page 78), such as lidocaine, may have a longer onset time while the tissues neutralize the solution to normal pH. Lidocaine, with a pKa of 7.9, has less available uncharged base-form molecules available to diffuse through the nerve sheath versus mepivacaine, with a pKa of 7.6. This may not only affect success of anesthesia, but may result in slower onset of lidocaine versus mepivacaine (20). McLean et al. (16) showed no difference in success or onset of anesthesia when comparing lidocaine and mepivacaine. The current study was done in the hope that this combination of anesthetics might have a synergistic effect and result in increased pulpal anesthesia success rates

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with the IANB. Rood and coauthors (17) reported on the potential benefits of using

prilocaine and lidocaine in combination, but it was determined that there was no

potentiation of the anesthetic effect.

In our study, anesthetic success was defined as the first of two consecutive 80/80

readings within the first five testing periods (17 minutes post-injection), with the 80/80 reading sustained through the remainder of the 56-minute testing period. All subjects were required to have profound lip numbness within 15 minutes of receiving the second

IANB injection. The absence of lip numbness indicated a failed IANB, and this occurred in six subjects who were reappointed. It is important to note that these six subjects all had profound lip numbness at their other two appointments. The pH of each solution was measured as follows: 6.69 (mepivacaine) and 4.28 (lidocaine) (Table A-16).

Success rates for mepivacaine/lidocaine and lidocaine/lidocaine, respectively, were as follows: second molar (51.5%, 56.6%), first molar (44.0%, 40.0%), second premolar (44.7%, 40.4%), first premolar (52.6%, 49.5%), lateral incisor (30.0%, 27.0%), and central incisor (10.1%, 10.0%) (Table A-6, Figures 1-6). No significant differences were noted between the two anesthetic groups for any tooth. It should be noted that direct comparisons to the control group can only be made by the referenced studies that utilized

3.6 mL of 2% lidocaine with 1:100,000 epinephrine and used the same definition of success as the current study (55, 67, 69, 83, 92). Our success rates are slightly lower than those of previous studies, but fairly similar to results by Nist et al. (69). This may be due to the population sampled. Unfortunately, no improvement of pulpal anesthetic success was found with the combination of mepivacaine and lidocaine.

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Factors that may influence pulpal anesthetic success also include the speed of

injection (70), presence of a vasoconstrictor (20), volume or concentration of anesthetic

(1, 63, 83, 94), additives to the solution (55, 79, 90, 93, 96), accuracy of the injection (56,

86, 91), and anesthetic type (16, 88, 89). Kanaa et al. (70) found that total pulpal anesthesia was greater in subjects receiving the IANB over 60 seconds versus 15 seconds in asymptomatic subjects. They suggest this is due to deeper penetration of the nerve trunk by the anesthetic with a slow injection as discussed by Rucci et al. (136).

The presence of a vasoconstrictor may affect anesthetic success. An IANB injection of 2% lidocaine without a vasoconstrictor may only last for 10-20 minutes (20); when 1:100,000 epinephrine is added, the duration of pulpal anesthesia is likely to be greater than 60 minutes (16, 55, 56, 63, 67, 69, 78-83, 85-95, 97). With the definition used in this study, shorter duration of an anesthetic without a vasoconstrictor would most likely cause it to be classified as a failure. Anesthetics such as mepivacaine and prilocaine have less vasodilatory effects; therefore, a vasoconstrictor is not needed to extend the duration of these drugs (20). The concentration of vasoconstrictor does not appear to affect pulpal anesthetic success. Wali et al. (94), Yared and Dagher (83), and

Dagher et al. (82) all showed no difference in success when altering the concentration of epinephrine in a lidocaine solution for the IANB.

It has been suggested that increasing the volume or concentration of anesthetic administered may increase the success of pulpal anesthesia with the IANB injection (1,

63, 83, 94). Studies have shown success rates utilizing 3.6 mL 2% lidocaine with

1:100,000 epinephrine ranging over the following percentages: second molar 50-87%,

89 first molar 43-77%, second premolar 52-90%, first premolar 56-80%, lateral incisor 25-

67%, and central incisor 10-39% (55, 63, 67, 69, 83, 85, 87, 92) (Table A-17). In studies utilizing 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, success ranged from: second molar 45-92%, first molar 32-85%, second premolar 29-92%, first premolar 42-

90%, lateral incisor 14-65%, and central incisor 2-38% (16, 56, 63, 78-82, 84, 86, 88-91,

93-95) (Table A-17). A retrospective evaluation of these studies by Nusstein (1) showed no difference in pulpal anesthetic success related to the volume of the anesthetic solution deposited. Although a retrospective evaluation by Yared and Dagher (83) showed higher pulpal anesthesia success rates with a greater volume of anesthetic, this trend was not seen in studies by Vreeland et al. (63) and Wali et al. (94). Therefore, it is assumed that volume of anesthetic solution does not influence pulpal anesthetic success. In the current study it was decided to use 3.6 mL of lidocaine because clinicians combining mepivacaine and lidocaine would use 1.8 mL cartridges of these anesthetics (resulting in a total volume of 3.6 mL), and by utilizing 3.6 mL of lidocaine the volume of the control group and experimental group were the same.

Other studies aiming to increase the success of the IANB have included using lidocaine hydrocarbonate (79), changing the concentration of epinephrine in the anesthetic (82, 83, 94), using a higher concentration of anesthetic (63), adding meperidine

(90) or diphenhydramine (93), buffering the anesthetic solution with sodium bicarbonate

(55), and a frequency-dependent conduction blockade (95). Unfortunately, none of these methods has increased the success of the IANB. Wolf et al. (96) attempted to increase success of the IANB with the utilization of mannitol. Mannitol is a six-carbon sugar

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alcohol that opens the perineural membrane and is commonly used in medicine to enable

chemotherapeutic agents to cross the blood-brain barrier (137). The addition of mannitol

to lidocaine was shown to increase total pulpal anesthesia 9-16%, but this method is

clinically impractical to use and success was still not at an acceptable level (96).

Attempts to improve the accuracy of the IANB injection have included

ultrasound-guided placement (86), evaluation of needle bevel direction utilizing the directional and bi-directional techniques (91), and the use of a peripheral nerve stimulator

(56). These studies showed that even with an accurate injection, the IANB success rate did not improve over the conventional technique. This may be because anesthetic solutions move in the path of least resistance, and even if the anesthetic is deposited in the pterygomandibular space it may move away from the nerve (15, 138, 139).

Supplemental injections such as the incisive nerve block (69), PDL (80), intraosseous

(81, 84), mylohyoid (85), bilateral IANB (87), and buccal and lingual infiltrations (76,

92) have been studied in an attempt to improve the success of the IANB with mixed

success.

Different anesthetic solutions have been used for the IANB in an attempt to

increase the incidence of successful pulpal anesthesia. Mikesell et al. (88) evaluated the

anesthetic efficacy of articaine and lidocaine for the IANB injection and found no

significant difference between the two anesthetics. Fernandez et al. (89) compared

lidocaine and bupivacaine and found that lidocaine had higher success rates in all study

teeth except first molars. It has been shown that 3% mepivacaine is equivalent to 2%

lidocaine with 1:100,000 epinephrine in terms of anesthetic success with the IANB (16).

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The pulpal anesthetic success rates of previous studies utilizing mepivacaine or lidocaine in asymptomatic patients can be found in the Table A-17.

Figures 1-6 show the percentage of pulpal anesthesia throughout the 56-minute testing period. The curves on each figure are nearly identical when comparing the two anesthetic groups. Most teeth showed a dramatic increase in pulpal anesthesia through 17 minutes, then sustained anesthesia or gradually increased for the remainder of the testing period. Clinically, this indicates that both anesthetic groups behave similarly, and that if pulpal anesthesia is obtained it will likely be sustained for at least 56 minutes. Neither anesthetic combination in our study was able to provide successful pulpal anesthesia in all patients.

Anesthetic Onset

The onset of anesthesia is determined by the pKa of the anesthetic solution (20), and may be affected by the concentration of anesthetic, additives to the solution, or by utilizing a combination of drugs. When the pKa of a solution is close to physiologic pH of 7.4, a higher percentage of base form molecules are available to diffuse across the nerve sheath; therefore, the time to onset is dependent on the number of anesthetic molecules available. Theoretically, with a higher concentration of anesthetic, more base molecules should also be available to diffuse through the nerve sheath to bind at the receptor site in the and produce anesthesia. However, Vreeland et al. (63) found no difference in onset times between 2% lidocaine and 4% lidocaine solutions in the first molar and lateral incisor. McLean et al. (16) showed no difference between 4%

92 prilocaine, 3% mepivacaine, and 2% lidocaine solutions regarding mean onset time of pulpal anesthesia for any of the teeth tested. Therefore, anesthetic concentration may not be as critical of a factor.

It has been suggested that adjusting the pH of an anesthetic solution with sodium bicarbonate may result in faster onset of anesthesia (20). While this buffering technique has proven to have some success in medicine (140-142), it has yet to show a decrease in anesthetic onset times with the IANB. Whitcomb et al. (55) evaluated the time to anesthetic onset with buffered and non-buffered 2% lidocaine solutions and found no difference for any of the teeth tested. Mean onset times for pulpal anesthesia in previous

IANB studies on asymptomatic subjects can be found in Table 5-4:

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Author (anesthetic) Tooth Mean Onset (minutes) Steinkruger et al. (91) Second molar 5.3 ± 5.6, 3.9 ± 4.7 (2% lidocaine) First molar 8.8 ± 7.8, 9.2 ± 8.5 Second premolar 10.2 ± 11.5, 10.3 ± 10.0 First premolar 11.1 ± 10.0, 10.8 ± 9.7 Lateral incisor 17.1 ± 17.6, 13.0 ± 13.9 Central incisor 19.1 ± 11.1, 19.4 ± 14.0 Whitcomb et al. (55) Second molar 5 ± 6.6 (2% lidocaine) First molar 5 ± 6.0 Second premolar 7 ± 7.3 First premolar 7 ± 6.7 Lateral incisor 11 ± 6.3 Central incisor 12 ± 9.3 Fernandez et al. (89) Second molar 6.4 ± 1.09 (2% lidocaine) First molar 10.7 ± 2.17 Second premolar 8.1 ± 1.12 First premolar 7.7 ± 1.16 Lateral incisor 12.0 ± 1.75 McLean et al. (16) First molar 10.8 ± 2.0 (2% lidocaine) First premolar 11.8 ± 1.9 Lateral incisor 17.2 ± 2.9 McLean et al. (16) First molar 8.2 ± 2.0 (3% mepivacaine) First premolar 10.0 ± 1.7 Lateral incisor 14.6 ± 3.3 Wali et al. (94) First molar 13.3 ± 2.7 (2% lidocaine) First premolar 12.5 ± 2.5 Lateral incisor 11.6 ± 2.8 Hinkley et al. (78) First molar 8.8 ± 1.8 (2% lidocaine) First premolar 10.6 ± 1.6 Lateral incisor 12.3 ± 1.9 Vreeland et al. (63) First molar 8.44 ± 1.85 (2% lidocaine) Lateral incisor 13.20 ± 2.35 Kanaa et al. (76) First molar 6.8 ± 5.8 (2% lidocaine) Premolars 8.9 ± 7.9 Lateral incisors 10.9 ± 11.3

Table 5-4. Mean onset times for pulpal anesthesia of IANB.

The current study hypothesized that there may be a faster time to onset with the combination of anesthetics due to the lower pKa and higher concentration of mepivacaine, and that there may be some potentiation of lidocaine when given as a second injection. The pH of each solution was measured and found to be the following:

6.69 (mepivacaine), and 4.28 (lidocaine) (Table A-16). In our study, mean times for onset

94 of anesthesia (in minutes) for mepivacaine/lidocaine and lidocaine/lidocaine, respectively, were the following: second molar (6.9 ±8.9, 6.0 ± 8.2), first molar (8.1 ±

8.3, 7.6 ± 10.0), second premolar (8.1 ± 7.6, 10.8 ± 11.2), first premolar (10.3 ± 11.5, 9.4

± 8.6), lateral incisor (10.2 ± 10.8, 12.2 ± 10.7), central incisor (16.2 ± 14.7, 12.2 ± 8.9)

(Table A-14). These times are very similar to onset times in the previously reviewed studies. No improvement was noted with the mepivacaine/lidocaine combination. No significant differences were seen between the two anesthetic groups. One weakness of our study is that onset times could only be calculated according to the testing time periods (4-minute intervals). This allows for large standard deviations and a much less accurate determination of time to onset of pulpal anesthesia. Ideally, onset time could be measured more accurately by testing the same tooth every 30 seconds, but this would result in data for only that tooth and this method would be impractical in a research setting.

Anesthetic Duration

The mean anesthetic duration times ranged from 35.2-44.5 minutes in our study

(Table A-15). However, these numbers do not reflect an accurate model in determining anesthetic duration. They only take into account the subjects who achieved anesthetic onset, and measured anesthesia only through the 56-minute testing period. Peak incidence of anesthesia ranged from 17-53 minutes with mepivacaine/lidocaine, and 25-53 minutes with lidocaine/lidocaine (Tables A-8 through A-13, Figures 1-6). In general, anterior teeth had a later peak incidence of anesthesia. Fernandez et al. (89) evaluated the

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anesthetic duration of 1.8 mL 2% lidocaine with 1:100,000 epinephrine and found that

pulpal anesthesia decreased the most between 2 and 2.5 hours. Most of the other

reviewed studies (16, 55, 56, 63, 67, 69, 78-83, 85-88, 90-95, 97) also measured pulpal anesthesia only for 50-60 minutes, as success is commonly defined within these parameters.

Factors that may influence anesthetic duration include volume of anesthetic, type of anesthetic, and additives to the solution. While maxillary anesthetic studies have shown increased duration of anesthesia with a greater volume of anesthetic (143-145), no one has evaluated the effect of volume on duration of anesthesia in the mandible. This may be due to the fact that duration of anesthesia generally tends to be longer in the mandible versus the maxilla (15), so this is not a common clinical problem. In other words, most patients who obtain pulpal anesthesia are able to sustain it for the remainder of the procedure. Short duration of anesthesia will be discussed later. More research could be done to compare the relationship of anesthetic volume to duration with the

IANB.

Long-acting anesthetics can greatly increase the duration of pulpal anesthesia.

Fernandez et al. (89) showed that bupivacaine had a significantly longer duration than

lidocaine when used for the IANB. Success rates within the first hour, however, were

significantly higher with lidocaine. Malamed (20) has suggested that a hydrocarbonated solution should provide a longer duration of anesthesia, as the intracellular pH is decreased by CO2 and the charged cation form of the anesthetic is “trapped” within the

nerve trunk. Chaney et al. (79) showed no difference in onset or peak incidence of

96 anesthesia in the first molar and first premolar when comparing lidocaine hydrocarbonate and lidocaine hydrochloride solutions, but since testing was stopped at 60 minutes postinjection it is impossible to evaluate the full duration of the anesthetics in this study.

Mepivacaine has only mild vasodilating properties and therefore can provide longer duration of anesthesia than most other local anesthetics without the addition of a vasoconstrictor (20). No significant differences in duration were found between 3% mepivacaine and 2% lidocaine with 1:100,000 epinephrine in the current study (Table

15).

Anesthetic Failure

Anesthetic failure was defined as the absence of two consecutive 80/80 readings during the testing period. Previous studies utilizing lidocaine or mepivacaine have shown the failure rates that can be found in Table A-18.

In the current study, anesthetic failure was observed in mepivacaine/lidocaine and lidocaine/lidocaine groups at the following rates: second molar (13.1%, 12.1%), first molar (30.0%, 28.0%), second premolar (22.6%, 26.9%), first premolar (13.4%, 21.6%), lateral incisor (52.0%, 54.0%), and central incisor (72.0%, 75.0%) (Table A-7). With the exception of the premolars, failure seemed to increase from posterior to anterior. It should be noted that direct comparisons to the control group can only be made by the referenced studies that utilized 3.6 mL of 2% lidocaine with 1:100,000 epinephrine (69,

83, 85). The failure rates in this study are consistent with previous studies using mepivacaine or lidocaine, and the combination of the two anesthetic solutions did not

97 decrease the failure rate for any of the teeth tested. Reasons for anesthetic failure can be found later in this discussion.

Subsets of failure include slow onset of anesthesia, non-continuous anesthesia, and anesthesia of short duration. These are problems occasionally encountered clinically, and as a result, they have been defined and evaluated during anesthetic studies. Slow onset of anesthesia is considered to occur when the subject experiences the onset of pulpal anesthesia (two consecutive 80 readings) greater than 15 minutes post-injection.

The incidence of slow onset anesthesia in asymptomatic subjects following the IANB, as found in previous studies, can be seen below:

Author Anesthetic Tooth Incidence (%) Mikesell et al. (88) 2% lidocaine Second molar 14% First molar 19% Second premolar 16% First premolar 23% Lateral incisor 19% Central incisor 16% McLean et al. (16) 2% lidocaine First molar 13% First premolar 23% Lateral incisor 30% McLean et al. (16) 3% mepivacaine First molar 17% First premolar 20% Lateral incisor 20% Nusstein et al. (1) 2% lidocaine First molar 19-22% First premolar 19-27% Lateral incisor 22-27% Hinkley et al. (78) 2% lidocaine First molar 11% First premolar 21% Lateral incisor 14% Dagher et al. (82) 2% lidocaine First molar 10% First premolar 17% Lateral incisor 23% Yared et al. (83) 2% lidocaine First molar 17% First premolar 3% Lateral incisor 10% Vreeland et al. (63) 2% lidocaine First molar 3.3% Lateral incisor 16.7%

Table 5-5. Incidence of anesthesia of slow onset for IANB. 98

The current study found the following percentages of anesthesia of slow onset utilizing mepivacaine/lidocaine and lidocaine/lidocaine, respectively: second molars

(12.8%, 14.0%), first molars (20.3%, 18.3%), second premolars (20.5%, 29.0%), first premolars (22.9%, 18.7%), lateral incisors (22.4%, 36.2%), central incisors (32.1%,

46.2%). Slow onset of anesthesia was seen more frequently in anterior versus posterior teeth, with no difference found between the two anesthetic groups. Our results were similar to those of previous studies in the posterior teeth, although we found a higher incidence of slow onset in lateral and central incisors. This may be due to the population sampled.

Non-continuous anesthesia is considered to occur when onset of pulpal anesthesia is achieved within 15 minutes, but the 80 reading is lost and then regained during the testing period. The incidence of non-continuous anesthesia in asymptomatic subjects, as found in previous IANB studies, can be seen below:

Author Anesthetic Tooth Incidence (%) McLean et al. (16) 2% Lidocaine First molar 20% First premolar 3% Lateral incisor 10% McLean et al. (16) 3% Mepivacaine First molar 30% First premolar 20% Lateral incisor 17% Nusstein et al. (1) 2% Lidocaine First molar 20% First premolar 8-12% Lateral incisor 13-15% Dagher et al. (82) 2% Lidocaine First molar 20% First premolar 27% Lateral incisor 27% Yared et al. (83) 2% Lidocaine First molar 0% First premolar 0% Lateral incisor 0% Vreeland et al. (63) 2% Lidocaine First molar 20.0% Lateral incisor 10.0%

Table 5-6. Incidence of non-continuous anesthesia for IANB. 99

The incidence of non-continuous anesthesia in our study was found in the

following percentages when utilizing mepivacaine/lidocaine and lidocaine/lidocaine,

respectively: second molar (26.7%, 19.8%), first molar (18.8%, 29.6%), second premolar

(24.7%, 26.1%), first premolar (22.9%, 22.7%), lateral incisor (18.4%, 25.5%), central

incisor (39.3%, 30.8%). No significant differences were noted between the two anesthetic

groups, although the incidence of non-continuous anesthesia is slightly higher in our study as compared to previous studies. This could be due to the population sampled.

Anesthesia is of short duration if the subject achieves two consecutive 80

readings, but loses the 80 reading prior to the end of testing (60 minutes) and it is not

regained during the testing period. Previous studies have shown the following incidence

of anesthesia of short duration in asymptomatic subjects with the IANB:

Author Anesthetic Volume Tooth Incidence (%) McLean et al. (16) 2% lidocaine 1.8 mL First molar 10% First premolar 7% Lateral incisor 0% McLean et al.(16) 3% mepivacaine 1.8 mL First molar 17% First premolar 17% Lateral incisor 17% Nusstein et al. (1) 2% lidocaine 1.8-3.6 mL First molar 8-12% First premolar 6-7% Lateral incisor 7-8% Hinkley et al. (78) 2% lidocaine 1.8 mL First molar 4% First premolar 4% Lateral incisor 0% Dagher et al. (82) 2% lidocaine 1.8 mL First molar 13% First premolar 20% Lateral incisor 17% Yared et al. (83) 2% lidocaine 3.6 mL First molar 10% First premolar 20% Lateral incisor 10% Vreeland et al. (63) 2% lidocaine 1.8 mL First molar 3.3% Lateral incisor 10.0%

Table 5-7. Incidence of anesthesia of short duration with IANB.

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Our study found the following incidence of anesthesia of short duration when utilizing mepivacaine/lidocaine and lidocaine/lidocaine, respectively: second molar

(18.6%, 23.3%), first molar (21.7%, 18.3%), second premolar (13.7%, 8.7%), first premolar (12.0%, 5.3%), lateral incisor (18.4%, 6.4%), central incisor (32.1%, 3.8%). No significant differences were noted between the two anesthetic groups; however, with the exception of the second molar, the incidence of anesthesia of short duration was higher in the mepivacaine/lidocaine group for all other teeth. Both groups have a high incidence of anesthesia of short duration when comparing to previous studies; this may be due to the population sampled.

While the cause of anesthetic failure remains undetermined, there are several hypotheses as to why this phenomenon occurs. Traditionally, it has been assumed that anatomic variation has led to inadequate nerve blockade (100); however, Hannan et al.

(86), Simon et al. (56), and Steinkruger et al. (91) have shown that even an accurate injection can result in failure of pulpal anesthesia. Another theory is that accessory nerve innervation may prevent mandibular pulpal anesthesia when only the inferior alveolar nerve is blocked. The chief nerve that is considered or blamed is the mylohyoid nerve which branches from the inferior alveolar nerve prior to its entry into the mandibular canal. The mylohyoid nerve runs downward and along the mylohyoid groove on the medial surface of the ramus (20). A study by Clark et al. (85) showed no improvement in pulpal anesthesia when adding a mylohyoid nerve block to the IANB. Also implicated is the retromolar canal, which may contain accessory innervation to the mandibular teeth.

Von Arx et al. (101) recently showed a 25% incidence of this canal that branches off 101 from the mandibular canal behind the third molar and travels to the retromolar foramen in the retromolar fossa. No study has looked at giving a supplemental injection to anesthetize this nerve. Failure and low success rates in mandibular anterior teeth have been associated with inferior alveolar nerve cross-innervation. Yonchak et al. (87) attempted to achieve pulpal anesthesia in mandibular anterior teeth utilizing bilateral mandibular blocks, and although this technique was slightly more successful than a unilateral block, anesthetic failure was still observed in mandibular incisors.

The effects of pH have been blamed for anesthetic failure. Solutions with a lower pH generally have fewer base molecules available to diffuse through the nerve sheath, which may result in slower onset and lower success rates. Buffering an anesthetic with sodium bicarbonate or using a hydrocarbonated solution causes CO2 to enter the cell and decrease intracellular pH, which favors the passage of the ionized form of an anesthetic to pass through the cell membrane (20). Whitcomb et al. (55) and Chaney et al. (79) studied these theories in asymptomatic patients, but no difference was seen in anesthetic success using buffered or hydrocarbonated anesthetics for the IANB injection, and anesthetic failure was significantly greater in hydrocarbonated solutions lacking epinephrine (79).

Perhaps the more widely accepted theory for anesthetic failure in asymptomatic patients is the central core theory. This theory states that the fibers on the outside of the nerve bundle, which are the first to be anesthetized, supply the molars while the fibers in the center of the nerve bundle, which are the last to be anesthetized, supply the anterior

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teeth (15, 24, 102). While this theory may explain higher experimental failure rates in

anterior teeth, it does not address anesthetic failure in molars or premolars (15).

Although our study was unable to find an improvement of anesthetic success with the combination of mepivacaine and lidocaine for the IANB, it is clear that more research needs to be done in this area. The IANB is the most frequently administered mandibular injection (20), and it is imperative that we improve success rates if our aim is to provide painless dentistry. Until we find a method to do so, supplemental injections such as the periodontal ligament injection (80), intraosseous injection (81, 84), and mandibular buccal infiltration injection (76, 92) currently seem to be the best way to achieve pulpal anesthesia when used in combination with the IANB.

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SUMMARY AND CONCLUSIONS

The purpose of this prospective, randomized, double-blind study was to compare the degree of pulpal anesthesia obtained with a combination 3% mepivacaine/2% lidocaine with 1:100,000 epinephrine formulation versus 2% lidocaine with 1:100,000 epinephrine/2% lidocaine with 1:100,000 epinephrine formulation in inferior alveolar nerve (IAN) blocks, and to study the injection pain of the two sets of IAN blocks.

One hundred asymptomatic subjects (50 males, 50 females) volunteered to participate in this study. The experimental teeth tested were mandibular first and second molars, first and second premolars, and lateral and central incisors. Prior to injection, pulp vitality was confirmed with an electric pulp tester (EPT). Subjects were instructed to report the pain of needle insertion, needle placement, and solution deposition on a Heft-

Parker VAS form.

Inferior alveolar nerve block (IANB) injections of 1.8 mL 3% mepivacaine plus

1.8 mL 2% lidocaine with 1:100,000 epinephrine and two injections of 1.8 mL 2% lidocaine with 1:100,000 epinephrine were administered at two separate appointments spaced at least one week apart. The experimental teeth were pulp tested every 4 minutes for 56 minutes post-injection. No subject response at maximum output of the EPT (80 reading) was the criterion for pulpal anesthesia. Anesthesia was considered successful when the subject achieved two consecutive 80 readings within 17 minutes post-injection

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and continuously sustained the 80 reading for the remainder of the testing period. The pH

of each anesthetic solution was also measured.

Mean injection pain scores for the first injection were in the mild pain range, with

the exception of needle placement pain in females, which was rated as moderate. No

significant differences in needle insertion and needle placement pain were noted between

the anesthetic groups. While a significant pH difference was found between the two

anesthetic solutions (p<0.0001), no significant difference in solution deposition pain was

seen between the two groups (p>0.05). No statistical analysis of the second injection was

completed, although injection pain was noted to be less than during the first injection.

Anesthetic success was not significantly different between the anesthetic groups in any of the teeth tested. The combination of 1.8 mL 3% mepivacaine and 1.8 mL 2% lidocaine

with 1:100,000 epinephrine is not different than two injections of 1.8 mL 2% lidocaine

with 1:100,000 epinephrine in regard to injection pain and pulpal anesthetic success for

the IANB.

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APPENDIX A

TABLES

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# of Age range Mean age Standard

subjects (years) (years) Deviation

Males 50 21-32 25.8 ±2.53 Females 50 18-38 25.4 ±3.60 Total 100 18-38 25.6 ±3.10

Table A-1. Biographical data for all subjects.

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Mepivacaine/ Lidocaine/ Needle Insertion p-value* p-adj‡ Lidocaine Lidocaine Total (N=100) 42.7 ± 24.1 43.5 ± 24.2

Male (N=50) 39.3 ± 23.4 37.6 ± 18.3 0.9060 1.0000 Female (N=50) 46.0 ± 24.5 49.3 ± 27.8 0.4003 0.8006 p-value† 0.1281 0.0227

p-value adj‡ 0.2013 0.0909

Needle Placement

Total (N=100) 55.6 ± 28.9 57.1 ± 28.2

Male (N=50) 48.7 ± 26.1 50.5 ± 26.9 0.6893 1.0000 Female (N=50) 62.4 ± 30.3 63.8 ± 28.1 0.6859 0.8006 p-value† 0.0438 0.0161

p-value adj‡ 0.1315 0.0804

Solution Deposition

Total (N=100) 41.2 ± 27.0 39.1 ± 24.7

Male (N=50) 29.1 ± 18.1 34.3 ± 22.3 0.0714 0.2143 Female (N=50) 53.2 ± 29.1 43.9 ± 26.3 0.0065 0.0194 p-value† <0.0001 0.1007

p-value adj‡ 0.0001 0.2013

† Multiple Mann-Whitney-Wilcoxon tests. * Multiple Wilcoxon matched-pairs, signed ranks tests. ‡ Corrected with step-down Bonferroni method of Holm x 6.

Table A-2. Mean pain ratings for first injection as measured on 170-mm VAS (in mm).

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Needle Mepivacaine/ Lidocaine/ Insertion Lidocaine Lidocaine Total (N=100) 24.4 ± 24.6 27.3 ± 23.8 Male (N=50) 22.2 ± 22.0 25.8 ± 25.5 Female (N=50) 26.6 ± 27.1 28.8 ± 22.1

Needle Placement Total (N=100) 21.6 ± 24.8 27.8 ± 27.1 Male (N=50) 20.6 ± 24.5 26.0 ± 27.1 Female (N=50) 22.6 ± 25.4 29.6 ± 27.3

Solution Deposition Total (N=100) 12.0 ± 18.5 16.7 ± 19.6 Male (N=50) 11.5 ± 15.7 16.3 ± 16.0 Female (N=50) 12.5 ± 21.0 17.1 ± 22.9

Table A-3. Mean pain ratings for second injection as measured on 170-mm VAS (in mm).

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None Mild Moderate Severe Mepivacaine/Lidocaine Female (N=50) Insertion 0 40 (80%) 9 (18%) 1 (2%) Placement 1 (2%) 27 (54%) 20 (40%) 2 (4%) Deposition 0 31 (62%) 19 (38%) 0 Male (N=50)

Insertion 0 43 (86%) 7 (14%) 0 Placement 1 (2%) 33 (66%) 16 (32%) 0 Deposition 3 (6%) 44 (88%) 3 (6%) 0 Lidocaine/Lidocaine

Female (N=50)

Insertion 1 (2%) 35 (70%) 12 (24%) 2 (4%) Placement 0 25 (50%) 23 (46%) 2 (4%) Deposition 0 39 (78%) 11 (22%) 0 Male (N=50)

Insertion 0 44 (88%) 6 (12%) 0 Placement 2 (4%) 35 (70%) 13 (26%) 0 Deposition 3 (6%) 42 (84%) 5 (10%) 0

Table A-4. Injection pain (first injection) utilizing 4-point scale.

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None Mild Moderate Severe Mepivacaine/Lidocaine Female (N=50) Insertion 12 (24%) 31 (62%) 7 (14%) 0 Placement 14 (28%) 32 (64%) 3 (6%) 1 (2%) Deposition 24 (48%) 23 (46%) 3 (6%) 0 Male (N=50)

Insertion 12 (24%) 35 (70%) 3 (6%) 0 Placement 16 (32%) 30 (60%) 4 (8%) 0 Deposition 22 (44%) 27 (54%) 1 (2%) 0 Lidocaine/Lidocaine

Female (N=50)

Insertion 9 (18%) 37 (74%) 4 (8%) 0 Placement 9 (18%) 34 (68%) 6 (12%) 1 (2%) Deposition 17 (34%) 31 (62%) 2 (4%) 0 Male (N=50)

Insertion 12 (24%) 33 (66%) 5 (10%) 0 Placement 14 (28%) 31 (62%) 5 (10%) 0 Deposition 15 (30%) 34 (68%) 1 (2%) 0

Table A-5. Injection pain (second injection) utilizing 4-point scale.

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Mepivacaine/ Lidocaine/ Tooth N p-value* p-adj† Lidocaine Lidocaine Second Molar 99 51 (51.5%) 56 (56.6%) 0.4869 1.0000 First Molar 100 44 (44.0%) 40 (40.0%) 0.5413 1.0000 Second Premolar 93 42 (44.7%) 38 (40.4%) 0.5413 1.0000 First Premolar 97 51 (52.6%) 48 (49.5%) 0.7283 1.0000 Lateral Incisor 100 30 (30.0%) 27 (27.0%) 0.6072 1.0000 Central Incisor 100 10 (10.1%) 10 (10.0%) 1.0000 1.0000

* Multiple McNemar tests. † Corrected with Step-down Bonferroni method of Holm.

Table A-6. Anesthetic success.

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Mepivacaine/ Lidocaine/ Tooth N p-value* p-adj† Lidocaine Lidocaine Second Molar 99 14 (13.1%) 13 (12.1%) 1.0000 1.0000 First Molar 100 30 (30.0%) 28 (28.0%) 0.8555 1.0000 Second Premolar 93 28 (22.6%) 32 (26.9%) 0.5235 1.0000 First Premolar 97 16 (13.4%) 24 (21.6%) 0.1153 1.0000 Lateral Incisor 100 52 (52.0%) 54 (54.0%) 0.8145 1.0000 Central Incisor 100 72 (72.0%) 75 (75.0%) 0.6072 1.0000

* Multiple McNemar tests. † Corrected with Step-down Bonferroni method of Holm.

Table A-7. Anesthetic failure.

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 6.0% 5.0% 0.7905 1.0000 5 12.0% 7.0% 0.0755 1.0000 9 14.0% 13.0% 0.8555 1.0000 13 17.0% 12.0% 0.0755 1.0000 17 18.0% 15.0% 0.3616 1.0000 21 19.0% 17.0% 0.5413 1.0000 25 19.0% 17.0% 0.4545 1.0000 29 16.0% 17.0% 0.8145 1.0000 33 17.0% 20.0% 0.2863 1.0000 37 22.0% 19.0% 0.3269 1.0000 41 20.0% 21.0% 0.8642 1.0000 45 21.0% 25.0% 0.2430 1.0000 49 22.0% 22.0% 1.0000 1.0000 53 21.0% 27.0% 0.0357 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-8. Central incisors 80/80 pulp tester readings (N=100).

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 8.0% 12.0% 0.1516 1.0000 5 26.0% 14.0% 0.0012 0.1004 9 34.0% 26.0% 0.0365 1.0000 13 37.0% 28.0% 0.0079 0.6491 17 41.0% 36.0% 0.1215 1.0000 21 38.0% 34.0% 0.2430 1.0000 25 41.0% 34.0% 0.0436 1.0000 29 42.0% 35.0% 0.0436 1.0000 33 41.0% 39.0% 0.5966 1.0000 37 37.0% 41.0% 0.2430 1.0000 41 40.0% 35.0% 0.1215 1.0000 45 42.0% 39.0% 0.3616 1.0000 49 42.0% 39.0% 0.3915 1.0000 53 41.0% 45.0% 0.2430 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-9. Lateral incisors 80/80 pulp tester readings (N=100).

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 17.5% 18.6% 0.8830 1.0000 5 45.4% 33.0% 0.0018 0.1529 9 51.5% 51.5% 1.0000 1.0000 13 62.9% 64.9% 0.6989 1.0000 17 74.2% 66.0% 0.0441 1.0000 21 74.2% 69.1% 0.2203 1.0000 25 71.1% 73.2% 0.6655 1.0000 29 75.3% 72.2% 0.4966 1.0000 33 74.2% 72.2% 0.6889 1.0000 37 76.3% 70.1% 0.1550 1.0000 41 74.2% 69.1% 0.2529 1.0000 45 75.3% 77.3% 0.6655 1.0000 49 78.4% 74.2% 0.3123 1.0000 53 77.3% 74.2% 0.4966 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-10. First premolars 80/80 pulp tester readings (N=97).

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 25.8% 24.7% 0.8957 1.0000 5 43.0% 34.4% 0.0441 1.0000 9 52.7% 51.6% 0.8877 1.0000 13 62.4% 51.6% 0.0135 1.0000 17 68.8% 59.1% 0.0154 1.0000 21 60.2% 63.4% 0.4966 1.0000 25 68.8% 65.6% 0.5118 1.0000 29 67.7% 66.7% 0.8957 1.0000 33 65.6% 64.5% 0.8957 1.0000 37 63.4% 67.7% 0.3497 1.0000 41 68.8% 67.7% 0.8957 1.0000 45 65.6% 71.0% 0.1839 1.0000 49 68.8% 68.8% 1.0000 1.0000 53 72.0% 68.8% 0.4966 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-11. Second premolars 80/80 pulp tester readings (N=93).

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 26.0% 26.0% 1.0000 1.0000 5 41.0% 50.0% 0.0356 1.0000 9 49.0% 47.0% 0.7080 1.0000 13 58.0% 55.0% 0.4966 1.0000 17 60.0% 57.0% 0.5258 1.0000 21 61.0% 55.0% 0.1550 1.0000 25 61.0% 63.0% 0.6989 1.0000 29 62.0% 61.0% 0.8919 1.0000 33 55.0% 63.0% 0.0681 1.0000 37 61.0% 60.0% 0.8957 1.0000 41 58.0% 57.0% 0.8957 1.0000 45 56.0% 62.0% 0.1409 1.0000 49 56.0% 59.0% 0.5118 1.0000 53 59.0% 65.0% 0.2067 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-12. First molars 80/80 pulp tester readings (N=100).

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Mepivacaine/ Lidocaine/ Time Lidocaine Lidocaine p-value† p-adj‡ (minutes) (%) (%) 1 51.5% 44.4% 0.1702 1.0000 5 61.6% 65.7% 0.4222 1.0000 9 68.7% 70.7% 0.7240 1.0000 13 71.7% 73.7% 0.6889 1.0000 17 77.8% 71.7% 0.0807 1.0000 21 73.7% 76.8% 0.4177 1.0000 25 74.7% 78.8% 0.3497 1.0000 29 73.7% 75.8% 0.6889 1.0000 33 74.7% 74.7% 1.0000 1.0000 37 74.7% 77.8% 0.4408 1.0000 41 74.7% 75.8% 0.8919 1.0000 45 73.7% 76.8% 0.4799 1.0000 49 66.7% 72.7% 0.1818 1.0000 53 72.7% 69.7% 0.5118 1.0000

† Multiple McNemar tests. ‡ Corrected with Step-down Bonferroni method of Holm.

Table A-13. Second molars 80/80 pulp tester readings (N=99).

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Mean Range Mepi/ Lido/ Mepi/ Lido/ N p-value† p-adj‡ Lido Lido Lido Lido Central incisor 19 16.2 ± 14.7 12.2 ± 8.9 1-45 1-33 0.4898 1.0000 Lateral incisor 38 10.2 ± 10.8 12.2 ± 10.7 1-49 1-49 0.1465 1.0000 First premolar 70 10.3 ± 11.5 9.4 ± 8.6 1-49 1-45 0.9413 1.0000 Second premolar 59 8.1 ± 7.6 10.8 ± 11.2 1-29 1-41 0.1175 1.0000 First molar 56 8.1 ± 8.3 7.6 ± 10.0 1-37 1-49 0.8207 1.0000 Second molar 78 6.9 ± 8.9 6.0 ± 8.2 1-41 1-41 0.3337 1.0000

† Multiple Wilcoxon matched-pairs, signed-ranks tests. ‡ Corrected with Step-down Bonferroni method of Holm. Mepi=Mepivacaine. Lido=Lidocaine.

Table A-14. Onset of anesthesia (minutes).

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Mean Range Mepi/ Lido/ Mepi/ Lido/ p- N p-adj‡ Lido Lido Lido Lido value† Central incisor 19 35.2 ± 16.3 40.8 ± 8.9 4-52 20-52 0.2980 1.0000 Lateral incisor 38 42.2 ± 11.1 40.9 ± 10.3 4-52 8-52 0.2679 1.0000 First premolar 70 41.5 ± 12.7 42.9 ± 9.7 4-52 4-52 0.6501 1.0000 Second premolar 59 43.3 ± 10.0 41.6 ± 11.8 4-52 4-52 0.3752 1.0000 First molar 56 42.6 ± 12.7 42.7 ± 12.3 4-52 4-52 0.8387 1.0000 Second molar 78 43.1 ± 12.9 44.5 ± 11.8 4-52 4-52 0.3706 1.0000

† Multiple Wilcoxon matched-pairs, signed-ranks tests. ‡ Corrected with Step-down Bonferroni method of Holm. Mepi=Mepivacaine. Lido=Lidocaine.

Table A-15. Duration of anesthesia (minutes).

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N Mean p-value M epivacaine 3 6.69 ± 0.06 Lidocaine 3 4.28 ± 0.16 <0.0001

Table A-16. pH of anesthetic solutions.

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2nd 1st 2nd 1st Lateral Central Study Solution Volume Molar Molar Premolar Premolar Incisor Incisor

Vreeland et al. (63) 2% lido 1.8 mL 63.30% 33.30% Hinkley et al. (78) 2% lido 1.8 mL 54% 50% 36% Chaney et al. (79) 2% lido 1.8 mL 57% 63% 43% Nist et al. (69) 2% lido 3.6 mL 50% 43% 52% 70% 35% 15% McLean et al. (16) 2% lido 1.8 mL 63% 67% 30% Childers et al. (80) 2% lido 1.8 mL 73% 63% 60% Dunbar et al. (81) 2% lido 1.8 mL 45% 42% 38% Dagher et al. (82) 2% lido 1.8 mL 47% 43% 50% Yared, Dagher (83) 2% lido 3.6 mL 77% 80% 67% Reitz et al.*(84) 2% lido 1.8 mL 74% 71% 60% Clark et al. *(85) 2% lido 3.6 mL 87% 73% 90% 87% 50% 33% Hannan et al.*(86) 2% lido 1.8 mL 92% 78-85% 90-92% 88-90% 65% 38% Yonchak et al.* (87) 2% lido 3.6 mL 50% 39% Mikesell et al. (88) 2% lido 1.8 mL 48% 32% 29% 42% 14% 2% Fernandez et al. (89) 2% lido 1.8 mL 77% 54% 74% 84% 54% Goodman et al. (90) 2% lido 1.8 mL 58% 44% 48% 51% 23% 8% Steinkruger et al. (91) 2% lido 1.8 mL 90-92% 73-76% 78% 73-80% 33-43% 14-24% Foster et al. (92) 2% lido 3.6 mL 74% 53% 66% 56% Goldberg et al. (67) 2% lido 3.6 mL 53% 62% 25% Willett et al. (93) 2% lido 1.8 mL 84% 52% 52% 68% 36% 12% Whitcomb et al. (55) 2% lido 3.6 mL 65% 58% 68% 71% 35% 10% Simon et al. (56) 2% lido 1.8 mL 45% 42% 32%

Wali et al. (94) 2% lido 1.8 mL 43% 60% 40% Hutchison et al. (95) 2% lido 1.8 mL 48-62% 18-35% Wolf et al.†(96) 2% lido 1.8 mL 75% 48% 54% 50% 27% McLean et al. (16) 3% mepi 1.8 mL 43% 57% 30% Guglielmo et al.* (97) 3% mepi 1.8 mL 90% 80% 77% Gallatin et al.* (98) 3% mepi 1.8 mL 81%

Stabile et al.* (99) 3% mepi 1.8 mL 81%

*success = 2 consecutive 80 readings with EPT. †total pulpal anesthesia.

Table A-17. Pulpal anesthesia success rates with 2% lidocaine with 1:100,000 epinephrine and with 3% mepivacaine for IANB.

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2nd 1st 2nd 1st Lateral Central Study Solution Volume Molar Molar Premolar Premolar Incisor Incisor

Vreeland et al. (63) 2% lido 1.8 mL 16.70% 33.30%

Hinkley et al. (78) 2% lido 1.8 mL 32% 25% 46%

Nist et al. (69) 2% lido 3.6 mL 22% 25% 30% 5% 45% 68% McLean et al. (16) 2% lido 1.8 mL 10% 10% 37%

Childers et al. (80) 2% lido 1.8 mL 15% 3% 8%

Dagher et al. (66) 2% lido 1.8 mL 10% 10% 27%

Yared, Dagher (83) 2% lido 3.6 mL 10% 3% 13%

Clark et al. (85) 2% lido 3.6 mL 13% 27% 10% 13% 50% 67% Hannan et al. (86) 2% lido 1.8 mL 8% 15-22% 8-10% 10-12% 35% 62% Mikesell et al. (88) 2% lido 1.8 mL 7% 18% 20% 19% 44% 72% McLean et al. (16) 3% mepi 1.8 mL 10% 0% 40%

Guglielmo et al. (97) 3% mepi 1.8 mL 10% 20% 23%

Gallatin et al. (98) 3% mepi 1.8 mL 19%

Stabile et al. (99) 3% mepi 1.8 mL 19%

Table A-18. Pulpal anesthesia failure rates with 2% lidocaine with 1:100,000 epinephrine and with 3% mepivacaine for IANB.

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APPENDIX B

FIGURES

125

100

90

80

70 Mepivacaine/Lidocaine 60 Lidocaine/Lidocaine 50

40

30 % Pulpal Anesthesia % Pulpal

20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 1. Percentage of pulpal anesthesia by time (minutes) for the central incisor.

126

100

90

80

Mepivacaine/Lidocaine 70 Lidocaine/Lidocaine 60

50

40

30 % Pulpal Anesthesia % Pulpal

20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 2. Percentage of pulpal anesthesia by time (minutes) for the lateral incisor.

127

100

90

80

70

60

50

40 Mepivacaine/Lidocaine 30 % Anesthesias Pulpal Lidocaine/Lidocaine 20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 3. Percentage of pulpal anesthesia by time (minutes) for the first premolar.

128

100

90

80

70

60

50

40 Mepivacaine/Lidocaine

% Anesthesia Pulpal 30 Lidocaine/Lidocaine 20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 4. Percentage of pulpal anesthesia by time (minutes) for the second premolar.

129

100

90

80

70

60

50

40 Mepivacaine/Lidocaine 30 % Anesthesia Pulpal Lidocaine/Lidocaine 20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 5. Percentage of pulpal anesthesia by time (minutes) for the first molar.

130

100

90

80

70

60

50 Mepivacaine/Lidocaine 40 Lidocaine/Lidocaine 30 % Anesthesia Pulpal 20

10

0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 Time (minutes)

Figure 6. Percentage of pulpal anesthesia by time (minutes) for the second molar.

131

APPENDIX C

MEDICAL HISTORY FORM

132

133

134

APPENDIX D

CONSENT FORM

135

The Ohio State University Consent to Participate in Research

A prospective, randomized, double-blind study of the Study Title: anesthetic efficacy of 3% mepivacaine plus 2% lidocaine with 1:100,000 epinephrine for inferior alveolar nerve blocks Principal John Nusstein, DDS, MS Investigator:

Sponsor:

• This is a consent form for research participation. It contains important information about this study and what to expect if you decide to participate. Please consider the information carefully. Feel free to discuss the study with your friends and family and to ask questions before making your decision whether or not to participate. • Your participation is voluntary. You may refuse to participate in this study. If you decide to take part in the study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your usual benefits. Your decision will not affect your future relationship with The Ohio State University. If you are a student or employee at Ohio State, your decision will not affect your grades or employment status. • You may or may not benefit as a result of participating in this study. Also, as explained below, your participation may result in unintended or harmful effects for you that may be minor or may be serious depending on the nature of the research. • You will be provided with any new information that develops during the study that may affect your decision whether or not to continue to participate. If you decide to participate, you will be asked to sign this form and will receive a copy of the form. You are being asked to consider participating in this study for the reasons explained below.

1. Why is this study being done? Lidocaine and mepivacaine are numbing solutions approved by the FDA for routine use in the dental office (like “novocaine”). The purpose of this study is to see if the combination of the two solutions is better at making your teeth numb for a dental procedure. This combination may also be less painful when you receive the injection (shot).

2. How many people will take part in this study? One hundred (100) people will take part in this study.

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3. What will happen if I take part in this study? You will receive injections (shots) of mepivacaine and lidocaine with epinephrine (numbing solutions like “novocaine”) in the back of your lower jaw. These numbing solutions are not experimental. They are routinely used in the dental office and have been approved by the FDA for dental use. Prior to the first injection, you will be required to complete a medical history questionnaire. A device called an electric pulp tester will be used to test your teeth for numbness. The electric pulp tester is a battery operated device that delivers a very small amount of current to the tooth resulting in a tingling sensation that might be uncomfortable or cause pain in the tooth being tested and which may last up to one second. It will be used on your teeth before the injections of numbing solution. Six of your lower teeth as well as a tooth on the opposite side (control tooth) will be tested with the electric pulp tester to be sure that your teeth respond (the nerves are alive and the teeth have not had root canal treatment). This will take about 6 minutes. You will have two appointments spaced at least two weeks apart. You will receive two injections (shots) at each appointment. After topical numbing anesthetic (20% Benzocaine), a gel that numbs the gum tissue, has been applied to the injection (shot) site for one minute, you will receive 1.8 mL (a little more than one third of a teaspoon) of either 3% mepivacaine or 2% lidocaine with 1:100,000 epinephrine. Whether you receive the mepivacaine or lidocaine will be determined at random (by chance, like flipping a coin). You will not know which injection you will receive. Your doctor will not know which injection you receive. You will then receive 1.8 mL 2% lidocaine with 1:100,000 epinephrine. Your teeth will be pulp tested every 4 minutes for a total of 60 minutes to determine how well the injection (shot) gets your teeth numb. In addition, the electric pulp tester will be used on one of your teeth on the opposite side (where you are not numb). Teeth that are not numb or are being used as a control will experience a tingling sensation or discomfort at which time the device will be removed immediately. You will be asked to rate the amount of pain you feel when the injections are being given. You will do this by marking your pain experience on a line graph with a pen.

4. How long will I be in the study? You are aware that you will have two appointments, each will last approximately 70 minutes - 10 minutes for baseline pulp testing and filling out health information and receiving the initial injection. Your teeth will be pulp tested for a total of 60 minutes.

5. Can I stop being in the study? You may leave the study at any time. If you decide to stop participating in the study, there will be no penalty to you, and you will not lose any benefits to which you are otherwise entitled. Your decision will not affect your future relationship with The Ohio State University.

If you are a student or staff member at OSU and choose not to participate in this study, your grades and/or employment will not be affected.

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6. What risks, side effects or discomforts can I expect from being in the study? You may have pain associated with the local anesthetic (numbing solution) or soreness at the site of the injections (shots) for approximately two days. Where you receive the injections, you may have swelling (hematoma-a collection of blood in my mouth) or a bruise may develop. You may experience a feeling of anxiety, lightheadedness or fainting, and or a temporary increase in your heart rate. The tingling sensation and/or slight discomfort (pain) produced by the pulp tester may be uncomfortable to you. You may have an allergic reaction to the local anesthetic (itching or hives, very rare), or have an unexpected infection (rare) which could result in permanent nerve damage. You may have soreness of your gum tissue for a few days or a possible altered sensation of your lip or tongue that may last up to a few weeks. Your tooth may feel sore to bite on for a few days.

If you are a woman able to have children, you will be questioned regarding pregnancy or suspected pregnancy and will not be allowed to participate if pregnant, suspect a pregnancy, trying to become pregnant, or nursing. Additionally, you will be required to take a urine pregnancy test before you can start this study. If you are a woman, you must also be using a reliable method of contraception (oral contraceptives, condoms, diaphragm, or abstinence) during the next 24 hours. The reason for excluding pregnant or potentially pregnant women is an attempt to minimize this population in the study because the potential risks to the fetus and nursing baby are unknown. There are no adequate and well-controlled studies of mepivacaine in pregnant women. This test will be paid for by the investigator.

7. What benefits can I expect from being in the study? You will not directly benefit from this study. Society may benefit if the combination of mepivacaine and lidocaine is better at making your teeth numb, and if the injections (shots) are less painful than with lidocaine alone.

8. What other choices do I have if I do not take part in the study? You may choose not to participate without penalty or loss of benefits to which you are otherwise entitled. If you are a student or staff member at OSU and choose not to participate in this study, your grades and/or employment will not be affected. There are no other choices other than to participate or not participate in the study.

9. Will my study-related information be kept confidential? Efforts will be made to keep your study-related information confidential. However, there may be circumstances where this information must be released. For example, personal information regarding your participation in this study may be disclosed if required by state law.

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Also, your records may be reviewed by the following groups (as applicable to the research): • Office for Human Research Protections or other federal, state, or international regulatory agencies; • U.S. Food and Drug Administration; • The Ohio State University Institutional Review Board or Office of Responsible Research Practices; • The sponsor supporting the study, their agents or study monitors; and • Your insurance company (if charges are billed to insurance).

You may also be asked to sign a separate Health Insurance Portability and Accountability Act (HIPAA) research authorization form if the study involves the use of your protected health information.

A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search the website at any time.

10. What are the costs of taking part in this study? The study will pay for the cost of the study drugs (mepivacaine and lidocaine) and the urine pregnancy test.

11. Will I be paid for taking part in this study? Yes, you will be paid $75 for your participation. You will receive $75.00 for completing all aspects of the study. If you are unable or unwilling to complete both sessions of the study, you will be paid a pro-rated $30.00 per session. Payment is to compensate you for time and travel expenses. By law, payments to subjects are considered taxable income.

12. What happens if I am injured because I took part in this study? If you suffer an injury from participating in this study, you should notify the researcher or study doctor immediately, who will determine if you should obtain medical treatment at The Ohio State University Medical Center.

The cost for this treatment will be billed to you or your medical or hospital insurance. The Ohio State University has no funds set aside for the payment of health care expenses for this study.

13. What are my rights if I take part in this study? If you choose to participate in the study, you may discontinue participation at any time without penalty or loss of benefits. By signing this form, you do not give up any personal legal rights you may have as a participant in this study.

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You will be provided with any new information that develops during the course of the research that may affect your decision whether or not to continue participation in the study.

You may refuse to participate in this study without penalty or loss of benefits to which you are otherwise entitled.

An Institutional Review Board responsible for human subjects research at The Ohio State University reviewed this research project and found it to be acceptable, according to applicable state and federal regulations and University policies designed to protect the rights and welfare of participants in research.

14. Who can answer my questions about the study? For questions, concerns, or complaints about the study you may contact Dr. John Nusstein or Dr. Emily Lammers at 614 – 292-5399.

For questions about your rights as a participant in this study or to discuss other study- related concerns or complaints with someone who is not part of the research team, you may contact Ms. Sandra Meadows in the Office of Responsible Research Practices at 1- 800-678-6251.

If you are injured as a result of participating in this study or for questions about a study- related injury, you may contact Dr. John Nusstein or Dr. Emily Lammers at 614 – 292- 5399.

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Signing the consent form

I have read (or someone has read to me) this form and I am aware that I am being asked to participate in a research study. I have had the opportunity to ask questions and have had them answered to my satisfaction. I voluntarily agree to participate in this study.

I am not giving up any legal rights by signing this form. I will be given a copy of this form.

Printed name of subject Signature of subject

AM/PM Date and time

Printed name of person authorized to consent for Signature of person authorized to consent for subject subject (when applicable) (when applicable)

AM/PM Relationship to the subject Date and time

Investigator/Research Staff

I have explained the research to the participant or his/her representative before requesting the signature(s) above. There are no blanks in this document. A copy of this form has been given to the participant or his/her representative.

Printed name of person obtaining consent Signature of person obtaining consent

AM/PM Date and time

Witness(es) - May be left blank if not required by the IRB

Printed name of witness Signature of witness

AM/PM Date and time

Printed name of witness Signature of witness

AM/PM Date and time 141

APPENDIX E

HIPAA PRIVACY FORM

142

THE OHIO STATE UNIVERSITY AUTHORIZATION TO USE PERSONAL HEALTH INFORMATION IN RESEARCH

Title of the Study: A prospective, randomized, double-blind study of the anesthetic efficacy of 3% mepivacaine plus 2% lidocaine with 1:100,000 epinephrine for inferior alveolar nerve blocks

OSU Protocol Number: 2012H0001

Principal Investigator: Dr. John Nusstein, DDS, MS

Subject Name______

Before researchers use or share any health information about you as part of this study, The Ohio State University is required to obtain your authorization. This helps explain to you how this information will be used or shared with others involved in the study.

• The Ohio State University and its hospitals, clinics, health-care providers and researchers are required to protect the privacy of your health information. • You should have received a Notice of Privacy Practices when you received health care services here. If not, let us know and a copy will be given to you. Please carefully review this information. Ask if you have any questions or do not understand any parts of this notice. • If you agree to take part in this study your health information will be used and shared with others involved in this study. Also, any new health information about you that comes from tests or other parts of this study will be shared with those involved in this study. • Health information about you that will be used or shared with others involved in this study may include your research record and any health care records at the Ohio State University. For example, this may include your medical records, x-ray or laboratory results. Psychotherapy notes in your health records (if any) will not, however, be shared or used. Use of these notes requires a separate, signed authorization. Please read the information carefully before signing this form. Please ask if you have any questions about this authorization, the University’s Notice of Privacy Practices or the study before signing this form.

Initials/Date: ______

Page 1 of 3 143

Those Who May Use, Share And Receive Your Information As Part Of This Study

• Researchers and staff at The Ohio State University will use, share and receive your personal health information for this research study. Authorized Ohio State University staff not involved in the study may be aware that you are participating in a research study and have access to your information. If this study is related to your medical care, your study-related information may be placed in your permanent hospital, clinic or physician’s office records. • Those who oversee the study will have access to your information, including: • Members and staff of the Ohio State University’s Institutional Review Boards, including the Western Institutional Review Board • The Office for Responsible Research Practices • University data safety monitoring committees • The Ohio State University Research Foundation • Your health information may also be shared with federal and state agencies that have oversight of the study or to whom access is required under the law. These may include: • The Food and Drug Administration • The Office for Human Research Protections • The National Institutes of Health • The Ohio Department of Job and Family Services

These researchers, companies and/or organization(s) outside of The Ohio State University may also use, share and receive your health information in connection with this study:

• None

The information that is shared with those listed above may no longer be protected by federal privacy rules.

Initials/Date______

Page 2 of 3

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Authorization Period This authorization will not expire unless you change your mind and revoke it in writing. There is no set date at which your information will be destroyed or no longer used. This is because the information used and created during the study may be analyzed for many years, and it is not possible to know when this will be complete. Signing the Authorization

• You have the right to refuse to sign this authorization. Your health care outside of the study, payment for your health care, and your health care benefits will not be affected if you choose not to sign this form. • You will not be able to take part in this study and will not receive any study treatments if you do not sign this form. • If you sign this authorization, you may change your mind at any time. Researchers may continue to use information collected up until the time that you formally changed your mind. If you change your mind, your authorization must be revoked in writing. To revoke your authorization, please write to: Dr. John Nusstein at the College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio 43210 or Dr. Henry Fischbach at the College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio 43210 • Signing this authorization also means that you will not be able to see or copy your study- related information until the study is completed. This includes any portion of your medical records that describes study treatment.

Contacts for Questions

• If you have any questions relating to your privacy rights, please contact Dr. Henry Fischbach at the College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio 43210. • If you have any questions relating to the research, please contact Dr. John Nusstein at the College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio 43210.

Signature

I have read (or someone has read to me) this form and have been able to ask questions. All of my questions about this form have been answered to my satisfaction. By signing below, I permit Dr. John Nusstein and the others listed on this form to use and share my personal health information for this study. I will be given a copy of this signed form.

Signature______(Subject or Legally Authorized Representative) Name ______(Print name above) (If legal representative, also print relationship to subject.) Date______Time ______AM / PM

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APPENDIX F

HEFT-PARKER VAS FORM

146

INJECTION INFORMATION SHEET

Name: ______Patient #: ______

Date: ______Side: ____

Code #: ______Injection # 1 or 2

Needle Insertion 1. When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during needle insertion.

None Faint Weak Mild Moderate Strong Intense Maximum Possible

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Needle Placement 2. When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during needle placement.

None Faint Weak Mild Moderate Strong Intense Maximum Possible

Solution Deposition 3. When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during solution deposition.

None Faint Weak Mild Moderate Strong Intense Maximum Possible

APPENDIX G

ELECTRIC PULP TESTING FORM

148

EPT Values

Date:______Patient # ______Side:______

Sex: M F Patient Age: ______

Contra- 2nd 1st 2nd 1st Lateral Central lateral molar molar premolar premolar incisor incisor canine Min. Pre-test

Min. Pre-test

Base-line * Indicates tooth will be tested with a mock electrode Contra- 2nd 1 st 2 nd 1st Lateral Central Numbness lateral Molar Molar Premolar Premolar Incisor Incisor Lip / Tongue Canine 1

2

3

4

5 Y N / Y N

6

7

8

9

10 Y N / Y N

11

12

13

14

15 Y N / Y N

16 149

17

18

19

20 * Y N / Y N

21

22

23

24

25 Y N / Y N

26

27

28

29

30 Y N / Y N

31

32

33

34

35 Y N / Y N

36 *

37

38

39

40 Y N / Y N 150

41

42

43

44

45 Y N / Y N

46

47

48 *

49

50 Y N / Y N

51

52

53

54

55 Y N / Y N

56

57

58

59

60 * Y N / Y N

151

APPENDIX H

RAW DATA

152

SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

1 24 1 0 37 53 19 0 1 24 1 0 37 53 19 0 1 24 1 0 37 53 19 0 1 24 1 0 37 53 19 0 1 24 1 0 37 53 19 0 1 24 1 0 37 53 19 0 2 28 0 1 115 85 53 37 2 28 0 1 115 85 53 37 2 28 0 1 115 85 53 37 2 28 0 1 115 85 53 37 2 28 0 1 115 85 53 37 2 28 0 1 115 85 53 37 3 27 0 1 83 54 54 0 3 27 0 1 83 54 54 0 3 27 0 1 83 54 54 0 3 27 0 1 83 54 54 0 3 27 0 1 83 54 54 0 3 27 0 1 83 54 54 0 4 23 0 0 21 20 22 21 4 23 0 0 21 20 22 21 4 23 0 0 21 20 22 21 4 23 0 0 21 20 22 21 4 23 0 0 21 20 22 21 4 23 0 0 21 20 22 21 5 26 0 1 24 24 32 15 5 26 0 1 24 24 32 15 5 26 0 1 24 24 32 15 5 26 0 1 24 24 32 15 5 26 0 1 24 24 32 15 5 26 0 1 24 24 32 15 6 26 1 0 59 87 52 58 6 26 1 0 59 87 52 58 6 26 1 0 59 87 52 58 6 26 1 0 59 87 52 58 6 26 1 0 59 87 52 58 6 26 1 0 59 87 52 58 7 24 1 0 37 54 54 0 7 24 1 0 37 54 54 0 7 24 1 0 37 54 54 0 7 24 1 0 37 54 54 0 7 24 1 0 37 54 54 0 7 24 1 0 37 54 54 0

153 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

8 26 1 1 15 24 5 0 8 26 1 1 15 24 5 0 8 26 1 1 15 24 5 0 8 26 1 1 15 24 5 0 8 26 1 1 15 24 5 0 8 26 1 1 15 24 5 0 9 24 0 1 21 54 21 21 9 24 0 1 21 54 21 21 9 24 0 1 21 54 21 21 9 24 0 1 21 54 21 21 9 24 0 1 21 54 21 21 9 24 0 1 21 54 21 21 10 24 0 0 30 95 95 68 10 24 0 0 30 95 95 68 10 24 0 0 30 95 95 68 10 24 0 0 30 95 95 68 10 24 0 0 30 95 95 68 10 24 0 0 30 95 95 68 11 25 0 0 54 83 37 21 11 25 0 0 54 83 37 21 11 25 0 0 54 83 37 21 11 25 0 0 54 83 37 21 11 25 0 0 54 83 37 21 11 25 0 0 54 83 37 21 12 27 1 1 37 37 37 0 12 27 1 1 37 37 37 0 12 27 1 1 37 37 37 0 12 27 1 1 37 37 37 0 12 27 1 1 37 37 37 0 12 27 1 1 37 37 37 0 13 25 0 0 37 54 54 0 13 25 0 0 37 54 54 0 13 25 0 0 37 54 54 0 13 25 0 0 37 54 54 0 13 25 0 0 37 54 54 0 13 25 0 0 37 54 54 0 14 27 0 1 57 79 62 51 14 27 0 1 57 79 62 51 14 27 0 1 57 79 62 51 14 27 0 1 57 79 62 51 14 27 0 1 57 79 62 51 14 27 0 1 57 79 62 51

154 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

15 24 1 1 21 54 21 21 15 24 1 1 21 54 21 21 15 24 1 1 21 54 21 21 15 24 1 1 21 54 21 21 15 24 1 1 21 54 21 21 15 24 1 1 21 54 21 21 16 29 1 0 37 37 37 0 16 29 1 0 37 37 37 0 16 29 1 0 37 37 37 0 16 29 1 0 37 37 37 0 16 29 1 0 37 37 37 0 16 29 1 0 37 37 37 0 17 26 1 1 50 90 56 63 17 26 1 1 50 90 56 63 17 26 1 1 50 90 56 63 17 26 1 1 50 90 56 63 17 26 1 1 50 90 56 63 17 26 1 1 50 90 56 63 18 25 1 0 21 0 37 0 18 25 1 0 21 0 37 0 18 25 1 0 21 0 37 0 18 25 1 0 21 0 37 0 18 25 1 0 21 0 37 0 18 25 1 0 21 0 37 0 19 28 1 0 41 52 52 11 19 28 1 0 41 52 52 11 19 28 1 0 41 52 52 11 19 28 1 0 41 52 52 11 19 28 1 0 41 52 52 11 19 28 1 0 41 52 52 11 20 29 1 1 38 54 38 53 20 29 1 1 38 54 38 53 20 29 1 1 38 54 38 53 20 29 1 1 38 54 38 53 20 29 1 1 38 54 38 53 20 29 1 1 38 54 38 53 21 29 1 0 37 54 54 3 21 29 1 0 37 54 54 3 21 29 1 0 37 54 54 3 21 29 1 0 37 54 54 3 21 29 1 0 37 54 54 3 21 29 1 0 37 54 54 3

155 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

22 23 1 1 14 45 29 15 22 23 1 1 14 45 29 15 22 23 1 1 14 45 29 15 22 23 1 1 14 45 29 15 22 23 1 1 14 45 29 15 22 23 1 1 14 45 29 15 23 23 1 1 37 83 37 37 23 23 1 1 37 83 37 37 23 23 1 1 37 83 37 37 23 23 1 1 37 83 37 37 23 23 1 1 37 83 37 37 23 23 1 1 37 83 37 37 24 29 1 0 83 83 21 21 24 29 1 0 83 83 21 21 24 29 1 0 83 83 21 21 24 29 1 0 83 83 21 21 24 29 1 0 83 83 21 21 24 29 1 0 83 83 21 21 25 24 0 1 69 65 27 31 25 24 0 1 69 65 27 31 25 24 0 1 69 65 27 31 25 24 0 1 69 65 27 31 25 24 0 1 69 65 27 31 25 24 0 1 69 65 27 31 26 25 1 0 45 60 30 0 26 25 1 0 45 60 30 0 26 25 1 0 45 60 30 0 26 25 1 0 45 60 30 0 26 25 1 0 45 60 30 0 26 25 1 0 45 60 30 0 27 23 1 0 54 83 0 37 27 23 1 0 54 83 0 37 27 23 1 0 54 83 0 37 27 23 1 0 54 83 0 37 27 23 1 0 54 83 0 37 27 23 1 0 54 83 0 37 28 24 0 1 37 54 54 21 28 24 0 1 37 54 54 21 28 24 0 1 37 54 54 21 28 24 0 1 37 54 54 21 28 24 0 1 37 54 54 21 28 24 0 1 37 54 54 21

156 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

29 24 0 0 54 74 54 75 29 24 0 0 54 74 54 75 29 24 0 0 54 74 54 75 29 24 0 0 54 74 54 75 29 24 0 0 54 74 54 75 29 24 0 0 54 74 54 75 30 27 1 1 17 100 109 26 30 27 1 1 17 100 109 26 30 27 1 1 17 100 109 26 30 27 1 1 17 100 109 26 30 27 1 1 17 100 109 26 30 27 1 1 17 100 109 26 31 26 0 1 60 78 58 77 31 26 0 1 60 78 58 77 31 26 0 1 60 78 58 77 31 26 0 1 60 78 58 77 31 26 0 1 60 78 58 77 31 26 0 1 60 78 58 77 32 22 1 0 21 37 54 0 32 22 1 0 21 37 54 0 32 22 1 0 21 37 54 0 32 22 1 0 21 37 54 0 32 22 1 0 21 37 54 0 32 22 1 0 21 37 54 0 33 31 1 1 6 26 42 0 33 31 1 1 6 26 42 0 33 31 1 1 6 26 42 0 33 31 1 1 6 26 42 0 33 31 1 1 6 26 42 0 33 31 1 1 6 26 42 0 34 24 0 0 54 83 37 21 34 24 0 0 54 83 37 21 34 24 0 0 54 83 37 21 34 24 0 0 54 83 37 21 34 24 0 0 54 83 37 21 34 24 0 0 54 83 37 21 35 24 1 0 29 52 47 3 35 24 1 0 29 52 47 3 35 24 1 0 29 52 47 3 35 24 1 0 29 52 47 3 35 24 1 0 29 52 47 3 35 24 1 0 29 52 47 3

157 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

36 29 1 1 54 54 83 54 36 29 1 1 54 54 83 54 36 29 1 1 54 54 83 54 36 29 1 1 54 54 83 54 36 29 1 1 54 54 83 54 36 29 1 1 54 54 83 54 37 23 0 0 32 35 25 5 37 23 0 0 32 35 25 5 37 23 0 0 32 35 25 5 37 23 0 0 32 35 25 5 37 23 0 0 32 35 25 5 37 23 0 0 32 35 25 5 38 25 0 1 54 21 21 21 38 25 0 1 54 21 21 21 38 25 0 1 54 21 21 21 38 25 0 1 54 21 21 21 38 25 0 1 54 21 21 21 38 25 0 1 54 21 21 21 39 26 0 1 54 83 83 54 39 26 0 1 54 83 83 54 39 26 0 1 54 83 83 54 39 26 0 1 54 83 83 54 39 26 0 1 54 83 83 54 39 26 0 1 54 83 83 54 40 37 0 0 54 54 54 0 40 37 0 0 54 54 54 0 40 37 0 0 54 54 54 0 40 37 0 0 54 54 54 0 40 37 0 0 54 54 54 0 40 37 0 0 54 54 54 0 41 24 0 1 5 73 21 0 41 24 0 1 5 73 21 0 41 24 0 1 5 73 21 0 41 24 0 1 5 73 21 0 41 24 0 1 5 73 21 0 41 24 0 1 5 73 21 0 42 24 1 0 34 42 29 29 42 24 1 0 34 42 29 29 42 24 1 0 34 42 29 29 42 24 1 0 34 42 29 29 42 24 1 0 34 42 29 29 42 24 1 0 34 42 29 29

158 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

43 23 0 0 21 54 39 0 43 23 0 0 21 54 39 0 43 23 0 0 21 54 39 0 43 23 0 0 21 54 39 0 43 23 0 0 21 54 39 0 43 23 0 0 21 54 39 0 44 23 0 1 83 114 21 83 44 23 0 1 83 114 21 83 44 23 0 1 83 114 21 83 44 23 0 1 83 114 21 83 44 23 0 1 83 114 21 83 44 23 0 1 83 114 21 83 45 27 0 0 142 142 113 54 45 27 0 0 142 142 113 54 45 27 0 0 142 142 113 54 45 27 0 0 142 142 113 54 45 27 0 0 142 142 113 54 45 27 0 0 142 142 113 54 46 25 0 1 37 54 21 54 46 25 0 1 37 54 21 54 46 25 0 1 37 54 21 54 46 25 0 1 37 54 21 54 46 25 0 1 37 54 21 54 46 25 0 1 37 54 21 54 47 22 0 1 9 12 23 16 47 22 0 1 9 12 23 16 47 22 0 1 9 12 23 16 47 22 0 1 9 12 23 16 47 22 0 1 9 12 23 16 47 22 0 1 9 12 23 16 48 24 1 0 37 37 37 37 48 24 1 0 37 37 37 37 48 24 1 0 37 37 37 37 48 24 1 0 37 37 37 37 48 24 1 0 37 37 37 37 48 24 1 0 37 37 37 37 49 25 1 1 27 39 21 7 49 25 1 1 27 39 21 7 49 25 1 1 27 39 21 7 49 25 1 1 27 39 21 7 49 25 1 1 27 39 21 7 49 25 1 1 27 39 21 7

159 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

50 24 0 0 41 119 88 40 50 24 0 0 41 119 88 40 50 24 0 0 41 119 88 40 50 24 0 0 41 119 88 40 50 24 0 0 41 119 88 40 50 24 0 0 41 119 88 40 51 27 1 0 54 83 54 83 51 27 1 0 54 83 54 83 51 27 1 0 54 83 54 83 51 27 1 0 54 83 54 83 51 27 1 0 54 83 54 83 51 27 1 0 54 83 54 83 52 28 1 1 21 0 0 21 52 28 1 1 21 0 0 21 52 28 1 1 21 0 0 21 52 28 1 1 21 0 0 21 52 28 1 1 21 0 0 21 52 28 1 1 21 0 0 21 53 32 0 0 52 77 57 35 53 32 0 0 52 77 57 35 53 32 0 0 52 77 57 35 53 32 0 0 52 77 57 35 53 32 0 0 52 77 57 35 53 32 0 0 52 77 57 35 54 24 0 1 30 68 29 12 54 24 0 1 30 68 29 12 54 24 0 1 30 68 29 12 54 24 0 1 30 68 29 12 54 24 0 1 30 68 29 12 54 24 0 1 30 68 29 12 55 34 0 1 54 83 37 0 55 34 0 1 54 83 37 0 55 34 0 1 54 83 37 0 55 34 0 1 54 83 37 0 55 34 0 1 54 83 37 0 55 34 0 1 54 83 37 0 56 26 0 0 21 21 21 0 56 26 0 0 21 21 21 0 56 26 0 0 21 21 21 0 56 26 0 0 21 21 21 0 56 26 0 0 21 21 21 0 56 26 0 0 21 21 21 0

160 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

57 24 1 1 37 41 4 21 57 24 1 1 37 41 4 21 57 24 1 1 37 41 4 21 57 24 1 1 37 41 4 21 57 24 1 1 37 41 4 21 57 24 1 1 37 41 4 21 58 25 0 0 0 113 83 0 58 25 0 0 0 113 83 0 58 25 0 0 0 113 83 0 58 25 0 0 0 113 83 0 58 25 0 0 0 113 83 0 58 25 0 0 0 113 83 0 59 30 1 0 58 50 28 19 59 30 1 0 58 50 28 19 59 30 1 0 58 50 28 19 59 30 1 0 58 50 28 19 59 30 1 0 58 50 28 19 59 30 1 0 58 50 28 19 60 26 1 1 21 21 9 12 60 26 1 1 21 21 9 12 60 26 1 1 21 21 9 12 60 26 1 1 21 21 9 12 60 26 1 1 21 21 9 12 60 26 1 1 21 21 9 12 61 25 1 0 87 40 3 35 61 25 1 0 87 40 3 35 61 25 1 0 87 40 3 35 61 25 1 0 87 40 3 35 61 25 1 0 87 40 3 35 61 25 1 0 87 40 3 35 62 27 0 1 21 79 13 17 62 27 0 1 21 79 13 17 62 27 0 1 21 79 13 17 62 27 0 1 21 79 13 17 62 27 0 1 21 79 13 17 62 27 0 1 21 79 13 17 63 30 1 1 60 42 42 35 63 30 1 1 60 42 42 35 63 30 1 1 60 42 42 35 63 30 1 1 60 42 42 35 63 30 1 1 60 42 42 35 63 30 1 1 60 42 42 35

161 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

64 25 1 0 54 37 21 21 64 25 1 0 54 37 21 21 64 25 1 0 54 37 21 21 64 25 1 0 54 37 21 21 64 25 1 0 54 37 21 21 64 25 1 0 54 37 21 21 65 28 0 1 35 48 6 11 65 28 0 1 35 48 6 11 65 28 0 1 35 48 6 11 65 28 0 1 35 48 6 11 65 28 0 1 35 48 6 11 65 28 0 1 35 48 6 11 66 26 0 0 37 54 83 21 66 26 0 0 37 54 83 21 66 26 0 0 37 54 83 21 66 26 0 0 37 54 83 21 66 26 0 0 37 54 83 21 66 26 0 0 37 54 83 21 67 24 0 0 53 83 54 37 67 24 0 0 53 83 54 37 67 24 0 0 53 83 54 37 67 24 0 0 53 83 54 37 67 24 0 0 53 83 54 37 67 24 0 0 53 83 54 37 68 24 1 1 21 37 21 19 68 24 1 1 21 37 21 19 68 24 1 1 21 37 21 19 68 24 1 1 21 37 21 19 68 24 1 1 21 37 21 19 68 24 1 1 21 37 21 19 69 23 1 0 30 26 10 17 69 23 1 0 30 26 10 17 69 23 1 0 30 26 10 17 69 23 1 0 30 26 10 17 69 23 1 0 30 26 10 17 69 23 1 0 30 26 10 17 70 25 0 1 21 83 83 21 70 25 0 1 21 83 83 21 70 25 0 1 21 83 83 21 70 25 0 1 21 83 83 21 70 25 0 1 21 83 83 21 70 25 0 1 21 83 83 21

162 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

71 20 0 1 83 83 54 54 71 20 0 1 83 83 54 54 71 20 0 1 83 83 54 54 71 20 0 1 83 83 54 54 71 20 0 1 83 83 54 54 71 20 0 1 83 83 54 54 72 24 1 0 21 37 68 22 72 24 1 0 21 37 68 22 72 24 1 0 21 37 68 22 72 24 1 0 21 37 68 22 72 24 1 0 21 37 68 22 72 24 1 0 21 37 68 22 73 23 0 1 21 37 37 0 73 23 0 1 21 37 37 0 73 23 0 1 21 37 37 0 73 23 0 1 21 37 37 0 73 23 0 1 21 37 37 0 73 23 0 1 21 37 37 0 74 24 1 0 54 83 37 54 74 24 1 0 54 83 37 54 74 24 1 0 54 83 37 54 74 24 1 0 54 83 37 54 74 24 1 0 54 83 37 54 74 24 1 0 54 83 37 54 75 24 1 0 83 113 0 54 75 24 1 0 83 113 0 54 75 24 1 0 83 113 0 54 75 24 1 0 83 113 0 54 75 24 1 0 83 113 0 54 75 24 1 0 83 113 0 54 76 30 1 1 11 3 3 16 76 30 1 1 11 3 3 16 76 30 1 1 11 3 3 16 76 30 1 1 11 3 3 16 76 30 1 1 11 3 3 16 76 30 1 1 11 3 3 16 77 29 0 0 70 66 36 35 77 29 0 0 70 66 36 35 77 29 0 0 70 66 36 35 77 29 0 0 70 66 36 35 77 29 0 0 70 66 36 35 77 29 0 0 70 66 36 35

163 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

78 21 1 1 23 32 59 18 78 21 1 1 23 32 59 18 78 21 1 1 23 32 59 18 78 21 1 1 23 32 59 18 78 21 1 1 23 32 59 18 78 21 1 1 23 32 59 18 79 24 0 1 66 54 46 50 79 24 0 1 66 54 46 50 79 24 0 1 66 54 46 50 79 24 0 1 66 54 46 50 79 24 0 1 66 54 46 50 79 24 0 1 66 54 46 50 80 22 0 0 51 59 27 25 80 22 0 0 51 59 27 25 80 22 0 0 51 59 27 25 80 22 0 0 51 59 27 25 80 22 0 0 51 59 27 25 80 22 0 0 51 59 27 25 81 25 1 1 21 54 21 39 81 25 1 1 21 54 21 39 81 25 1 1 21 54 21 39 81 25 1 1 21 54 21 39 81 25 1 1 21 54 21 39 81 25 1 1 21 54 21 39 82 32 1 0 54 83 37 114 82 32 1 0 54 83 37 114 82 32 1 0 54 83 37 114 82 32 1 0 54 83 37 114 82 32 1 0 54 83 37 114 82 32 1 0 54 83 37 114 83 23 0 0 83 54 21 21 83 23 0 0 83 54 21 21 83 23 0 0 83 54 21 21 83 23 0 0 83 54 21 21 83 23 0 0 83 54 21 21 83 23 0 0 83 54 21 21 84 22 0 1 54 37 21 54 84 22 0 1 54 37 21 54 84 22 0 1 54 37 21 54 84 22 0 1 54 37 21 54 84 22 0 1 54 37 21 54 84 22 0 1 54 37 21 54

164 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

85 24 1 0 37 83 54 83 85 24 1 0 37 83 54 83 85 24 1 0 37 83 54 83 85 24 1 0 37 83 54 83 85 24 1 0 37 83 54 83 85 24 1 0 37 83 54 83 86 23 1 1 21 21 54 37 86 23 1 1 21 21 54 37 86 23 1 1 21 21 54 37 86 23 1 1 21 21 54 37 86 23 1 1 21 21 54 37 86 23 1 1 21 21 54 37 87 23 0 1 61 49 31 42 87 23 0 1 61 49 31 42 87 23 0 1 61 49 31 42 87 23 0 1 61 49 31 42 87 23 0 1 61 49 31 42 87 23 0 1 61 49 31 42 88 24 1 0 37 54 37 0 88 24 1 0 37 54 37 0 88 24 1 0 37 54 37 0 88 24 1 0 37 54 37 0 88 24 1 0 37 54 37 0 88 24 1 0 37 54 37 0 89 27 1 1 21 21 21 21 89 27 1 1 21 21 21 21 89 27 1 1 21 21 21 21 89 27 1 1 21 21 21 21 89 27 1 1 21 21 21 21 89 27 1 1 21 21 21 21 90 25 0 0 114 114 114 37 90 25 0 0 114 114 114 37 90 25 0 0 114 114 114 37 90 25 0 0 114 114 114 37 90 25 0 0 114 114 114 37 90 25 0 0 114 114 114 37 91 27 0 0 54 54 21 37 91 27 0 0 54 54 21 37 91 27 0 0 54 54 21 37 91 27 0 0 54 54 21 37 91 27 0 0 54 54 21 37 91 27 0 0 54 54 21 37

165 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

92 28 1 1 37 114 54 54 92 28 1 1 37 114 54 54 92 28 1 1 37 114 54 54 92 28 1 1 37 114 54 54 92 28 1 1 37 114 54 54 92 28 1 1 37 114 54 54 93 26 0 0 54 21 37 37 93 26 0 0 54 21 37 37 93 26 0 0 54 21 37 37 93 26 0 0 54 21 37 37 93 26 0 0 54 21 37 37 93 26 0 0 54 21 37 37 94 25 1 1 54 37 21 0 94 25 1 1 54 37 21 0 94 25 1 1 54 37 21 0 94 25 1 1 54 37 21 0 94 25 1 1 54 37 21 0 94 25 1 1 54 37 21 0 95 25 1 1 37 37 37 0 95 25 1 1 37 37 37 0 95 25 1 1 37 37 37 0 95 25 1 1 37 37 37 0 95 25 1 1 37 37 37 0 95 25 1 1 37 37 37 0 96 38 0 0 37 37 37 37 96 38 0 0 37 37 37 37 96 38 0 0 37 37 37 37 96 38 0 0 37 37 37 37 96 38 0 0 37 37 37 37 96 38 0 0 37 37 37 37 97 25 1 1 37 37 21 21 97 25 1 1 37 37 21 21 97 25 1 1 37 37 21 21 97 25 1 1 37 37 21 21 97 25 1 1 37 37 21 21 97 25 1 1 37 37 21 21 98 18 0 0 54 54 54 21 98 18 0 0 54 54 54 21 98 18 0 0 54 54 54 21 98 18 0 0 54 54 54 21 98 18 0 0 54 54 54 21 98 18 0 0 54 54 54 21

166 SUB AGE SEX SIDE LINS1 LPLC1 LDEP1 LINS2 # yrs 0=female 0=rt VAS VAS VAS VAS 1=male 1=lt SCORE SCORE SCORE SCORE L=LIDO

99 25 0 0 37 37 21 37 99 25 0 0 37 37 21 37 99 25 0 0 37 37 21 37 99 25 0 0 37 37 21 37 99 25 0 0 37 37 21 37 99 25 0 0 37 37 21 37 100 24 0 1 55 62 5 13 100 24 0 1 55 62 5 13 100 24 0 1 55 62 5 13 100 24 0 1 55 62 5 13 100 24 0 1 55 62 5 13 100 24 0 1 55 62 5 13

167 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

1 0 0 38 56 38 38 20 1 1 0 0 38 56 38 38 20 1 1 0 0 38 56 38 38 20 1 1 0 0 38 56 38 38 20 1 1 0 0 38 56 38 38 20 1 1 0 0 38 56 38 38 20 1 2 39 114 84 83 112 54 55 0 2 39 114 84 83 112 54 55 0 2 39 114 84 83 112 54 55 0 2 39 114 84 83 112 54 55 0 2 39 114 84 83 112 54 55 0 2 39 114 84 83 112 54 55 0 3 0 0 37 21 37 0 0 0 3 0 0 37 21 37 0 0 0 3 0 0 37 21 37 0 0 0 3 0 0 37 21 37 0 0 0 3 0 0 37 21 37 0 0 0 3 0 0 37 21 37 0 0 0 4 0 19 21 38 21 0 1 0 4 0 19 21 38 21 0 1 0 4 0 19 21 38 21 0 1 0 4 0 19 21 38 21 0 1 0 4 0 19 21 38 21 0 1 0 4 0 19 21 38 21 0 1 0 5 12 10 42 53 18 31 18 4 5 12 10 42 53 18 31 18 4 5 12 10 42 53 18 31 18 4 5 12 10 42 53 18 31 18 4 5 12 10 42 53 18 31 18 4 5 12 10 42 53 18 31 18 4 6 50 19 70 67 18 74 96 9 6 50 19 70 67 18 74 96 9 6 50 19 70 67 18 74 96 9 6 50 19 70 67 18 74 96 9 6 50 19 70 67 18 74 96 9 6 50 19 70 67 18 74 96 9 7 0 0 21 37 21 0 0 0 7 0 0 21 37 21 0 0 0 7 0 0 21 37 21 0 0 0 7 0 0 21 37 21 0 0 0 7 0 0 21 37 21 0 0 0 7 0 0 21 37 21 0 0 0

168 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

8 0 6 21 54 21 0 21 21 8 0 6 21 54 21 0 21 21 8 0 6 21 54 21 0 21 21 8 0 6 21 54 21 0 21 21 8 0 6 21 54 21 0 21 21 8 0 6 21 54 21 0 21 21 9 21 0 21 37 37 21 21 0 9 21 0 21 37 37 21 21 0 9 21 0 21 37 37 21 21 0 9 21 0 21 37 37 21 21 0 9 21 0 21 37 37 21 21 0 9 21 0 21 37 37 21 21 0 10 5 5 21 108 88 6 34 60 10 5 5 21 108 88 6 34 60 10 5 5 21 108 88 6 34 60 10 5 5 21 108 88 6 34 60 10 5 5 21 108 88 6 34 60 10 5 5 21 108 88 6 34 60 11 21 0 54 54 83 54 37 21 11 21 0 54 54 83 54 37 21 11 21 0 54 54 83 54 37 21 11 21 0 54 54 83 54 37 21 11 21 0 54 54 83 54 37 21 11 21 0 54 54 83 54 37 21 12 0 0 54 54 37 21 37 0 12 0 0 54 54 37 21 37 0 12 0 0 54 54 37 21 37 0 12 0 0 54 54 37 21 37 0 12 0 0 54 54 37 21 37 0 12 0 0 54 54 37 21 37 0 13 37 37 54 54 54 41 42 0 13 37 37 54 54 54 41 42 0 13 37 37 54 54 54 41 42 0 13 37 37 54 54 54 41 42 0 13 37 37 54 54 54 41 42 0 13 37 37 54 54 54 41 42 0 14 23 1 43 52 24 34 26 4 14 23 1 43 52 24 34 26 4 14 23 1 43 52 24 34 26 4 14 23 1 43 52 24 34 26 4 14 23 1 43 52 24 34 26 4 14 23 1 43 52 24 34 26 4

169 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

15 54 0 37 55 21 37 37 21 15 54 0 37 55 21 37 37 21 15 54 0 37 55 21 37 37 21 15 54 0 37 55 21 37 37 21 15 54 0 37 55 21 37 37 21 15 54 0 37 55 21 37 37 21 16 0 0 21 21 37 0 0 0 16 0 0 21 21 37 0 0 0 16 0 0 21 21 37 0 0 0 16 0 0 21 21 37 0 0 0 16 0 0 21 21 37 0 0 0 16 0 0 21 21 37 0 0 0 17 84 55 24 79 71 38 78 80 17 84 55 24 79 71 38 78 80 17 84 55 24 79 71 38 78 80 17 84 55 24 79 71 38 78 80 17 84 55 24 79 71 38 78 80 17 84 55 24 79 71 38 78 80 18 21 21 21 37 2 21 0 0 18 21 21 21 37 2 21 0 0 18 21 21 21 37 2 21 0 0 18 21 21 21 37 2 21 0 0 18 21 21 21 37 2 21 0 0 18 21 21 21 37 2 21 0 0 19 25 21 21 51 34 21 1 0 19 25 21 21 51 34 21 1 0 19 25 21 21 51 34 21 1 0 19 25 21 21 51 34 21 1 0 19 25 21 21 51 34 21 1 0 19 25 21 21 51 34 21 1 0 20 38 24 21 83 21 21 20 21 20 38 24 21 83 21 21 20 21 20 38 24 21 83 21 21 20 21 20 38 24 21 83 21 21 20 21 20 38 24 21 83 21 21 20 21 20 38 24 21 83 21 21 20 21 21 2 21 45 54 42 29 0 0 21 2 21 45 54 42 29 0 0 21 2 21 45 54 42 29 0 0 21 2 21 45 54 42 29 0 0 21 2 21 45 54 42 29 0 0 21 2 21 45 54 42 29 0 0

170 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

22 12 30 47 29 46 12 9 9 22 12 30 47 29 46 12 9 9 22 12 30 47 29 46 12 9 9 22 12 30 47 29 46 12 9 9 22 12 30 47 29 46 12 9 9 22 12 30 47 29 46 12 9 9 23 21 21 37 54 21 37 37 21 23 21 21 37 54 21 37 37 21 23 21 21 37 54 21 37 37 21 23 21 21 37 54 21 37 37 21 23 21 21 37 54 21 37 37 21 23 21 21 37 54 21 37 37 21 24 21 0 37 54 54 0 0 21 24 21 0 37 54 54 0 0 21 24 21 0 37 54 54 0 0 21 24 21 0 37 54 54 0 0 21 24 21 0 37 54 54 0 0 21 24 21 0 37 54 54 0 0 21 25 28 17 86 86 58 57 43 40 25 28 17 86 86 58 57 43 40 25 28 17 86 86 58 57 43 40 25 28 17 86 86 58 57 43 40 25 28 17 86 86 58 57 43 40 25 28 17 86 86 58 57 43 40 26 0 0 15 97 15 0 0 0 26 0 0 15 97 15 0 0 0 26 0 0 15 97 15 0 0 0 26 0 0 15 97 15 0 0 0 26 0 0 15 97 15 0 0 0 26 0 0 15 97 15 0 0 0 27 37 0 54 83 37 21 21 0 27 37 0 54 83 37 21 21 0 27 37 0 54 83 37 21 21 0 27 37 0 54 83 37 21 21 0 27 37 0 54 83 37 21 21 0 27 37 0 54 83 37 21 21 0 28 0 0 21 84 21 0 21 0 28 0 0 21 84 21 0 21 0 28 0 0 21 84 21 0 21 0 28 0 0 21 84 21 0 21 0 28 0 0 21 84 21 0 21 0 28 0 0 21 84 21 0 21 0

171 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

29 54 54 74 74 97 59 59 77 29 54 54 74 74 97 59 59 77 29 54 54 74 74 97 59 59 77 29 54 54 74 74 97 59 59 77 29 54 54 74 74 97 59 59 77 29 54 54 74 74 97 59 59 77 30 30 32 31 30 15 17 17 16 30 30 32 31 30 15 17 17 16 30 30 32 31 30 15 17 17 16 30 30 32 31 30 15 17 17 16 30 30 32 31 30 15 17 17 16 30 30 32 31 30 15 17 17 16 31 60 12 11 57 76 2 2 17 31 60 12 11 57 76 2 2 17 31 60 12 11 57 76 2 2 17 31 60 12 11 57 76 2 2 17 31 60 12 11 57 76 2 2 17 31 60 12 11 57 76 2 2 17 32 0 0 37 37 54 0 0 21 32 0 0 37 37 54 0 0 21 32 0 0 37 37 54 0 0 21 32 0 0 37 37 54 0 0 21 32 0 0 37 37 54 0 0 21 32 0 0 37 37 54 0 0 21 33 0 6 14 22 3 2 13 2 33 0 6 14 22 3 2 13 2 33 0 6 14 22 3 2 13 2 33 0 6 14 22 3 2 13 2 33 0 6 14 22 3 2 13 2 33 0 6 14 22 3 2 13 2 34 37 0 44 83 46 21 54 0 34 37 0 44 83 46 21 54 0 34 37 0 44 83 46 21 54 0 34 37 0 44 83 46 21 54 0 34 37 0 44 83 46 21 54 0 34 37 0 44 83 46 21 54 0 35 4 4 26 47 31 2 1 11 35 4 4 26 47 31 2 1 11 35 4 4 26 47 31 2 1 11 35 4 4 26 47 31 2 1 11 35 4 4 26 47 31 2 1 11 35 4 4 26 47 31 2 1 11

172 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

36 54 21 114 54 37 83 83 37 36 54 21 114 54 37 83 83 37 36 54 21 114 54 37 83 83 37 36 54 21 114 54 37 83 83 37 36 54 21 114 54 37 83 83 37 36 54 21 114 54 37 83 83 37 37 4 9 36 66 80 3 4 22 37 4 9 36 66 80 3 4 22 37 4 9 36 66 80 3 4 22 37 4 9 36 66 80 3 4 22 37 4 9 36 66 80 3 4 22 37 4 9 36 66 80 3 4 22 38 21 0 21 21 37 37 21 0 38 21 0 21 21 37 37 21 0 38 21 0 21 21 37 37 21 0 38 21 0 21 21 37 37 21 0 38 21 0 21 21 37 37 21 0 38 21 0 21 21 37 37 21 0 39 83 54 21 37 37 54 21 0 39 83 54 21 37 37 54 21 0 39 83 54 21 37 37 54 21 0 39 83 54 21 37 37 54 21 0 39 83 54 21 37 37 54 21 0 39 83 54 21 37 37 54 21 0 40 0 0 21 21 21 0 0 0 40 0 0 21 21 21 0 0 0 40 0 0 21 21 21 0 0 0 40 0 0 21 21 21 0 0 0 40 0 0 21 21 21 0 0 0 40 0 0 21 21 21 0 0 0 41 1 0 37 54 54 0 0 1 41 1 0 37 54 54 0 0 1 41 1 0 37 54 54 0 0 1 41 1 0 37 54 54 0 0 1 41 1 0 37 54 54 0 0 1 41 1 0 37 54 54 0 0 1 42 0 0 34 63 41 0 0 0 42 0 0 34 63 41 0 0 0 42 0 0 34 63 41 0 0 0 42 0 0 34 63 41 0 0 0 42 0 0 34 63 41 0 0 0 42 0 0 34 63 41 0 0 0

173 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

43 0 0 21 0 54 0 0 0 43 0 0 21 0 54 0 0 0 43 0 0 21 0 54 0 0 0 43 0 0 21 0 54 0 0 0 43 0 0 21 0 54 0 0 0 43 0 0 21 0 54 0 0 0 44 83 21 54 37 83 21 0 0 44 83 21 54 37 83 21 0 0 44 83 21 54 37 83 21 0 0 44 83 21 54 37 83 21 0 0 44 83 21 54 37 83 21 0 0 44 83 21 54 37 83 21 0 0 45 54 54 54 54 113 0 0 0 45 54 54 54 54 113 0 0 0 45 54 54 54 54 113 0 0 0 45 54 54 54 54 113 0 0 0 45 54 54 54 54 113 0 0 0 45 54 54 54 54 113 0 0 0 46 0 21 37 54 21 21 54 0 46 0 21 37 54 21 21 54 0 46 0 21 37 54 21 21 54 0 46 0 21 37 54 21 21 54 0 46 0 21 37 54 21 21 54 0 46 0 21 37 54 21 21 54 0 47 7 4 21 113 54 8 21 0 47 7 4 21 113 54 8 21 0 47 7 4 21 113 54 8 21 0 47 7 4 21 113 54 8 21 0 47 7 4 21 113 54 8 21 0 47 7 4 21 113 54 8 21 0 48 37 54 21 21 21 0 0 0 48 37 54 21 21 21 0 0 0 48 37 54 21 21 21 0 0 0 48 37 54 21 21 21 0 0 0 48 37 54 21 21 21 0 0 0 48 37 54 21 21 21 0 0 0 49 5 5 54 63 46 28 37 0 49 5 5 54 63 46 28 37 0 49 5 5 54 63 46 28 37 0 49 5 5 54 63 46 28 37 0 49 5 5 54 63 46 28 37 0 49 5 5 54 63 46 28 37 0

174 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

50 117 46 78 110 41 4 3 33 50 117 46 78 110 41 4 3 33 50 117 46 78 110 41 4 3 33 50 117 46 78 110 41 4 3 33 50 117 46 78 110 41 4 3 33 50 117 46 78 110 41 4 3 33 51 54 37 113 83 37 54 83 37 51 54 37 113 83 37 54 83 37 51 54 37 113 83 37 54 83 37 51 54 37 113 83 37 54 83 37 51 54 37 113 83 37 54 83 37 51 54 37 113 83 37 54 83 37 52 0 0 21 21 0 0 0 0 52 0 0 21 21 0 0 0 0 52 0 0 21 21 0 0 0 0 52 0 0 21 21 0 0 0 0 52 0 0 21 21 0 0 0 0 52 0 0 21 21 0 0 0 0 53 41 10 52 51 58 0 0 18 53 41 10 52 51 58 0 0 18 53 41 10 52 51 58 0 0 18 53 41 10 52 51 58 0 0 18 53 41 10 52 51 58 0 0 18 53 41 10 52 51 58 0 0 18 54 59 12 11 121 97 11 128 95 54 59 12 11 121 97 11 128 95 54 59 12 11 121 97 11 128 95 54 59 12 11 121 97 11 128 95 54 59 12 11 121 97 11 128 95 54 59 12 11 121 97 11 128 95 55 21 0 54 113 83 37 21 0 55 21 0 54 113 83 37 21 0 55 21 0 54 113 83 37 21 0 55 21 0 54 113 83 37 21 0 55 21 0 54 113 83 37 21 0 55 21 0 54 113 83 37 21 0 56 21 0 21 54 21 0 0 0 56 21 0 21 54 21 0 0 0 56 21 0 21 54 21 0 0 0 56 21 0 21 54 21 0 0 0 56 21 0 21 54 21 0 0 0 56 21 0 21 54 21 0 0 0

175 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

57 21 3 2 3 19 21 21 21 57 21 3 2 3 19 21 21 21 57 21 3 2 3 19 21 21 21 57 21 3 2 3 19 21 21 21 57 21 3 2 3 19 21 21 21 57 21 3 2 3 19 21 21 21 58 0 0 21 37 83 21 0 0 58 0 0 21 37 83 21 0 0 58 0 0 21 37 83 21 0 0 58 0 0 21 37 83 21 0 0 58 0 0 21 37 83 21 0 0 58 0 0 21 37 83 21 0 0 59 0 0 46 46 46 3 2 2 59 0 0 46 46 46 3 2 2 59 0 0 46 46 46 3 2 2 59 0 0 46 46 46 3 2 2 59 0 0 46 46 46 3 2 2 59 0 0 46 46 46 3 2 2 60 21 6 3 4 4 3 11 3 60 21 6 3 4 4 3 11 3 60 21 6 3 4 4 3 11 3 60 21 6 3 4 4 3 11 3 60 21 6 3 4 4 3 11 3 60 21 6 3 4 4 3 11 3 61 2 2 69 90 17 2 5 4 61 2 2 69 90 17 2 5 4 61 2 2 69 90 17 2 5 4 61 2 2 69 90 17 2 5 4 61 2 2 69 90 17 2 5 4 61 2 2 69 90 17 2 5 4 62 94 48 57 100 18 88 11 13 62 94 48 57 100 18 88 11 13 62 94 48 57 100 18 88 11 13 62 94 48 57 100 18 88 11 13 62 94 48 57 100 18 88 11 13 62 94 48 57 100 18 88 11 13 63 17 18 64 61 34 24 23 34 63 17 18 64 61 34 24 23 34 63 17 18 64 61 34 24 23 34 63 17 18 64 61 34 24 23 34 63 17 18 64 61 34 24 23 34 63 17 18 64 61 34 24 23 34

176 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

64 0 21 37 21 37 0 0 21 64 0 21 37 21 37 0 0 21 64 0 21 37 21 37 0 0 21 64 0 21 37 21 37 0 0 21 64 0 21 37 21 37 0 0 21 64 0 21 37 21 37 0 0 21 65 17 2 59 74 66 3 21 18 65 17 2 59 74 66 3 21 18 65 17 2 59 74 66 3 21 18 65 17 2 59 74 66 3 21 18 65 17 2 59 74 66 3 21 18 65 17 2 59 74 66 3 21 18 66 37 21 54 83 83 21 21 0 66 37 21 54 83 83 21 21 0 66 37 21 54 83 83 21 21 0 66 37 21 54 83 83 21 21 0 66 37 21 54 83 83 21 21 0 66 37 21 54 83 83 21 21 0 67 37 1 54 83 37 21 0 1 67 37 1 54 83 37 21 0 1 67 37 1 54 83 37 21 0 1 67 37 1 54 83 37 21 0 1 67 37 1 54 83 37 21 0 1 67 37 1 54 83 37 21 0 1 68 21 21 37 21 21 21 36 21 68 21 21 37 21 21 21 36 21 68 21 21 37 21 21 21 36 21 68 21 21 37 21 21 21 36 21 68 21 21 37 21 21 21 36 21 68 21 21 37 21 21 21 36 21 69 19 4 26 52 64 27 35 32 69 19 4 26 52 64 27 35 32 69 19 4 26 52 64 27 35 32 69 19 4 26 52 64 27 35 32 69 19 4 26 52 64 27 35 32 69 19 4 26 52 64 27 35 32 70 21 21 21 54 37 0 37 21 70 21 21 21 54 37 0 37 21 70 21 21 21 54 37 0 37 21 70 21 21 21 54 37 0 37 21 70 21 21 21 54 37 0 37 21 70 21 21 21 54 37 0 37 21

177 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

71 83 54 83 83 54 113 83 54 71 83 54 83 83 54 113 83 54 71 83 54 83 83 54 113 83 54 71 83 54 83 83 54 113 83 54 71 83 54 83 83 54 113 83 54 71 83 54 83 83 54 113 83 54 72 56 49 60 37 21 34 26 5 72 56 49 60 37 21 34 26 5 72 56 49 60 37 21 34 26 5 72 56 49 60 37 21 34 26 5 72 56 49 60 37 21 34 26 5 72 56 49 60 37 21 34 26 5 73 37 0 21 37 37 21 0 0 73 37 0 21 37 37 21 0 0 73 37 0 21 37 37 21 0 0 73 37 0 21 37 37 21 0 0 73 37 0 21 37 37 21 0 0 73 37 0 21 37 37 21 0 0 74 54 37 54 54 37 54 37 37 74 54 37 54 54 37 54 37 37 74 54 37 54 54 37 54 37 37 74 54 37 54 54 37 54 37 37 74 54 37 54 54 37 54 37 37 74 54 37 54 54 37 54 37 37 75 83 0 54 0 37 54 0 0 75 83 0 54 0 37 54 0 0 75 83 0 54 0 37 54 0 0 75 83 0 54 0 37 54 0 0 75 83 0 54 0 37 54 0 0 75 83 0 54 0 37 54 0 0 76 0 0 14 21 3 15 1 0 76 0 0 14 21 3 15 1 0 76 0 0 14 21 3 15 1 0 76 0 0 14 21 3 15 1 0 76 0 0 14 21 3 15 1 0 76 0 0 14 21 3 15 1 0 77 7 3 42 74 21 14 2 1 77 7 3 42 74 21 14 2 1 77 7 3 42 74 21 14 2 1 77 7 3 42 74 21 14 2 1 77 7 3 42 74 21 14 2 1 77 7 3 42 74 21 14 2 1

178 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

78 24 39 16 17 18 19 17 23 78 24 39 16 17 18 19 17 23 78 24 39 16 17 18 19 17 23 78 24 39 16 17 18 19 17 23 78 24 39 16 17 18 19 17 23 78 24 39 16 17 18 19 17 23 79 37 34 54 21 54 49 21 21 79 37 34 54 21 54 49 21 21 79 37 34 54 21 54 49 21 21 79 37 34 54 21 54 49 21 21 79 37 34 54 21 54 49 21 21 79 37 34 54 21 54 49 21 21 80 25 13 64 74 40 28 27 7 80 25 13 64 74 40 28 27 7 80 25 13 64 74 40 28 27 7 80 25 13 64 74 40 28 27 7 80 25 13 64 74 40 28 27 7 80 25 13 64 74 40 28 27 7 81 37 21 54 83 37 21 0 0 81 37 21 54 83 37 21 0 0 81 37 21 54 83 37 21 0 0 81 37 21 54 83 37 21 0 0 81 37 21 54 83 37 21 0 0 81 37 21 54 83 37 21 0 0 82 114 21 54 21 0 21 0 0 82 114 21 54 21 0 21 0 0 82 114 21 54 21 0 21 0 0 82 114 21 54 21 0 21 0 0 82 114 21 54 21 0 21 0 0 82 114 21 54 21 0 21 0 0 83 0 0 54 21 83 0 0 0 83 0 0 54 21 83 0 0 0 83 0 0 54 21 83 0 0 0 83 0 0 54 21 83 0 0 0 83 0 0 54 21 83 0 0 0 83 0 0 54 21 83 0 0 0 84 37 21 54 37 21 0 0 0 84 37 21 54 37 21 0 0 0 84 37 21 54 37 21 0 0 0 84 37 21 54 37 21 0 0 0 84 37 21 54 37 21 0 0 0 84 37 21 54 37 21 0 0 0

179 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

85 83 37 83 54 21 83 37 21 85 83 37 83 54 21 83 37 21 85 83 37 83 54 21 83 37 21 85 83 37 83 54 21 83 37 21 85 83 37 83 54 21 83 37 21 85 83 37 83 54 21 83 37 21 86 37 37 37 83 37 21 54 0 86 37 37 37 83 37 21 54 0 86 37 37 37 83 37 21 54 0 86 37 37 37 83 37 21 54 0 86 37 37 37 83 37 21 54 0 86 37 37 37 83 37 21 54 0 87 41 58 80 54 37 70 47 30 87 41 58 80 54 37 70 47 30 87 41 58 80 54 37 70 47 30 87 41 58 80 54 37 70 47 30 87 41 58 80 54 37 70 47 30 87 41 58 80 54 37 70 47 30 88 21 37 37 83 0 54 37 0 88 21 37 37 83 0 54 37 0 88 21 37 37 83 0 54 37 0 88 21 37 37 83 0 54 37 0 88 21 37 37 83 0 54 37 0 88 21 37 37 83 0 54 37 0 89 22 0 21 37 21 21 21 0 89 22 0 21 37 21 21 21 0 89 22 0 21 37 21 21 21 0 89 22 0 21 37 21 21 21 0 89 22 0 21 37 21 21 21 0 89 22 0 21 37 21 21 21 0 90 21 21 143 143 114 83 54 21 90 21 21 143 143 114 83 54 21 90 21 21 143 143 114 83 54 21 90 21 21 143 143 114 83 54 21 90 21 21 143 143 114 83 54 21 90 21 21 143 143 114 83 54 21 91 37 21 37 83 21 21 37 21 91 37 21 37 83 21 21 37 21 91 37 21 37 83 21 21 37 21 91 37 21 37 83 21 21 37 21 91 37 21 37 83 21 21 37 21 91 37 21 37 83 21 21 37 21

180 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

92 21 21 37 114 83 0 0 0 92 21 21 37 114 83 0 0 0 92 21 21 37 114 83 0 0 0 92 21 21 37 114 83 0 0 0 92 21 21 37 114 83 0 0 0 92 21 21 37 114 83 0 0 0 93 21 14 54 37 21 54 0 0 93 21 14 54 37 21 54 0 0 93 21 14 54 37 21 54 0 0 93 21 14 54 37 21 54 0 0 93 21 14 54 37 21 54 0 0 93 21 14 54 37 21 54 0 0 94 45 21 54 54 37 0 37 21 94 45 21 54 54 37 0 37 21 94 45 21 54 54 37 0 37 21 94 45 21 54 54 37 0 37 21 94 45 21 54 54 37 0 37 21 94 45 21 54 54 37 0 37 21 95 0 21 37 54 21 37 0 0 95 0 21 37 54 21 37 0 0 95 0 21 37 54 21 37 0 0 95 0 21 37 54 21 37 0 0 95 0 21 37 54 21 37 0 0 95 0 21 37 54 21 37 0 0 96 37 0 37 37 21 21 21 0 96 37 0 37 37 21 21 21 0 96 37 0 37 37 21 21 21 0 96 37 0 37 37 21 21 21 0 96 37 0 37 37 21 21 21 0 96 37 0 37 37 21 21 21 0 97 54 21 21 21 21 21 21 0 97 54 21 21 21 21 21 21 0 97 54 21 21 21 21 21 21 0 97 54 21 21 21 21 21 21 0 97 54 21 21 21 21 21 21 0 97 54 21 21 21 21 21 21 0 98 21 21 53 52 83 23 21 2 98 21 21 53 52 83 23 21 2 98 21 21 53 52 83 23 21 2 98 21 21 53 52 83 23 21 2 98 21 21 53 52 83 23 21 2 98 21 21 53 52 83 23 21 2

181 SUB LPLC2 LDEP2 CINS1 CPLC1 CDEP1 CINS2 CPLC2 CDEP2 # VAS VAS VAS VAS VAS VAS VAS VAS SCORE SCORE SCORE SCORE SCORE SCORE SCORE SCORE C=COMBO

99 21 0 54 54 83 37 21 21 99 21 0 54 54 83 37 21 21 99 21 0 54 54 83 37 21 21 99 21 0 54 54 83 37 21 21 99 21 0 54 54 83 37 21 21 99 21 0 54 54 83 37 21 21 100 0 0 54 90 21 64 21 2 100 0 0 54 90 21 64 21 2 100 0 0 54 90 21 64 21 2 100 0 0 54 90 21 64 21 2 100 0 0 54 90 21 64 21 2 100 0 0 54 90 21 64 21 2

182 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 1 1 9 29 0 0 0 0 0 0 1 2 . . 0 0 . . . . 1 3 . 25 0 0 . 1 . 1 1 4 . 21 0 0 . 1 . 0 1 5 . 25 0 0 . 1 . 0 1 6 . . 0 0 . . . . 2 1 . 9 0 0 . 0 . 1 2 2 53 13 0 0 0 0 0 1 2 3 45 13 0 1 1 0 1 0 2 4 . 13 0 0 . 0 . 1 2 5 . 9 0 0 . 0 . 1 2 6 . . 0 0 . . . . 3 1 5 29 0 0 0 1 1 1 3 2 5 41 0 0 0 1 1 0 3 3 . . 0 0 . . . . 3 4 . . 0 0 . . . . 3 5 . . 0 0 . . . . 3 6 . . 0 0 . . . . 4 1 5 5 1 1 0 0 0 0 4 2 5 5 1 1 0 0 0 0 4 3 25 5 0 1 1 0 0 0 4 4 5 5 1 1 0 0 0 0 4 5 17 5 0 1 0 0 1 0 4 6 . . 0 0 . . . . 5 1 9 . 0 0 0 . 1 . 5 2 9 9 1 1 0 0 1 0 5 3 ...... 5 4 17 9 1 1 0 0 0 0 5 5 9 5 1 1 0 0 0 0 5 6 . 9 0 0 . 0 . 1 6 1 5 5 1 1 0 0 0 0 6 2 5 9 1 1 0 0 0 0 6 3 5 9 1 1 0 0 0 0 6 4 5 9 1 1 0 0 0 0 6 5 5 9 1 1 0 0 1 0 6 6 . . 0 0 . . . . 7 1 21 5 0 0 0 0 1 0 7 2 . . 0 0 . . . . 7 3 . . 0 0 . . . . 7 4 . . 0 0 . . . . 7 5 . . 0 0 . . . . 7 6 . . 0 0 . . . .

183 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 8 1 9 21 1 0 0 1 0 0 8 2 9 29 1 0 0 1 0 0 8 3 9 29 1 0 0 1 0 0 8 4 9 25 1 0 0 1 0 0 8 5 . . 0 0 . . . . 8 6 . . 0 0 . . . . 9 1 9 13 1 0 . 0 . 1 9 2 9 5 1 1 . . . . 9 3 . . 0 0 0 0 0 0 9 4 9 5 1 1 . . . . 9 5 . . 0 0 0 0 0 0 9 6 . . 0 0 0 0 0 0 10 1 53 . 0 0 0 . 0 . 10 2 53 . 0 0 1 . 0 . 10 3 17 . 1 0 0 . 0 . 10 4 17 . 0 0 0 . 1 . 10 5 . . 0 0 . . . . 10 6 . . 0 0 . . . . 11 1 9 5 1 1 0 0 0 0 11 2 . 25 0 0 . 1 . 0 11 3 9 5 1 1 0 0 0 0 11 4 9 5 1 1 0 0 0 0 11 5 13 9 1 1 0 0 0 0 11 6 13 13 1 0 0 0 0 1 12 1 9 5 0 1 0 0 1 0 12 2 5 5 0 1 0 0 1 0 12 3 9 5 1 1 0 0 0 0 12 4 9 9 1 1 0 0 0 0 12 5 . . 0 0 . . . . 12 6 . . 0 0 . . . . 13 1 9 29 1 0 0 1 0 0 13 2 13 . 1 0 0 . 0 . 13 3 25 . 0 0 1 . 0 . 13 4 21 . 0 0 1 . 0 . 13 5 13 49 1 0 0 1 0 0 13 6 33 . 0 0 1 . 1 . 14 1 . 13 0 0 . 0 . 1 14 2 21 13 0 0 0 0 0 1 14 3 5 5 1 1 0 0 0 0 14 4 ...... 14 5 . . 0 0 . . . . 14 6 . 5 0 0 . 0 . 0

184 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 15 1 5 5 1 1 0 0 0 0 15 2 9 13 0 0 0 0 1 1 15 3 13 17 0 0 0 0 1 0 15 4 13 13 1 1 0 0 0 0 15 5 . . 0 0 . . . . 15 6 . . 0 0 . . . . 16 1 13 5 1 1 0 0 0 0 16 2 17 13 1 1 0 0 0 0 16 3 21 9 0 1 1 0 0 0 16 4 21 17 0 1 1 0 0 0 16 5 29 13 0 1 1 0 1 0 16 6 . . 0 0 . . . . 17 1 13 21 1 0 0 1 0 0 17 2 13 . 1 0 0 . 0 . 17 3 13 . 1 0 0 . 0 . 17 4 25 . 0 0 1 . 0 . 17 5 . . 0 0 . . . . 17 6 . . 0 0 . . . . 18 1 . 5 0 0 . 0 . 1 18 2 . 49 0 0 . 1 . 0 18 3 . . 0 0 . . . . 18 4 . 5 0 0 . 0 . 1 18 5 . . 0 0 . . . . 18 6 . . 0 0 . . . . 19 1 9 33 1 0 0 0 0 1 19 2 . . 0 0 . . . . 19 3 . . 0 0 . . . . 19 4 . 37 0 0 . 1 . 0 19 5 . 53 0 0 . 1 . 0 19 6 . . 0 0 . . . . 20 1 9 5 1 1 0 0 0 0 20 2 5 5 1 1 0 0 0 0 20 3 5 5 1 1 0 0 0 0 20 4 9 5 1 1 0 0 0 0 20 5 9 13 0 1 0 0 1 0 20 6 . . 0 0 . . . . 21 1 33 . 0 0 0 . 0 . 21 2 . . 0 0 . . . . 21 3 9 13 1 1 0 0 0 0 21 4 ...... 21 5 21 13 1 1 1 0 0 0 21 6 5 5 1 1 0 0 0 0

185 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 22 1 5 21 1 0 0 1 0 0 22 2 5 . 1 0 0 . 0 . 22 3 21 29 0 0 1 1 1 1 22 4 . . 0 0 . . . . 22 5 . . 0 0 . . . . 22 6 . . 0 0 . . . . 23 1 17 5 1 1 0 0 0 0 23 2 17 13 0 0 0 0 1 0 23 3 29 21 0 0 1 1 0 1 23 4 17 13 0 0 0 0 1 1 23 5 . . 0 0 . . . . 23 6 . . 0 0 . . . . 24 1 . . 0 0 . . . . 24 2 37 . 0 0 1 . 1 . 24 3 . . 0 0 . . . . 24 4 13 21 0 1 0 0 1 0 24 5 13 13 1 1 0 0 0 0 24 6 . . 0 0 . . . . 25 1 9 5 1 1 0 0 0 0 25 2 13 5 1 1 0 0 0 0 25 3 17 5 1 1 0 0 0 0 25 4 17 5 1 0 0 0 0 1 25 5 . . 0 0 . . . . 25 6 17 21 0 0 0 1 1 1 26 1 . 13 0 0 . 0 . 1 26 2 . 9 0 1 . 0 . 0 26 3 . 9 0 1 . 0 . 0 26 4 . 9 0 1 . 0 . 0 26 5 . 9 0 1 . 0 . 0 26 6 . 9 0 1 . 0 . 0 27 1 9 45 0 0 0 1 1 0 27 2 53 . 0 0 1 . 0 . 27 3 37 . 0 0 1 . 0 . 27 4 13 21 1 1 0 1 0 0 27 5 21 21 1 1 1 1 0 0 27 6 . . 0 0 . . . . 28 1 5 9 1 1 0 0 0 0 28 2 5 9 1 1 0 0 0 0 28 3 5 9 1 1 0 0 0 0 28 4 5 9 0 1 0 0 1 0 28 5 29 9 0 0 1 0 1 1 28 6 . . 0 0 . . . .

186 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 29 1 5 9 0 1 0 0 1 0 29 2 . . 0 0 . . . . 29 3 5 13 1 1 0 0 0 0 29 4 5 13 1 0 0 0 0 1 29 5 13 13 1 1 0 0 0 0 29 6 . 5 0 0 . 0 . 1 30 1 . 5 0 1 . 0 . 0 30 2 5 9 1 1 0 0 0 0 30 3 ...... 30 4 13 21 1 1 0 1 0 0 30 5 . . 0 0 . . . . 30 6 . . 0 0 . . . . 31 1 . . 0 0 . . . . 31 2 . . 0 0 . . . . 31 3 . . 0 0 . . . . 31 4 17 33 0 0 0 1 1 0 31 5 . . 0 0 . . . . 31 6 . . 0 0 . . . . 32 1 5 21 1 0 0 1 0 1 32 2 13 . 0 0 0 . 1 . 32 3 5 . 1 0 0 . 0 . 32 4 9 . 1 0 0 . 0 . 32 5 25 . 0 0 1 . 1 . 32 6 . . 0 0 . . . . 33 1 21 5 0 1 1 0 1 0 33 2 . 9 0 1 . 0 . 0 33 3 . 5 0 1 . 0 . 0 33 4 . 9 0 1 . 0 . 0 33 5 . 9 0 1 . 0 . 0 33 6 . . 0 0 . . . . 34 1 . 5 0 1 . 0 . 0 34 2 . 5 0 1 . 0 . 0 34 3 21 5 0 1 1 0 1 0 34 4 . 33 0 0 . 1 . 0 34 5 . . 0 0 . . . . 34 6 . . 0 0 . . . . 35 1 . . 0 0 . . . . 35 2 . . 0 0 . . . . 35 3 . . 0 0 . . . . 35 4 . . 0 0 . . . . 35 5 . . 0 0 . . . . 35 6 . . 0 0 . . . .

187 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 36 1 13 45 1 0 0 1 0 0 36 2 . . 0 0 . . . . 36 3 21 . 0 0 0 . 1 . 36 4 17 53 1 0 0 1 0 0 36 5 33 . 0 0 1 . 1 . 36 6 53 . 0 0 1 . 0 . 37 1 . 29 0 0 . 1 . 0 37 2 . 53 0 0 . 1 . 0 37 3 . 29 0 0 . 1 . 0 37 4 . 21 0 1 . 1 . 0 37 5 . 17 0 0 . 0 . 1 37 6 . . 0 0 . . . . 38 1 45 . 0 0 1 . 1 . 38 2 . . 0 0 . . . . 38 3 . . 0 0 . . . . 38 4 . . 0 0 . . . . 38 5 . . 0 0 . . . . 38 6 . . 0 0 . . . . 39 1 5 21 1 1 0 1 0 0 39 2 37 . 0 0 1 . 0 . 39 3 17 . 0 0 0 . 1 . 39 4 13 49 0 0 0 1 1 0 39 5 . . 0 0 . . . . 39 6 . . 0 0 . . . . 40 1 ...... 40 2 33 13 0 1 1 0 0 0 40 3 37 13 0 1 1 0 0 0 40 4 37 17 0 1 1 0 0 0 40 5 41 21 0 1 1 1 0 0 40 6 . . 0 0 . . . . 41 1 25 9 0 0 1 0 0 1 41 2 13 9 1 1 0 0 0 0 41 3 13 13 0 0 0 0 1 1 41 4 9 9 1 0 0 0 0 1 41 5 . . 0 0 . . . . 41 6 . . 0 0 . . . . 42 1 5 9 1 1 0 0 0 0 42 2 9 13 0 1 0 0 1 0 42 3 5 9 1 1 0 0 0 0 42 4 5 9 1 1 0 0 0 0 42 5 13 9 0 0 0 0 1 1 42 6 . 29 0 . .

188 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 43 1 5 9 0 0 0 0 0 0 43 2 5 17 0 0 0 0 1 0 43 3 . 21 0 0 . 1 . 0 43 4 29 21 0 0 1 1 0 1 43 5 . 21 0 0 . 1 . 0 43 6 . 21 0 0 . 1 . 1 44 1 5 5 1 1 0 0 0 0 44 2 9 5 1 1 0 0 0 0 44 3 9 5 1 1 0 0 0 0 44 4 13 9 1 1 0 0 0 0 44 5 21 9 1 1 1 0 0 0 44 6 29 5 0 1 1 0 0 0 45 1 25 . 0 0 1 . 0 . 45 2 . . 0 0 . . . . 45 3 29 . 0 0 1 . 0 . 45 4 . . 0 0 . . . . 45 5 . . 0 0 . . . . 45 6 . . 0 0 . . . . 46 1 5 13 1 0 0 0 0 1 46 2 5 9 1 0 0 0 0 1 46 3 . . 0 0 . . . . 46 4 9 5 1 0 0 0 0 1 46 5 . . 0 0 . . . . 46 6 . . 0 0 . . . . 47 1 13 5 1 1 0 0 0 0 47 2 17 9 1 1 0 0 0 0 47 3 13 9 1 1 0 0 0 0 47 4 13 9 0 1 0 0 1 0 47 5 . . 0 0 . . . . 47 6 . . 0 0 . . . . 48 1 13 13 0 1 0 0 0 0 48 2 . 13 0 1 . 0 . 0 48 3 . 17 0 0 . 0 . 0 48 4 . 17 0 1 . 0 . 0 48 5 . . 0 0 . . . . 48 6 . . 0 0 . . . . 49 1 17 5 1 1 0 0 0 0 49 2 9 5 1 1 0 0 0 0 49 3 9 5 1 1 0 0 0 0 49 4 9 9 1 1 0 0 0 0 49 5 13 9 1 1 0 0 0 0 49 6 21 9 1 1 1 0 0 0

189 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 50 1 5 5 1 1 0 0 0 0 50 2 5 9 1 1 0 0 0 0 50 3 5 5 1 1 0 0 0 0 50 4 5 9 1 1 0 0 0 0 50 5 5 17 1 1 0 0 0 0 50 6 13 17 1 1 0 0 0 0 51 1 5 13 0 1 0 0 1 0 51 2 5 5 0 0 0 0 0 1 51 3 . . 0 0 . . . . 51 4 49 5 0 0 1 0 0 1 51 5 . . 0 0 . . . . 51 6 . . 0 0 . . . . 52 1 5 13 1 1 0 0 0 0 52 2 9 17 1 1 0 0 0 0 52 3 9 17 1 1 0 0 0 0 52 4 9 53 1 0 0 1 0 0 52 5 33 . 0 0 1 . 0 . 52 6 . . 0 0 . . . . 53 1 5 5 1 1 0 0 0 0 53 2 5 9 1 1 0 0 0 0 53 3 5 9 1 1 0 0 0 0 53 4 5 5 1 1 0 0 0 0 53 5 5 9 1 1 0 0 0 0 53 6 5 9 1 1 0 0 0 0 54 1 5 5 1 0 0 0 0 1 54 2 5 29 1 0 0 1 0 0 54 3 ...... 54 4 5 13 1 1 0 0 0 0 54 5 . . 0 0 . . . . 54 6 . . 0 0 . . . . 55 1 13 5 1 1 0 0 0 0 55 2 13 . 0 0 0 . 1 . 55 3 13 9 1 1 0 0 0 0 55 4 ...... 55 5 13 21 1 0 0 1 0 1 55 6 21 25 1 0 1 1 0 1 56 1 9 5 1 1 0 0 0 0 56 2 17 5 1 1 0 0 0 0 56 3 5 9 0 1 0 0 1 0 56 4 5 9 1 1 0 0 0 0 56 5 53 . 0 0 1 . 0 . 56 6 . . 0 0 . . . .

190 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 57 1 5 9 1 1 0 0 0 0 57 2 37 . 0 0 1 . 0 . 57 3 41 13 0 0 1 0 0 1 57 4 17 13 0 1 0 0 1 0 57 5 33 . 0 0 1 . 1 . 57 6 . . 0 0 . . . . 58 1 17 13 1 0 0 0 0 0 58 2 49 33 0 0 1 1 0 1 58 3 33 25 0 0 1 1 1 0 58 4 25 21 0 0 1 1 0 1 58 5 . . 0 0 . . . . 58 6 . . 0 0 . . . . 59 1 5 5 1 1 0 0 0 0 59 2 5 17 1 1 0 0 0 0 59 3 5 17 1 1 0 0 0 0 59 4 5 17 1 1 0 0 0 0 59 5 5 13 1 1 0 0 0 0 59 6 . . 0 0 . . . . 60 1 9 5 1 0 0 0 0 1 60 2 . 41 0 0 . 1 . 0 60 3 21 9 1 0 1 0 0 1 60 4 17 9 1 1 0 0 0 0 60 5 13 9 1 0 0 0 0 1 60 6 9 49 0 0 0 1 1 0 61 1 5 13 1 1 0 0 0 0 61 2 9 17 1 0 0 0 0 1 61 3 13 17 1 0 0 0 0 1 61 4 13 17 1 1 0 0 0 0 61 5 . . 0 0 . . . . 61 6 . . 0 0 . . . . 62 1 9 5 0 1 0 0 1 0 62 2 5 5 1 1 0 0 0 0 62 3 5 13 0 1 0 0 1 0 62 4 5 9 1 1 0 0 0 0 62 5 5 9 1 1 0 0 0 0 62 6 5 13 1 0 0 0 0 1 63 1 37 5 0 1 1 0 1 0 63 2 . 9 0 1 . 0 . 0 63 3 . 9 0 0 . 0 . 1 63 4 . 13 0 1 . 0 . 0 63 5 . . 0 0 . . . . 63 6 . . 0 0 . . . .

191 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 64 1 9 5 0 1 0 0 1 0 64 2 5 9 0 1 0 0 1 0 64 3 . 41 0 0 . 1 . 0 64 4 13 9 0 1 0 0 1 0 64 5 13 17 0 1 0 0 1 0 64 6 . 13 0 0 . 0 . 1 65 1 25 . 0 0 1 . 0 . 65 2 5 5 1 1 0 0 0 0 65 3 13 5 0 0 0 0 1 1 65 4 13 9 1 0 0 0 0 1 65 5 17 9 1 1 0 0 0 0 65 6 13 49 1 0 0 1 0 0 66 1 5 5 1 1 0 0 0 0 66 2 9 5 1 1 0 0 0 0 66 3 17 5 1 1 0 0 0 0 66 4 13 5 1 1 0 0 0 0 66 5 17 9 1 1 0 0 0 0 66 6 17 13 0 1 0 0 1 0 67 1 13 17 1 1 0 0 0 0 67 2 17 17 0 1 0 0 1 0 67 3 21 17 1 1 1 0 0 0 67 4 21 17 1 1 1 0 0 0 67 5 . . 0 0 . . . . 67 6 37 41 0 0 1 1 0 0 68 1 5 5 1 1 0 0 0 0 68 2 . 5 0 1 . 0 . 0 68 3 . 5 0 0 . 0 . 1 68 4 5 5 0 0 0 0 1 1 68 5 . . 0 0 . . . . 68 6 . . 0 0 . . . . 69 1 5 5 1 1 0 0 0 0 69 2 9 13 1 1 0 0 0 0 69 3 5 13 1 1 0 0 0 0 69 4 9 17 1 1 0 0 0 0 69 5 . 17 0 0 . 0 . 0 69 6 . . 0 0 . . . . 70 1 13 . 0 0 1 . 1 . 70 2 . 21 0 0 . 1 . 1 70 3 . 45 0 0 . 1 . 0 70 4 . 9 0 0 . 0 . 1 70 5 . 13 0 1 . 0 . 0 70 6 . . 0 0 . . . .

192 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 71 1 5 17 1 0 0 0 0 1 71 2 13 5 1 0 0 0 0 1 71 3 5 5 1 1 0 0 0 0 71 4 13 17 1 1 0 0 0 0 71 5 53 . 0 0 1 . 0 . 71 6 . . 0 0 . . . . 72 1 9 17 1 1 0 0 0 0 72 2 17 25 0 0 0 1 1 0 72 3 45 29 0 0 1 1 0 0 72 4 9 9 0 0 0 0 1 1 72 5 41 33 0 0 1 1 0 0 72 6 . 41 0 0 . 1 . 0 73 1 5 9 1 0 0 0 0 0 73 2 9 5 1 1 0 0 0 0 73 3 17 33 0 0 0 1 1 0 73 4 13 9 0 0 0 0 1 1 73 5 . . 0 0 . . . . 73 6 . . 0 0 . . . . 74 1 9 5 1 1 0 0 0 0 74 2 13 9 1 1 0 0 0 0 74 3 21 9 1 1 1 0 0 0 74 4 13 9 1 1 0 0 0 0 74 5 13 9 1 1 0 0 0 0 74 6 25 17 0 1 1 0 0 0 75 1 5 13 1 0 0 0 0 1 75 2 29 . 0 0 1 . 1 . 75 3 5 5 1 0 0 0 0 1 75 4 5 5 1 0 0 0 0 1 75 5 5 5 0 0 0 0 1 1 75 6 5 17 1 0 0 0 0 1 76 1 41 9 0 0 1 0 0 1 76 2 9 . 0 0 0 . 1 . 76 3 . . 0 0 . . . . 76 4 21 . 1 0 1 . 0 . 76 5 . . 0 0 . . . . 76 6 . . 0 0 . . . . 77 1 13 . 1 0 0 . 0 . 77 2 37 . 0 0 1 . 1 . 77 3 17 . 1 0 0 . 0 . 77 4 21 . 1 0 1 . 0 . 77 5 17 53 1 0 0 1 0 0 77 6 37 . 0 0 1 . 0 .

193 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 78 1 5 5 1 1 0 0 0 0 78 2 9 5 1 1 0 0 0 0 78 3 9 5 1 1 0 0 0 0 78 4 13 13 1 1 0 0 0 0 78 5 17 29 0 0 0 1 1 1 78 6 . 37 0 0 . 1 . 1 79 1 5 5 1 1 0 0 0 0 79 2 9 9 1 1 0 0 0 0 79 3 9 9 1 1 0 0 0 0 79 4 9 9 1 1 0 0 0 0 79 5 21 9 1 1 1 0 0 0 79 6 25 9 0 1 1 0 0 0 80 1 5 5 0 1 0 0 1 0 80 2 5 5 1 0 0 0 0 1 80 3 5 5 0 1 0 0 1 0 80 4 5 5 1 1 0 0 0 0 80 5 53 13 0 1 1 0 0 0 80 6 13 45 0 0 0 1 1 0 81 1 13 9 0 1 0 0 0 0 81 2 . 13 0 0 . 0 . 0 81 3 . . 0 0 . . . . 81 4 17 9 0 1 0 0 1 0 81 5 . . 0 0 . . . . 81 6 . . 0 0 . . . . 82 1 5 13 1 1 0 0 0 0 82 2 21 21 0 1 1 1 1 0 82 3 5 17 0 1 0 0 1 0 82 4 29 17 0 1 1 0 0 0 82 5 9 17 1 0 0 0 0 0 82 6 37 . 0 0 1 . 1 . 83 1 21 5 1 1 1 0 0 0 83 2 29 29 0 0 1 1 1 1 83 3 13 13 1 1 0 0 0 0 83 4 17 17 1 0 0 0 0 1 83 5 49 . 0 0 1 . 0 . 83 6 . . 0 0 . . . . 84 1 5 25 1 0 0 1 0 1 84 2 5 21 0 0 0 0 0 0 84 3 5 9 0 0 0 0 0 0 84 4 5 9 0 0 0 0 0 0 84 5 5 . 0 0 0 . 0 . 84 6 . . 0 0 . . . .

194 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 85 1 9 5 1 1 0 0 0 0 85 2 9 9 1 1 0 0 0 0 85 3 ...... 85 4 13 9 1 0 0 0 0 0 85 5 . . 0 0 . . . . 85 6 . . 0 0 . . . . 86 1 9 13 0 1 0 0 0 0 86 2 25 13 0 1 1 0 0 0 86 3 . 29 0 1 . 0 . 0 86 4 25 17 0 1 1 0 0 0 86 5 . . 0 0 . . . . 86 6 21 17 1 1 1 0 0 0 87 1 5 5 1 0 0 0 0 1 87 2 . . 0 0 . . . . 87 3 . 9 0 1 . 0 . 0 87 4 . 49 0 0 . 1 . 0 87 5 . 45 0 0 . 1 . 0 87 6 . . 0 0 . . . . 88 1 5 . 0 0 0 . 1 . 88 2 5 5 0 0 0 0 1 1 88 3 5 5 0 0 0 0 1 1 88 4 5 5 0 0 0 0 1 1 88 5 . . 0 0 . . . . 88 6 . . 0 0 . . . . 89 1 25 5 0 0 1 0 0 1 89 2 33 . 0 0 1 . 0 . 89 3 29 25 0 0 1 1 0 1 89 4 39 49 0 0 1 1 0 0 89 5 . . 0 0 . . . . 89 6 . . 0 0 . . . . 90 1 5 9 1 1 0 0 0 0 90 2 . . 0 0 . . . . 90 3 13 9 1 0 0 0 0 1 90 4 13 9 1 1 0 0 0 0 90 5 13 9 1 0 0 0 0 1 90 6 13 9 0 0 0 0 1 1 91 1 25 13 0 0 1 0 0 1 91 2 . . 0 0 . . . . 91 3 29 17 0 0 1 0 1 1 91 4 . . 0 0 . . . . 91 5 . . 0 0 . . . . 91 6 . . 0 0 . . . .

195 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 92 1 5 5 1 1 0 0 0 0 92 2 5 9 1 1 0 0 0 0 92 3 41 13 0 1 1 0 0 0 92 4 13 13 0 1 0 0 1 0 92 5 21 13 1 1 1 0 0 0 92 6 17 . 0 0 0 . 1 . 93 1 45 5 0 0 1 0 0 1 93 2 17 9 1 1 0 0 0 0 93 3 13 5 1 1 0 0 0 0 93 4 17 5 1 1 0 0 0 0 93 5 17 5 1 1 0 0 0 0 93 6 . . 0 0 . . . . 94 1 . 17 0 0 . 0 . 1 94 2 . 17 0 1 . 0 . 0 94 3 . 53 0 0 . 1 . 0 94 4 . 25 0 0 . 1 . 0 94 5 . . 0 0 . . . . 94 6 . . 0 0 . . . . 95 1 . . 0 0 . . . . 95 2 . . 0 0 . . . . 95 3 25 21 0 0 1 1 1 1 95 4 25 21 0 1 1 1 1 0 95 5 . . 0 0 . . . . 95 6 . . 0 0 . . . . 96 1 5 17 0 0 0 0 1 1 96 2 5 . 0 0 0 . 1 . 96 3 ...... 96 4 5 9 1 1 0 0 0 0 96 5 . . 0 0 . . . . 96 6 . . 0 0 . . . . 97 1 5 5 1 0 0 0 0 1 97 2 13 . 1 0 0 . 0 . 97 3 13 29 1 0 0 1 0 1 97 4 13 45 1 0 0 1 0 0 97 5 5 5 1 1 0 0 0 0 97 6 45 . 0 0 1 . 0 . 98 1 5 5 0 1 0 0 1 0 98 2 . 33 0 0 . 1 . 0 98 3 ...... 98 4 17 17 0 1 0 0 1 0 98 5 . . 0 0 . . . . 98 6 . . 0 0 . . . .

196 SUB TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT # 1=2MOL 2 2 consecutive any 0 after 2 2=1MOL time of the first consecutive 80 readings consecutive 80s, 3=2PRE of two consecutive 80 readings after followed by 4=1PRE 80 readings within 15 minutes another 80 5=LATINC *with the exception of success, data is only record 6=CENTINC 99 1 5 9 1 1 0 0 0 0 99 2 5 25 0 0 0 1 1 1 99 3 5 13 0 0 0 0 1 1 99 4 . 41 0 0 . 1 . 1 99 5 . . 0 0 . . . . 99 6 . . 0 0 . . . . 100 1 5 9 1 1 0 0 0 0 100 2 5 5 1 1 0 0 0 0 100 3 9 5 1 1 0 0 0 0 100 4 9 5 1 1 0 0 0 0 100 5 9 5 1 1 0 0 0 0 100 6 . . 0 0 . . . .

197 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

1 1 1 4 8 0 1 1 0 0 0 0 0 1 . . . . 0 0 0 0 0 0 0 0 1 . 1 . 20 0 0 0 0 0 0 0 0 1 . 1 . 8 0 0 0 0 0 0 0 0 1 . 1 . 12 0 0 0 0 0 0 0 0 1 . . . . 0 0 0 0 0 0 0 0 2 . 0 . 48 0 1 0 0 1 0 0 0 2 0 0 4 44 0 1 0 0 0 0 0 0 2 0 0 12 44 0 0 0 0 0 0 0 1 2 . 0 . 44 0 0 0 0 0 0 0 0 2 . 1 . 40 0 0 0 0 0 0 0 0 2 . . . . 0 0 0 0 0 0 0 0 3 1 0 52 28 1 1 1 1 0 0 1 0 3 1 1 33 4 1 1 0 0 0 0 0 1 3 . . . . 0 0 0 0 0 0 0 0 3 . . . . 0 0 0 0 0 0 0 0 3 . . . . 0 0 0 0 0 0 0 0 3 . . . . 0 0 0 0 0 0 0 0 4 0 0 52 52 1 1 1 1 1 1 1 1 4 0 0 52 52 1 1 1 1 1 1 1 1 4 0 0 32 52 0 0 0 0 0 1 1 1 4 0 0 52 52 1 1 1 1 1 1 1 1 4 0 0 40 52 1 0 0 1 1 0 1 0 4 . . . . 0 0 0 0 0 0 0 0 5 1 . 44 . 0 1 1 1 1 1 0 0 5 0 0 48 48 0 1 1 1 1 1 1 1 5 ...... 5 0 0 40 48 0 0 0 1 1 1 1 1 5 0 0 48 52 0 1 1 1 1 1 1 1 5 . 1 . 36 0 0 0 0 0 0 0 0 6 0 0 52 52 1 1 1 1 1 1 1 1 6 0 0 52 48 1 1 1 1 1 1 1 1 6 0 0 52 48 1 1 1 1 1 1 1 1 6 0 0 52 48 1 1 1 1 1 1 1 1 6 0 0 52 48 1 1 1 1 1 1 0 1 6 . . . . 0 0 0 0 0 0 0 0 7 1 1 28 4 1 0 0 0 1 1 0 0 7 . . . . 0 0 0 0 0 0 0 0 7 . . . . 0 0 0 0 0 0 0 0 7 . . . . 0 0 0 0 0 0 0 0 7 . . . . 0 0 0 0 0 0 0 0 7 . . . . 0 0 0 0 0 0 0 0

198 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

8 0 0 48 36 0 1 1 1 1 1 1 1 8 0 0 48 28 0 1 1 1 1 1 1 1 8 0 0 48 28 0 1 1 1 1 1 1 1 8 0 0 48 32 0 1 1 1 1 1 1 1 8 . . . . 0 0 0 0 0 0 0 0 8 . . . . 0 0 0 0 0 0 0 0 9 . 1 48 32 0 1 1 1 1 1 1 1 9 . . 48 52 0 1 1 1 1 1 1 1 9 0 0 . . 0 0 0 0 0 0 0 0 9 . . 48 52 0 1 1 1 1 1 1 1 9 0 0 . . 0 0 0 0 0 0 0 0 9 0 0 . . 0 0 0 0 0 0 0 0 10 0 . 4 . 0 0 1 0 0 0 0 1 10 0 . 4 . 0 0 0 0 0 0 0 0 10 0 . 40 . 0 0 0 1 1 1 1 1 10 0 . 40 . 0 0 0 1 1 1 0 1 10 . . . . 0 0 0 0 0 0 0 0 10 . . . . 0 0 0 0 0 0 0 0 11 0 0 48 52 0 1 1 1 1 1 1 1 11 . 1 . 8 0 0 0 0 0 0 0 0 11 0 0 48 52 0 1 1 1 1 1 1 1 11 0 0 48 52 0 1 1 1 1 1 1 1 11 0 0 44 48 0 0 1 1 1 1 1 1 11 0 0 44 44 0 0 1 1 1 1 1 1 12 1 0 44 52 0 1 1 1 0 1 1 1 12 1 0 44 52 1 1 1 1 1 0 1 1 12 0 0 48 52 0 1 1 1 1 1 1 1 12 0 0 48 48 0 1 1 1 1 1 1 1 12 . . . . 0 0 1 0 0 0 0 0 12 . . . . 0 0 0 0 0 0 0 0 13 0 1 48 8 0 1 1 1 1 1 1 1 13 0 . 44 . 0 0 1 1 1 1 1 1 13 0 . 32 . 0 0 0 0 0 1 1 1 13 0 . 36 . 0 0 0 0 1 1 1 1 13 0 0 44 8 0 0 1 1 1 1 1 1 13 0 . 24 . 0 0 0 0 0 0 0 1 14 . 0 . 44 0 0 0 0 0 0 0 0 14 1 0 20 44 1 0 0 0 1 1 1 1 14 0 0 52 52 1 1 1 1 1 1 1 1 14 ...... 14 . . . . 0 0 0 0 0 0 0 0 14 . 1 . 4 0 0 0 0 0 0 0 0

199 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

15 0 0 52 52 1 1 1 1 1 1 1 1 15 1 1 44 40 0 1 1 1 0 1 1 1 15 1 1 40 36 0 0 1 1 1 1 0 0 15 0 0 44 44 0 0 1 1 1 1 1 1 15 . . . . 0 0 0 0 1 0 0 0 15 . . . . 0 0 0 0 0 0 0 0 16 0 0 44 52 0 0 1 1 1 1 1 1 16 0 0 40 44 0 0 0 1 1 1 1 1 16 0 0 36 48 0 0 0 0 1 1 1 1 16 0 0 36 40 0 0 0 0 1 1 1 1 16 0 0 28 44 0 0 0 0 0 0 1 1 16 . . . . 0 0 0 0 0 0 0 0 17 0 1 44 16 0 0 1 1 1 1 1 1 17 0 . 44 . 0 0 1 1 1 1 1 1 17 0 . 44 . 0 0 1 1 1 1 1 1 17 0 . 32 . 0 0 0 0 0 1 1 1 17 . . . . 0 0 0 0 0 0 0 0 17 . . . . 0 0 0 0 0 0 0 0 18 . 1 . 48 0 0 0 0 0 0 0 0 18 . 1 . 4 0 0 0 0 0 0 1 0 18 . . . . 0 0 0 0 0 0 0 0 18 . 0 . 52 0 0 0 0 0 1 0 0 18 . . . . 0 0 0 0 0 0 0 0 18 . . . . 0 0 0 0 0 0 0 0 19 0 0 48 24 0 1 1 1 1 1 1 1 19 . . . . 0 0 0 0 0 0 1 0 19 . . . . 0 0 0 0 0 0 0 0 19 . 0 . 20 0 0 0 0 0 0 0 0 19 . 0 . 4 0 0 0 0 0 0 0 0 19 . . . . 0 0 0 0 0 0 0 0 20 0 0 48 52 0 1 1 1 1 1 1 1 20 0 0 52 52 1 1 1 1 1 1 1 1 20 0 0 52 52 1 1 1 1 1 1 1 1 20 0 0 48 52 0 1 1 1 1 1 1 1 20 0 0 48 44 0 1 1 0 1 1 0 1 20 . . . . 0 0 0 0 0 0 0 0 21 1 . 4 . 0 1 0 0 0 0 0 1 21 . . . . 0 1 0 0 0 0 0 1 21 0 0 48 44 0 1 1 1 1 1 1 1 21 ...... 21 0 0 36 44 0 0 0 0 1 1 1 1 21 0 0 52 52 1 1 1 1 1 1 1 1

200 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

22 0 0 52 36 1 1 1 1 1 1 1 1 22 0 . 52 . 1 1 1 1 1 1 1 1 22 0 1 36 24 0 0 1 0 1 1 1 0 22 . . . . 0 0 0 0 0 0 0 0 22 . . . . 0 0 0 0 0 0 0 0 22 . . . . 0 0 0 0 0 0 0 0 23 0 0 40 52 0 0 0 1 1 1 1 1 23 0 1 40 40 0 0 0 1 1 1 1 1 23 0 0 28 36 0 0 0 1 0 0 1 1 23 0 1 40 40 0 0 0 1 1 0 1 1 23 . . . . 0 0 0 0 0 0 0 0 23 . . . . 0 0 0 0 0 0 0 0 24 . . . . 0 0 0 0 0 0 0 0 24 0 . 20 . 0 0 0 0 1 0 1 0 24 . . . . 0 0 0 0 0 0 1 0 24 0 0 44 36 0 0 1 1 1 0 1 1 24 0 0 44 44 0 0 1 1 1 1 1 1 24 . . . . 0 0 0 0 0 0 0 0 25 0 0 48 52 0 1 1 1 1 1 1 1 25 0 0 44 52 0 0 1 1 1 1 1 1 25 0 0 40 52 0 0 0 1 1 1 1 1 25 0 0 40 52 0 0 0 1 1 1 1 1 25 . . . . 0 0 0 0 0 0 1 0 25 0 1 40 28 0 0 0 1 1 0 0 1 26 . 0 . 44 0 0 0 0 0 0 0 0 26 . 0 . 48 0 0 0 0 0 0 0 0 26 . 0 . 48 0 0 0 0 0 0 0 0 26 . 0 . 48 0 0 0 0 0 0 0 0 26 . 0 . 48 0 0 0 0 0 0 0 0 26 . 0 . 48 0 0 0 0 0 0 0 0 27 1 1 44 4 0 1 1 0 0 0 0 1 27 0 . 4 . 0 0 0 0 0 0 0 0 27 0 . 20 . 0 0 0 0 0 1 0 0 27 0 0 44 36 0 0 1 1 1 1 1 1 27 0 0 36 36 0 0 0 0 1 1 1 1 27 . . . . 0 0 0 0 0 0 0 0 28 0 0 52 48 1 1 1 1 1 1 1 1 28 0 0 52 48 1 1 1 1 1 1 1 1 28 0 0 52 48 1 1 1 1 1 1 1 1 28 0 0 52 48 1 1 1 1 0 1 1 1 28 0 1 28 44 0 0 0 0 1 0 1 1 28 . . . . 0 0 0 0 0 0 0 0

201 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

29 0 0 52 48 1 1 1 1 1 1 1 1 29 . . . . 0 1 0 0 0 0 0 0 29 0 0 52 44 1 1 1 1 1 1 1 1 29 0 0 52 44 1 1 1 1 1 1 1 1 29 0 0 44 44 1 0 1 1 1 1 1 1 29 . 1 . 24 0 1 0 0 0 1 0 0 30 . 0 . 52 0 0 0 0 0 0 0 0 30 0 0 52 48 1 1 1 1 1 1 1 1 30 ...... 30 0 0 44 36 1 0 1 1 1 1 1 1 30 . . . . 0 0 0 0 0 0 0 0 30 . . . . 0 0 0 0 0 0 0 0 31 . . . . 0 1 0 1 0 0 1 0 31 . . . . 0 1 0 1 0 0 1 0 31 ...... 31 0 0 40 24 0 0 0 1 1 0 1 0 31 . . . . 0 0 0 0 0 0 0 1 31 . . . . 0 0 0 0 0 0 0 0 32 0 1 52 28 1 1 1 1 1 1 1 1 32 0 . 44 . 0 0 1 1 1 1 1 1 32 0 . 52 . 1 1 1 1 1 1 1 1 32 0 . 48 . 0 1 1 1 1 1 1 1 32 0 . 32 . 0 0 0 0 0 1 1 0 32 . . . . 0 0 0 0 0 0 0 0 33 1 0 16 52 0 0 0 0 1 1 0 1 33 . 0 . 48 0 0 0 0 0 0 0 0 33 . 0 . 52 0 0 0 0 0 0 0 0 33 . 0 . 48 0 0 0 0 0 0 0 0 33 . 0 . 48 0 0 0 0 0 0 0 0 33 . . . . 0 0 0 0 0 0 0 0 34 . 0 . 52 0 0 0 0 0 0 1 0 34 . 0 . 52 0 1 0 0 0 0 0 1 34 1 0 32 52 0 0 1 0 1 1 1 1 34 . 0 . 24 0 0 0 0 0 0 0 0 34 . . . . 0 0 0 0 0 0 0 0 34 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0 35 . . . . 0 0 0 0 0 0 0 0

202 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

36 0 0 44 12 0 0 1 1 1 1 1 1 36 . . . . 0 0 0 0 0 0 0 0 36 0 . 36 . 0 0 0 0 1 1 0 1 36 0 0 40 4 0 0 0 1 1 1 1 1 36 0 . 24 . 0 0 0 0 0 0 0 1 36 0 . 8 . 0 0 0 0 0 0 0 0 37 . 0 . 28 0 0 0 0 0 0 0 0 37 . 0 . 4 0 0 0 0 0 0 0 0 37 . 0 . 28 0 0 0 0 0 0 0 0 37 . 0 . 36 0 0 0 0 0 0 0 0 37 . 1 . 28 0 0 0 0 0 0 0 0 37 . . . . 0 0 0 0 0 0 0 0 38 0 . 12 . 0 0 0 0 0 0 0 0 38 . . . . 0 0 0 0 0 0 0 0 38 . . . . 0 0 0 0 0 0 0 0 38 . . . . 0 0 0 0 0 0 0 0 38 . . . . 0 0 0 0 0 0 0 0 38 . . . . 0 0 0 0 0 0 0 0 39 0 0 52 36 1 1 1 1 1 1 1 1 39 0 . 20 . 0 1 0 0 1 0 0 0 39 0 . 40 . 0 0 0 1 1 1 1 0 39 0 1 44 4 0 0 1 1 1 0 1 0 39 . . . . 1 0 0 0 0 0 0 0 39 . . . . 0 1 0 0 0 0 0 0 40 ...... 40 0 0 24 44 0 0 0 0 0 0 0 1 40 0 0 20 44 0 0 0 0 0 0 0 0 40 0 0 20 40 0 0 0 0 0 0 0 0 40 0 0 16 36 0 0 0 0 0 0 0 0 40 . . . . 0 0 0 0 0 0 0 0 41 0 1 32 32 0 0 0 0 0 1 1 1 41 0 0 44 48 0 0 1 1 1 1 1 1 41 0 0 44 44 0 0 1 1 1 1 1 1 41 0 0 48 48 0 1 1 1 1 1 1 1 41 . . . . 0 0 0 0 0 0 0 0 41 . . . . 0 0 0 0 0 0 0 0 42 0 0 52 48 1 1 1 1 1 1 1 1 42 0 0 48 44 0 1 1 1 1 1 1 1 42 0 0 52 48 1 1 1 1 1 1 1 1 42 0 0 52 48 1 1 1 1 1 1 1 1 42 0 0 44 48 0 0 1 1 1 0 0 0 42 . . 4 0 0 0 0 0 0 0 0

203 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

43 1 1 32 36 1 1 1 1 1 1 1 1 43 1 1 24 8 1 1 0 0 0 1 1 0 43 . 1 . 8 0 0 1 0 0 1 0 1 43 1 1 4 32 0 1 0 1 0 0 1 1 43 . 1 . 12 0 0 0 0 0 0 0 0 43 . 1 . 20 0 0 0 0 0 0 0 0 44 0 0 52 52 1 1 1 1 1 1 1 1 44 0 0 48 52 0 1 1 1 1 1 1 1 44 0 0 48 52 0 1 1 1 1 1 1 1 44 0 0 44 48 0 0 1 1 1 1 1 1 44 0 0 36 48 0 0 0 0 1 1 1 1 44 0 0 28 52 0 0 0 0 0 0 1 1 45 0 . 32 . 0 0 0 0 0 1 1 1 45 . . . . 0 0 0 0 0 0 0 0 45 0 . 28 . 0 0 0 0 0 0 1 1 45 . . . . 0 0 0 0 0 0 0 0 45 . . . . 0 0 0 0 0 0 0 0 45 . . . . 0 0 0 0 0 0 0 0 46 0 0 52 44 1 1 1 1 1 1 1 1 46 0 0 52 48 1 1 1 1 1 1 1 1 46 . . . . 0 0 0 0 0 0 0 0 46 0 0 48 52 0 1 1 1 1 1 1 1 46 . . . . 0 0 0 0 0 0 0 0 46 . . . . 0 0 0 0 0 0 0 0 47 0 0 44 52 1 0 1 1 1 1 1 1 47 0 0 40 48 0 0 0 1 1 1 1 1 47 0 0 44 48 0 0 1 1 1 1 1 1 47 0 0 44 48 0 0 1 1 1 1 1 1 47 . . . . 0 0 0 0 0 0 0 0 47 . . . . 0 0 0 0 0 0 0 0 48 1 0 16 44 0 0 1 1 1 1 1 0 48 . 0 . 44 0 0 0 0 0 0 0 0 48 . 1 . 20 0 0 0 0 0 0 0 0 48 . 0 . 40 0 0 0 0 0 0 0 0 48 . . . . 0 0 0 0 0 0 0 0 48 . . . . 0 0 0 0 0 0 0 0 49 0 0 40 52 0 1 0 1 1 1 1 1 49 0 0 48 52 0 1 1 1 1 1 1 1 49 0 0 48 52 0 1 1 1 1 1 1 1 49 0 0 48 48 0 1 1 1 1 1 1 1 49 0 0 44 48 0 0 1 1 1 1 1 1 49 0 0 36 48 0 0 0 0 1 1 1 1

204 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

50 0 0 52 52 1 1 1 1 1 1 1 1 50 0 0 52 48 1 1 1 1 1 1 1 1 50 0 0 52 52 1 1 1 1 1 1 1 1 50 0 0 52 48 1 1 1 1 1 1 1 1 50 0 0 52 40 1 1 1 1 1 1 1 1 50 0 0 44 40 0 0 1 1 1 1 1 1 51 0 0 52 44 1 1 1 0 1 1 1 1 51 1 0 8 52 1 1 1 0 0 0 0 0 51 . . . . 0 0 0 0 0 0 0 0 51 0 0 8 52 0 0 0 0 0 0 0 0 51 . . . . 0 0 0 0 0 0 0 0 51 . . . . 0 0 0 0 0 0 0 0 52 0 0 52 44 1 1 1 1 1 1 1 1 52 0 0 48 40 0 1 1 1 1 1 1 1 52 0 0 48 40 0 1 1 1 1 1 1 1 52 0 0 48 4 0 1 1 1 1 1 1 1 52 1 . 4 . 0 0 0 0 1 0 0 1 52 . . . . 0 0 0 0 0 0 0 0 53 0 0 52 52 1 1 1 1 1 1 1 1 53 0 0 52 48 1 1 1 1 1 1 1 1 53 0 0 52 48 1 1 1 1 1 1 1 1 53 0 0 52 52 1 1 1 1 1 1 1 1 53 0 0 52 48 1 1 1 1 1 1 1 1 53 0 0 52 48 1 1 1 1 1 1 1 1 54 0 0 52 52 1 1 1 1 1 1 1 1 54 0 1 52 4 1 1 1 1 1 1 1 1 54 ...... 54 0 0 52 44 1 1 1 1 1 1 1 1 54 . . . . 0 0 0 0 0 0 0 0 54 . . . . 0 0 0 0 0 0 0 0 55 0 0 44 52 0 0 1 1 1 1 1 1 55 1 . 24 . 0 0 1 1 0 1 0 1 55 0 0 44 48 0 0 1 1 1 1 1 1 55 ...... 55 0 1 44 28 0 0 1 1 1 1 1 1 55 0 1 36 16 0 0 0 0 1 1 1 1 56 0 0 48 52 0 1 1 1 1 1 1 1 56 0 0 40 52 0 1 0 1 1 1 1 1 56 0 0 52 48 1 1 1 0 1 1 1 1 56 0 0 52 48 1 1 1 1 1 1 1 1 56 0 . 4 . 0 1 0 1 0 0 0 0 56 . . . . 0 0 0 0 0 0 0 0

205 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

57 0 0 52 48 1 1 1 1 1 1 1 1 57 1 . 4 . 0 1 0 0 0 0 0 0 57 1 0 4 44 0 0 0 0 1 0 0 0 57 0 0 40 44 0 0 0 1 1 1 0 1 57 0 . 24 . 0 0 1 0 0 0 0 1 57 . . . . 0 0 1 0 0 0 0 0 58 0 1 40 36 0 1 0 1 1 1 1 1 58 0 0 8 24 0 0 0 0 0 0 0 0 58 0 1 24 24 0 0 0 0 0 1 0 1 58 0 0 32 36 0 0 0 1 0 1 1 1 58 . . . . 0 0 0 0 0 0 1 0 58 . . . . 0 0 0 0 0 0 0 0 59 0 0 52 52 1 1 1 1 1 1 1 1 59 0 0 52 40 1 1 1 1 1 1 1 1 59 0 0 52 40 1 1 1 1 1 1 1 1 59 0 0 52 40 1 1 1 1 1 1 1 1 59 0 0 52 44 1 1 1 1 1 1 1 1 59 . . . . 0 0 0 0 0 0 0 0 60 0 0 48 52 0 1 1 1 1 1 1 1 60 . 1 . 12 0 1 0 0 1 0 1 0 60 0 0 36 48 0 0 1 0 1 1 1 1 60 0 0 40 48 0 0 0 1 1 1 1 1 60 0 0 44 48 0 0 1 1 1 1 1 1 60 0 0 48 8 0 1 1 0 0 0 1 1 61 0 0 52 44 1 1 1 1 1 1 1 1 61 0 1 48 32 0 1 1 1 1 1 1 1 61 0 0 44 40 0 0 1 1 1 1 1 1 61 0 0 44 40 0 0 1 1 1 1 1 1 61 . . . . 0 0 0 0 0 0 0 0 61 . . . . 0 0 0 0 0 0 0 0 62 0 0 48 52 0 1 1 1 1 1 1 1 62 0 0 52 52 1 1 1 1 1 1 1 1 62 0 0 52 44 1 1 1 1 1 1 1 1 62 0 0 52 48 1 1 1 1 1 1 1 1 62 0 0 52 48 1 1 1 1 1 1 1 1 62 0 0 52 44 1 1 1 1 1 1 1 1 63 0 0 20 52 0 0 0 0 0 0 1 0 63 . 0 . 48 0 0 0 0 0 0 0 0 63 . 0 . 48 0 0 0 0 0 0 0 0 63 . 0 . 44 0 0 0 0 0 0 0 0 63 . . . . 0 0 0 0 0 0 0 0 63 . . . . 0 0 0 0 0 0 0 0

206 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

64 0 0 48 52 0 1 1 1 1 0 1 1 64 0 0 52 48 1 1 1 1 1 1 1 0 64 . 0 . 16 0 0 1 0 0 0 1 0 64 0 0 44 48 0 0 1 1 1 1 1 0 64 0 0 44 40 0 0 1 1 1 1 0 0 64 . 0 . 44 0 0 0 0 0 0 0 0 65 1 . 28 . 0 0 0 1 0 1 1 1 65 0 0 52 52 1 1 1 1 1 1 1 1 65 1 1 40 36 1 0 1 1 1 0 1 0 65 0 0 44 48 0 0 1 1 1 1 1 1 65 0 0 40 48 0 0 0 1 1 1 1 1 65 0 1 44 4 0 0 1 1 1 1 1 1 66 0 0 52 52 1 1 1 1 1 1 1 1 66 0 0 48 52 0 1 1 1 1 1 1 1 66 0 0 40 52 0 0 0 1 1 1 1 1 66 0 0 44 52 0 0 1 1 1 1 1 1 66 0 0 40 48 0 0 0 1 1 1 1 1 66 0 0 40 44 0 0 0 1 1 1 1 1 67 0 0 44 40 0 0 1 1 1 1 1 1 67 0 0 40 40 0 0 0 1 1 1 1 1 67 0 0 36 40 0 0 0 0 1 1 1 1 67 0 0 36 40 0 0 0 0 1 1 1 1 67 . . . . 0 0 0 0 0 0 0 0 67 0 0 20 16 0 0 0 0 0 0 0 0 68 0 0 52 52 1 1 1 1 1 1 1 1 68 . 0 . 52 0 0 0 0 1 0 0 0 68 . 0 . 52 0 1 0 0 0 1 0 0 68 0 0 52 52 1 1 1 0 0 1 1 1 68 . . . . 0 0 0 0 0 0 0 0 68 . . . . 0 0 0 0 0 0 0 0 69 0 0 52 52 1 1 1 1 1 1 1 1 69 0 0 48 44 0 1 1 1 1 1 1 1 69 0 0 52 44 1 1 1 1 1 1 1 1 69 0 0 48 40 0 1 1 1 1 1 1 1 69 . 1 . 4 0 0 1 0 0 0 0 0 69 . . . . 0 0 0 0 0 0 0 0 70 1 . 24 . 0 0 1 1 0 1 1 0 70 . 1 . 24 0 0 0 0 0 0 0 0 70 . 0 . 12 0 0 0 0 0 0 0 0 70 . 0 . 48 0 0 0 0 0 0 1 0 70 . 0 . 44 0 0 0 0 0 0 0 0 70 . . . . 0 0 0 0 0 0 0 0

207 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

71 0 1 52 32 1 1 1 1 1 1 1 1 71 0 0 44 52 0 0 1 1 1 1 1 1 71 0 0 52 52 1 1 1 1 1 1 1 1 71 0 0 44 40 0 0 1 1 1 1 1 1 71 0 . 4 . 0 0 0 0 0 0 0 0 71 . . . . 0 0 0 0 0 0 0 0 72 0 0 48 40 0 1 1 1 1 1 1 1 72 0 0 40 32 0 0 0 1 1 0 0 0 72 0 0 12 28 0 1 0 1 0 0 0 1 72 1 0 44 48 0 1 1 1 0 0 1 0 72 0 0 16 24 0 0 0 0 0 0 1 0 72 . 1 . 12 0 0 0 0 0 0 0 0 73 0 1 52 44 1 1 1 1 1 1 1 1 73 0 0 48 52 0 1 1 1 1 1 1 1 73 0 1 40 4 0 0 0 1 1 1 1 1 73 0 1 44 24 0 0 1 1 1 1 1 1 73 . . . . 0 0 0 0 0 0 0 0 73 . . . . 0 0 0 0 0 0 0 0 74 0 0 48 52 0 1 1 1 1 1 1 1 74 0 0 44 48 0 0 1 1 1 1 1 1 74 0 0 36 48 0 0 1 0 1 1 1 1 74 0 0 44 48 0 0 1 1 1 1 1 1 74 0 0 44 48 0 0 1 1 1 1 1 1 74 0 0 32 40 0 0 1 0 0 1 1 1 75 0 0 52 44 1 1 1 1 1 1 1 1 75 0 . 28 . 0 0 0 0 0 0 1 1 75 0 0 52 52 1 1 1 1 1 1 1 1 75 0 0 52 52 1 1 1 1 1 1 1 1 75 0 0 52 48 1 1 1 1 1 1 1 0 75 0 0 52 40 1 1 1 1 1 1 1 1 76 1 0 12 32 0 0 0 0 0 0 0 0 76 1 . 40 . 0 1 1 1 1 1 1 1 76 . . . . 0 0 0 0 0 0 0 0 76 0 . 36 . 0 0 0 0 1 1 1 1 76 . . . . 0 0 0 0 0 0 0 0 76 . . . . 0 0 0 0 0 0 0 0 77 0 . 44 . 0 0 1 1 1 1 1 1 77 0 . 20 . 0 0 0 0 0 0 0 0 77 0 . 40 . 0 0 0 1 1 1 1 1 77 0 . 36 . 0 0 0 0 1 1 1 1 77 0 0 40 4 0 0 0 1 1 1 1 1 77 0 . 20 . 0 0 0 0 0 0 0 0

208 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

78 0 0 52 52 1 1 1 1 1 1 1 1 78 0 0 48 52 0 1 1 1 1 1 1 1 78 0 0 48 52 0 1 1 1 1 1 1 1 78 0 0 44 44 0 0 1 1 1 1 1 1 78 0 0 40 28 0 1 0 1 1 1 0 0 78 . 0 . 20 0 0 0 0 0 0 0 0 79 0 0 52 52 1 1 1 1 1 1 1 1 79 0 0 48 48 0 1 1 1 1 1 1 1 79 0 0 48 48 0 1 1 1 1 1 1 1 79 0 0 48 48 0 1 1 1 1 1 1 1 79 0 0 36 48 0 0 0 0 1 1 1 1 79 0 0 32 48 0 0 0 0 0 1 1 1 80 0 0 52 52 1 1 0 1 1 1 1 1 80 0 0 52 52 1 1 1 1 1 1 1 1 80 0 0 52 52 1 1 0 1 1 1 1 1 80 0 0 52 52 1 1 1 1 1 1 1 1 80 0 0 8 44 1 0 0 0 0 1 0 0 80 0 1 44 8 1 0 1 1 0 0 0 0 81 1 0 12 48 0 0 1 1 1 1 0 0 81 . 1 . 8 0 0 0 0 0 0 1 0 81 . . . . 1 0 0 0 0 0 0 1 81 0 0 40 48 0 0 0 1 1 1 1 1 81 . . . . 0 0 0 0 0 0 0 0 81 . . . . 0 0 0 0 0 0 0 0 82 0 0 52 44 1 1 1 1 1 1 1 1 82 0 0 36 36 0 0 0 0 1 1 1 1 82 0 0 52 40 1 1 1 1 1 1 1 1 82 0 0 28 40 0 0 0 0 0 0 1 1 82 0 1 48 32 0 1 1 1 1 1 1 1 82 0 . 20 . 0 0 0 0 1 0 0 0 83 0 0 36 52 0 0 0 0 1 1 1 1 83 0 1 28 24 0 0 0 1 0 0 1 1 83 0 0 44 44 0 0 1 1 1 1 1 1 83 0 0 40 40 0 0 0 1 1 1 1 1 83 1 . 4 . 0 0 0 0 0 1 0 0 83 . . . . 0 0 0 0 0 0 0 0 84 0 1 52 16 1 1 1 1 1 1 1 1 84 1 1 48 12 1 1 1 1 1 1 1 1 84 1 1 44 20 1 1 1 1 1 1 1 1 84 1 1 32 20 1 1 1 1 1 1 1 1 84 1 . 4 . 1 1 0 0 0 0 0 0 84 . . . . 0 0 0 0 0 0 0 0

209 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

85 0 0 48 52 0 1 1 1 1 1 1 1 85 0 0 48 48 0 1 1 1 1 1 1 1 85 ...... 85 0 1 44 44 0 0 1 1 1 1 1 1 85 . . . . 0 0 0 0 0 0 0 0 85 . . . . 0 0 0 0 0 0 0 0 86 1 0 44 44 0 1 1 1 1 1 1 1 86 1 0 12 44 0 0 0 0 0 1 1 1 86 . 0 . 28 0 0 0 0 0 0 0 0 86 0 0 32 40 0 0 0 0 0 1 1 1 86 . . . . 0 0 0 0 0 0 0 1 86 0 0 36 40 0 0 0 0 1 1 1 1 87 0 0 52 52 1 1 1 1 1 1 1 1 87 . . . . 0 0 0 0 0 0 0 0 87 . 0 . 48 0 0 0 0 0 0 0 0 87 . 0 . 8 0 0 0 0 0 0 0 0 87 . 1 . 8 0 0 0 0 0 0 0 0 87 . . . . 0 0 0 0 0 0 0 0 88 1 . 24 . 1 1 0 1 0 0 1 0 88 1 0 44 52 1 1 1 1 1 0 1 1 88 0 0 52 52 1 1 1 1 1 0 1 1 88 0 0 52 52 1 1 1 1 1 1 1 1 88 . . . . 0 0 0 0 0 0 0 0 88 . . . . 0 0 0 0 0 0 0 0 89 0 1 32 32 0 0 0 0 0 1 1 1 89 0 . 24 . 0 0 0 0 0 0 0 1 89 0 0 28 32 0 0 0 0 0 0 1 1 89 0 1 18 4 0 0 0 0 0 0 0 0 89 . . . . 0 0 0 0 0 0 0 0 89 . . . . 0 0 0 0 0 0 0 0 90 0 0 52 48 1 1 1 1 1 1 1 1 90 . . . . 0 0 0 0 0 0 0 0 90 0 0 44 48 0 0 1 1 1 1 1 1 90 0 0 44 48 0 0 1 1 1 1 1 1 90 0 0 44 48 0 0 1 1 1 1 1 1 90 0 0 44 48 0 0 1 1 1 1 1 0 91 1 0 28 44 0 0 0 1 0 1 1 1 91 . . . . 0 0 0 0 0 0 0 0 91 1 0 24 40 0 0 1 0 0 0 1 1 91 . . . . 0 0 0 0 0 0 0 1 91 . . . . 0 0 0 0 0 0 0 0 91 . . . . 0 0 0 0 0 0 0 0

210 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

92 0 0 52 52 1 1 1 1 1 1 1 1 92 0 0 52 48 1 1 1 1 1 1 1 1 92 0 0 16 44 0 0 1 0 0 0 1 0 92 0 0 44 44 0 0 1 1 1 1 1 1 92 0 0 36 44 0 0 1 0 1 1 1 1 92 1 . 12 . 0 0 0 1 1 0 1 0 93 1 0 8 52 0 0 1 0 1 0 0 1 93 0 0 40 48 0 0 0 1 1 1 1 1 93 0 0 44 52 0 0 1 1 1 1 1 1 93 0 0 40 52 0 0 0 1 1 1 1 1 93 0 0 40 52 0 0 0 1 1 1 1 1 93 . . . . 0 0 0 0 0 0 0 0 94 . 1 . 32 0 0 0 0 0 0 0 0 94 . 0 . 40 0 0 0 0 0 0 0 0 94 . 0 . 4 0 0 0 0 0 0 0 0 94 . 0 . 32 0 0 0 0 0 0 0 0 94 . . . . 0 0 0 0 0 0 0 0 94 . . . . 0 0 0 0 0 0 0 0 95 . . . . 1 0 0 0 0 0 0 0 95 . . . . 0 0 0 0 0 0 0 0 95 0 0 32 36 0 0 0 0 0 1 1 1 95 0 0 32 36 0 0 0 0 0 1 1 1 95 . . . . 0 0 0 0 0 0 0 0 95 . . . . 0 0 0 0 0 0 0 0 96 1 0 36 40 1 1 1 1 0 1 1 0 96 1 . 32 . 1 1 0 0 0 0 0 0 96 ...... 96 0 0 52 48 1 1 1 1 1 1 1 1 96 . . . . 0 0 0 0 0 0 0 0 96 . . . . 0 0 0 0 0 0 0 0 97 0 0 52 52 1 1 1 1 1 1 1 1 97 0 . 44 . 0 0 1 1 1 1 1 1 97 0 0 44 28 1 0 1 1 1 1 1 1 97 0 1 44 4 0 0 1 1 1 1 1 1 97 0 0 52 52 1 1 1 1 1 1 1 1 97 0 . 12 . 0 0 1 0 0 0 0 0 98 1 0 44 52 1 1 1 1 1 1 1 1 98 . 1 . 12 0 0 0 0 0 1 0 1 98 ...... 98 1 0 36 40 0 0 0 1 1 1 0 1 98 . . . . 0 0 0 0 0 0 0 0 98 . . . . 0 0 0 0 0 0 0 0

211 SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33 # time of last 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ last 80 reading time of first is before 60 min 80 reading ded if onset occurs

99 0 0 52 52 1 1 1 1 1 1 1 1 99 0 1 52 20 1 1 1 1 1 1 1 0 99 0 1 52 28 1 1 1 1 1 1 0 1 99 . 1 . 4 0 0 0 0 0 0 0 0 99 . . . . 0 0 0 0 0 0 0 0 99 . . . . 0 0 0 0 0 1 0 0 100 0 0 52 48 1 1 1 1 1 1 1 1 100 0 0 52 52 1 1 1 1 1 1 1 1 100 0 0 48 52 0 1 1 1 1 1 1 1 100 0 0 48 52 0 1 1 1 1 1 1 1 100 0 0 48 52 0 1 1 1 1 1 1 1 100 . . . . 0 0 0 0 0 1 0 0

212 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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213 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

8 1 1 1 1 1 1 0 0 0 0 1 1 1 1 8 1 1 1 1 1 1 0 0 0 1 0 0 1 1 8 1 1 1 1 1 1 0 0 0 0 1 0 1 1 8 1 1 1 1 1 1 0 0 0 0 0 1 1 1 8 0 1 0 0 0 0 0 0 0 0 0 0 0 0 8 0 0 1 0 0 0 0 0 0 0 0 0 0 0 9 1 1 1 1 1 1 1 0 1 1 1 1 0 0 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10 0 0 0 0 1 1 0 0 0 0 0 0 0 0 10 0 0 0 0 1 1 0 0 0 0 0 0 0 0 10 1 1 1 1 1 1 0 0 0 0 0 0 0 0 10 1 1 1 1 1 1 0 0 0 0 0 0 0 0 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 0 1 0 0 0 1 0 0 0 0 0 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 0 1 1 1 1 1 1 1 11 1 1 1 1 1 1 0 0 1 1 0 1 1 1 12 1 1 1 1 1 0 1 1 1 1 1 1 1 1 12 1 0 1 1 0 0 1 1 1 1 1 1 1 1 12 1 1 1 1 1 1 1 1 1 1 1 1 1 1 12 1 1 1 1 1 1 0 1 1 1 1 1 1 1 12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 13 1 1 1 1 1 1 0 0 0 0 0 0 1 1 13 1 1 1 1 1 1 0 0 0 0 0 0 0 0 13 1 1 1 1 1 1 0 0 0 0 0 0 0 0 13 1 1 1 1 1 1 0 0 0 0 0 0 0 0 13 1 1 1 1 1 1 0 0 0 0 0 0 0 0 13 1 1 1 1 0 1 0 0 0 0 0 0 0 0 14 0 0 0 0 0 0 1 0 1 1 0 0 0 1 14 1 1 0 0 0 0 0 0 1 1 0 0 0 0 14 1 1 1 1 1 1 1 1 1 1 1 1 1 1 14 ...... 14 0 0 0 0 0 0 0 0 1 0 0 0 0 0 14 0 0 0 0 0 0 1 1 0 0 0 0 0 0

214 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

15 1 1 1 1 1 1 1 1 1 1 1 1 1 1 15 1 1 1 1 1 0 0 0 1 1 1 0 1 0 15 1 1 1 1 1 0 0 0 0 1 1 1 1 1 15 1 1 1 1 1 1 0 0 1 1 1 1 1 1 15 0 0 0 1 0 0 0 0 0 0 0 1 0 0 15 0 0 0 0 0 0 0 0 0 0 0 0 0 0 16 1 1 1 1 1 1 1 1 1 1 1 1 1 1 16 1 1 1 1 1 1 0 0 1 1 1 1 1 1 16 1 1 1 1 1 1 0 1 1 1 1 1 1 1 16 1 1 1 1 1 1 0 0 0 1 1 1 1 1 16 1 0 0 1 1 1 0 0 1 1 1 1 1 1 16 0 0 0 0 0 0 0 0 0 0 1 0 0 0 17 1 1 1 1 1 1 0 0 0 0 1 1 1 1 17 1 1 1 1 1 1 0 0 0 0 0 0 0 0 17 1 1 1 1 1 1 0 0 0 0 0 0 0 0 17 1 1 1 1 1 1 0 0 0 0 0 0 0 0 17 0 0 0 0 0 0 0 0 0 0 0 0 0 0 17 0 0 0 0 0 0 0 0 0 0 0 0 0 0 18 0 0 0 0 0 0 1 1 1 1 1 0 1 1 18 0 0 0 0 0 1 0 0 0 0 0 0 0 1 18 0 0 0 0 0 0 0 0 0 0 0 0 0 0 18 0 0 0 0 0 0 1 1 1 1 0 0 0 1 18 0 0 0 0 0 0 0 0 0 0 0 0 0 0 18 0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 1 1 1 1 1 1 0 1 0 0 0 1 0 1 19 0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 0 0 0 0 0 0 0 0 0 0 0 0 0 0 20 1 1 1 1 1 1 1 1 1 1 1 1 1 1 20 1 1 1 1 1 1 1 1 1 1 1 1 1 1 20 1 1 1 1 1 1 1 1 1 1 1 1 1 1 20 1 1 1 1 1 1 1 1 1 1 1 1 1 1 20 1 1 1 1 0 1 0 0 1 1 1 1 1 1 20 0 0 0 0 0 0 0 0 0 0 0 0 0 0 21 1 0 0 0 0 0 0 0 0 0 0 0 0 0 21 0 0 0 1 0 1 0 0 0 0 0 0 0 0 21 1 1 1 1 1 1 0 0 1 1 1 1 1 1 21 ...... 21 1 1 1 1 1 1 0 0 1 1 1 1 1 1 21 1 1 1 1 1 1 1 1 1 1 1 1 1 1

215 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

22 1 1 1 1 1 1 0 0 0 0 1 1 1 1 22 1 1 1 1 1 1 0 0 0 0 0 0 0 0 22 1 1 0 1 0 1 0 0 0 0 1 0 1 1 22 0 0 0 0 0 0 0 0 0 0 0 0 0 0 22 0 1 0 0 0 0 0 0 0 0 0 0 0 0 22 0 0 0 0 0 0 0 0 0 0 0 0 0 0 23 1 1 1 1 1 1 1 1 1 1 1 1 1 1 23 0 1 1 1 1 1 0 0 1 1 1 1 1 1 23 1 1 1 1 1 1 0 0 0 0 1 1 1 1 23 0 1 1 1 1 1 0 0 1 1 1 0 1 1 23 0 0 0 0 0 0 0 0 0 0 0 0 0 0 23 0 0 0 0 0 0 0 0 0 0 0 0 0 0 24 0 0 0 0 0 0 0 0 0 0 0 0 0 0 24 1 1 0 0 0 1 0 0 0 0 0 1 0 0 24 0 0 0 1 0 1 0 0 0 0 1 0 0 1 24 1 1 1 1 1 1 0 0 0 0 1 1 1 1 24 1 1 1 1 1 1 0 0 1 1 1 1 1 1 24 0 0 0 0 0 0 0 0 0 0 0 0 0 0 25 1 1 1 1 1 1 1 1 1 1 1 1 1 1 25 1 1 1 1 1 1 1 1 1 1 1 1 1 1 25 1 1 1 1 1 1 1 1 1 1 1 1 1 1 25 1 1 1 1 1 1 1 1 1 1 1 1 1 1 25 0 0 1 0 0 0 1 0 0 0 0 0 0 0 25 0 1 1 1 1 1 0 0 0 0 1 1 0 0 26 0 0 0 0 0 0 0 0 1 1 1 1 1 1 26 0 0 0 0 0 0 0 1 1 1 1 1 1 1 26 0 0 0 0 0 0 0 1 1 1 1 1 1 1 26 0 0 0 0 0 0 0 1 1 1 1 1 1 1 26 0 0 0 0 0 0 0 1 1 1 1 1 1 1 26 0 0 0 0 0 0 0 1 1 1 1 1 1 1 27 0 0 0 1 1 0 0 0 0 0 0 0 0 0 27 0 0 0 0 1 1 0 0 0 0 1 0 0 0 27 1 1 1 1 1 1 0 0 0 0 0 0 0 0 27 1 1 1 1 1 1 0 0 0 0 1 1 1 1 27 1 1 1 1 1 1 0 0 0 0 1 1 1 1 27 0 0 0 0 0 0 0 0 0 0 0 0 0 0 28 1 1 1 1 1 1 0 1 1 1 1 1 1 1 28 1 1 1 1 1 1 0 1 1 1 1 1 1 1 28 1 1 1 1 1 1 0 1 1 1 1 1 1 1 28 1 1 1 1 1 1 0 1 1 1 1 1 1 1 28 1 1 0 1 1 1 0 1 1 1 1 1 1 1 28 0 0 0 1 0 0 0 0 0 0 0 0 0 0

216 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

29 1 1 1 0 0 1 0 1 1 1 1 1 1 1 29 0 0 0 0 0 0 0 0 0 0 0 1 0 0 29 1 1 1 1 1 1 0 0 1 1 1 1 1 1 29 1 1 1 1 1 1 0 0 1 1 1 1 1 1 29 1 1 1 1 1 1 1 0 1 1 1 1 1 1 29 0 0 1 0 0 0 1 1 0 0 1 0 1 0 30 0 0 0 0 0 0 1 1 1 1 1 1 1 1 30 1 1 1 1 1 1 0 1 1 1 1 1 1 1 30 ...... 30 1 1 1 1 1 1 0 0 0 0 1 1 1 1 30 0 0 0 0 0 0 0 0 0 0 0 0 0 0 30 0 0 0 0 0 0 0 0 0 0 0 0 0 0 31 0 0 0 0 0 0 0 0 0 0 0 0 0 0 31 0 0 0 0 0 0 0 0 0 0 0 0 0 0 31 ...... 31 0 1 1 1 1 1 0 0 0 0 0 0 0 1 31 0 1 0 0 0 0 0 0 0 0 0 0 0 0 31 0 0 0 0 0 0 0 0 0 0 0 0 0 0 32 1 1 1 1 1 1 0 0 0 0 1 1 0 1 32 1 0 1 1 1 1 0 0 0 0 0 0 0 0 32 1 1 1 1 1 1 0 0 0 0 0 0 0 0 32 1 1 1 1 1 1 0 0 0 0 0 1 0 0 32 0 0 1 0 1 1 0 0 0 0 0 0 0 0 32 0 0 0 0 0 0 0 0 0 0 0 0 0 0 33 1 0 0 0 0 0 1 1 1 1 1 1 1 1 33 0 0 0 0 0 0 0 1 1 1 1 1 1 1 33 0 0 0 0 0 0 1 1 1 1 1 1 1 1 33 0 0 0 0 0 0 0 1 1 1 1 1 1 1 33 0 0 0 0 0 0 0 1 1 1 1 1 1 1 33 0 0 0 0 0 0 0 0 0 0 0 0 0 0 34 0 1 0 0 0 0 1 1 1 1 1 1 1 1 34 0 0 0 0 1 0 1 1 1 1 1 1 1 1 34 1 0 0 0 1 0 1 1 1 1 1 1 1 1 34 0 0 0 1 0 0 0 0 0 0 0 1 0 1 34 0 0 0 1 0 0 0 0 0 0 0 0 0 0 34 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0 35 0 0 0 0 0 0 0 0 0 0 0 0 0 0

217 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

36 1 1 1 1 1 1 0 0 0 0 0 0 0 0 36 0 0 0 1 0 1 0 0 0 0 0 0 0 0 36 0 1 1 1 1 1 0 0 0 0 0 0 0 0 36 1 1 1 1 1 1 0 0 0 0 0 0 0 0 36 1 1 0 0 0 1 0 0 0 0 0 0 0 0 36 0 0 0 0 1 1 0 0 0 0 0 0 0 0 37 0 1 0 1 0 1 0 0 0 0 1 0 1 1 37 0 0 0 0 0 0 0 0 0 0 0 0 0 0 37 0 0 0 0 0 0 0 0 0 0 0 0 1 1 37 0 0 0 0 0 0 0 0 0 0 1 1 1 1 37 0 0 0 0 0 0 0 0 0 1 1 0 0 0 37 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 0 0 1 1 0 1 0 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 0 0 0 0 0 0 0 38 0 0 0 0 0 0 0 0 0 0 0 0 0 0 39 1 1 1 1 1 1 1 0 1 0 1 1 1 1 39 1 1 1 1 1 1 0 0 0 0 0 0 0 0 39 1 1 1 1 1 1 0 0 0 0 0 0 1 0 39 1 1 1 1 0 1 0 0 0 0 0 0 0 0 39 0 0 0 0 0 1 0 0 0 0 0 0 0 0 39 0 0 0 0 0 0 0 0 0 0 0 0 0 0 40 ...... 40 1 1 1 1 1 1 0 0 1 1 1 1 1 1 40 1 1 1 1 1 1 0 0 1 1 1 1 1 1 40 1 1 1 1 1 1 0 0 0 1 1 1 1 1 40 0 1 1 1 1 1 0 0 0 0 1 1 1 1 40 0 0 0 0 0 1 0 0 0 0 0 0 0 0 41 1 1 1 1 1 1 0 1 1 1 0 1 0 0 41 1 1 1 1 1 1 0 1 1 1 1 1 1 1 41 0 1 1 1 1 1 0 0 1 1 1 0 1 1 41 1 1 1 1 1 1 0 1 1 1 1 1 1 1 41 0 0 0 0 0 0 0 0 0 0 0 0 0 0 41 0 0 0 0 0 0 0 0 0 0 0 0 1 0 42 1 1 1 1 1 1 0 1 1 1 1 1 1 1 42 0 1 1 1 1 1 0 0 1 1 1 1 1 1 42 1 1 1 1 1 1 0 1 1 1 1 1 1 1 42 1 1 1 1 1 1 0 1 1 1 1 1 1 1 42 0 0 0 0 0 1 0 1 1 1 1 0 0 1 42 0 0 0 0 0 0 0 0 0 0 0 0 1 1

218 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

43 1 0 0 0 0 0 0 1 1 1 1 1 1 1 43 0 0 0 0 0 0 0 0 0 1 1 1 0 0 43 0 0 0 0 0 0 0 0 0 0 1 1 1 0 43 0 0 0 0 0 0 0 0 0 0 1 1 1 1 43 0 0 0 0 0 0 0 0 0 0 1 1 1 1 43 0 0 0 0 0 0 0 0 0 0 1 1 0 0 44 1 1 1 1 1 1 1 1 1 1 1 1 1 1 44 1 1 1 1 1 1 1 1 1 1 1 1 1 1 44 1 1 1 1 1 1 1 1 1 1 1 1 1 1 44 1 1 1 1 1 1 0 1 1 1 1 1 1 1 44 1 1 1 1 1 1 0 1 1 1 1 1 1 1 44 1 1 1 1 1 1 1 1 1 1 1 1 1 1 45 1 1 1 1 1 1 0 0 0 0 0 0 0 0 45 0 0 0 0 0 0 0 0 0 0 0 0 0 0 45 1 1 1 1 1 1 0 0 0 0 0 0 0 0 45 0 0 0 0 0 0 0 0 0 0 0 0 0 0 45 0 0 0 0 0 0 0 0 0 0 0 0 0 0 45 0 0 0 0 0 0 0 0 0 0 0 0 0 0 46 1 1 1 1 1 1 1 0 1 1 1 0 0 0 46 1 1 1 1 1 1 0 1 1 1 1 1 1 1 46 0 0 0 0 1 0 0 0 0 0 1 0 0 1 46 1 1 1 1 1 1 1 1 0 0 1 0 0 1 46 0 0 0 0 0 0 0 0 0 0 0 0 0 0 46 0 0 0 0 0 0 0 0 0 0 0 0 0 0 47 1 1 1 1 1 1 1 1 1 1 1 1 1 1 47 1 1 1 1 1 1 0 1 1 1 1 1 1 1 47 1 1 1 1 1 1 0 1 1 1 1 1 1 1 47 1 0 1 1 1 1 0 1 1 1 1 1 1 1 47 0 1 0 0 0 1 0 0 0 0 1 0 0 0 47 0 0 0 0 0 0 0 0 0 0 0 0 0 0 48 0 0 0 0 0 0 0 0 1 1 1 1 1 1 48 0 0 0 0 0 0 0 0 1 1 1 1 1 1 48 0 0 0 0 0 0 0 0 0 1 1 1 1 1 48 0 0 0 0 0 0 0 0 0 1 1 1 1 1 48 0 0 0 0 0 0 0 0 0 0 0 0 0 0 48 0 0 0 0 0 0 0 0 0 0 0 0 0 0 49 1 1 1 1 1 1 1 1 1 1 1 1 1 1 49 1 1 1 1 1 1 1 1 1 1 1 1 1 1 49 1 1 1 1 1 1 1 1 1 1 1 1 1 1 49 1 1 1 1 1 1 0 1 1 1 1 1 1 1 49 1 1 1 1 1 1 0 1 1 1 1 1 1 1 49 1 1 1 1 1 1 0 1 1 1 1 1 1 1

219 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

50 1 1 1 1 1 1 1 1 1 1 1 1 1 1 50 1 1 1 1 1 1 0 1 1 1 1 1 1 1 50 1 1 1 1 1 1 1 1 1 1 1 1 1 1 50 1 1 1 1 1 1 0 1 1 1 1 1 1 1 50 1 1 1 1 1 1 0 0 0 1 1 1 1 1 50 1 1 1 1 1 1 0 0 0 1 1 1 1 1 51 1 1 1 1 1 1 1 0 1 1 1 1 1 1 51 0 0 0 0 0 0 1 1 0 1 1 1 1 1 51 0 0 0 0 0 0 0 0 0 0 1 0 1 0 51 0 0 0 1 1 1 1 1 1 1 1 1 0 1 51 0 0 0 0 0 0 0 0 0 0 0 0 0 0 51 0 0 0 0 0 0 0 0 0 0 0 0 0 0 52 1 1 1 1 1 1 0 0 1 1 1 1 1 1 52 1 1 1 1 1 1 0 0 0 1 1 1 1 1 52 1 1 1 1 1 1 0 0 0 1 1 1 1 1 52 1 1 1 1 1 1 0 0 0 0 0 0 0 0 52 1 0 0 0 0 0 0 0 0 0 0 0 0 0 52 0 0 0 0 0 0 0 0 0 0 0 0 0 0 53 1 1 1 1 1 1 1 1 1 1 1 1 1 1 53 1 1 1 1 1 1 0 1 1 1 1 1 1 1 53 1 1 1 1 1 1 0 1 1 1 1 1 1 1 53 1 1 1 1 1 1 1 1 1 1 1 1 1 1 53 1 1 1 1 1 1 0 1 1 1 1 1 1 1 53 1 1 1 1 1 1 0 1 1 1 1 1 1 1 54 1 1 1 1 1 1 1 1 1 1 1 0 1 1 54 1 1 1 1 1 1 1 0 0 0 0 0 1 1 54 ...... 54 1 1 1 1 1 1 0 0 1 1 1 1 1 1 54 0 0 0 0 0 0 0 0 0 0 0 0 0 0 54 0 0 0 0 0 0 0 0 0 0 0 0 0 0 55 1 1 1 1 1 1 1 1 1 1 1 1 1 1 55 1 0 0 0 0 0 0 0 0 1 0 0 0 1 55 1 1 1 1 1 1 0 1 1 1 1 1 1 1 55 ...... 55 1 1 1 1 1 1 0 0 0 0 1 1 1 1 55 1 1 1 1 1 1 0 1 0 1 0 1 1 1 56 1 1 1 1 1 1 1 1 1 1 1 1 1 1 56 1 1 1 1 1 1 1 1 1 1 1 1 1 1 56 1 1 1 1 1 1 0 1 1 1 1 1 1 1 56 1 1 1 1 1 1 0 1 1 1 1 1 1 1 56 1 0 1 0 1 1 0 0 0 0 0 0 0 0 56 0 0 1 0 0 1 0 0 0 0 0 0 0 0

220 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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221 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

64 1 1 1 1 1 1 1 1 1 1 1 1 1 1 64 0 1 1 1 1 1 0 1 1 1 1 1 1 1 64 1 0 0 1 0 0 0 0 0 0 0 0 0 0 64 1 1 1 1 1 1 0 1 1 1 1 1 1 1 64 1 1 1 1 1 1 0 1 0 1 1 1 1 1 64 0 0 0 0 0 0 0 0 1 1 0 1 1 1 65 1 1 1 1 1 0 1 0 1 0 0 0 0 0 65 1 1 1 1 1 1 1 1 1 1 1 1 1 1 65 1 1 0 0 1 0 1 1 1 1 0 1 1 0 65 1 1 1 1 1 1 0 1 1 1 1 1 1 0 65 1 1 1 1 1 1 0 1 1 1 1 1 1 1 65 1 1 1 1 1 1 0 0 0 0 0 0 0 0 66 1 1 1 1 1 1 1 1 1 1 1 1 1 1 66 1 1 1 1 1 1 1 1 1 1 1 1 1 1 66 1 1 1 1 1 1 1 1 1 1 1 1 1 1 66 1 1 1 1 1 1 1 1 1 1 1 1 1 1 66 1 1 1 1 1 1 0 1 1 1 1 1 1 1 66 1 1 0 0 0 1 0 0 1 1 1 1 1 1 67 1 1 1 1 1 1 0 0 0 1 1 1 1 1 67 1 1 0 1 1 1 0 0 0 1 1 1 1 1 67 1 1 1 1 1 1 0 0 0 1 1 1 1 1 67 1 1 1 1 1 1 0 0 0 1 1 1 1 1 67 0 0 0 0 0 0 0 0 0 0 0 0 0 0 67 1 1 1 1 1 1 0 0 0 0 0 0 0 0 68 1 1 1 1 1 1 1 1 1 1 1 1 1 1 68 1 0 0 0 0 0 1 1 1 1 1 1 1 1 68 0 0 0 0 0 1 1 1 1 1 0 1 0 0 68 1 1 1 1 1 1 1 1 1 1 0 1 1 1 68 0 0 0 0 0 0 0 1 0 0 0 0 0 1 68 0 0 0 0 0 0 0 0 0 0 0 0 0 0 69 1 1 1 1 1 1 1 1 1 1 1 1 1 1 69 1 1 1 1 1 1 0 0 1 1 1 1 1 1 69 1 1 1 1 1 1 0 0 1 1 1 1 1 1 69 1 1 1 1 1 1 0 0 0 1 1 1 1 1 69 0 0 0 0 0 0 0 0 0 1 1 0 0 0 69 0 0 0 0 0 0 0 0 0 0 0 0 0 0 70 1 0 0 0 0 0 0 0 0 0 0 0 0 0 70 1 0 1 0 0 0 0 0 0 0 1 1 0 0 70 0 0 0 0 0 0 0 0 0 1 0 0 0 1 70 0 0 0 0 0 0 0 1 1 1 1 1 1 1 70 0 0 0 0 0 0 0 0 1 1 1 1 1 1 70 0 0 0 0 0 0 0 0 0 0 0 0 0 0

222 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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223 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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224 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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225 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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226 SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/

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227 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

1 1 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 1 0 0 0 1 0 0 0 0 0 0 1 1 0 0 0 0 0 1 0 0 0 0 0 0 2 0 1 1 1 1 1 2 1 1 1 0 1 1 2 1 1 1 1 1 1 2 1 1 0 1 1 1 2 0 1 0 1 0 0 2 0 0 0 0 0 0 3 1 1 1 0 1 1 3 0 1 1 0 0 0 3 0 0 0 0 0 0 3 0 0 0 0 0 0 3 0 0 0 0 0 0 3 0 0 0 0 0 0 4 1 1 1 1 1 1 4 1 1 1 1 1 1 4 1 1 1 1 1 1 4 1 1 1 1 1 1 4 1 1 1 1 1 1 4 0 1 0 0 0 0 5 0 0 0 1 0 1 5 1 1 1 1 1 1 5 ...... 5 1 1 1 1 1 1 5 1 1 1 1 1 1 5 0 1 1 0 0 0 6 1 1 1 1 1 1 6 1 1 1 1 1 1 6 1 1 1 1 1 1 6 1 1 1 1 1 1 6 1 1 1 1 1 1 6 0 0 0 0 0 0 7 0 0 0 0 0 0 7 0 0 0 0 0 0 7 0 0 0 0 0 0 7 0 0 0 0 0 0 7 0 0 0 0 0 0 7 0 0 0 0 0 0

228 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

8 1 1 1 1 1 1 8 1 1 1 1 1 1 8 1 1 1 1 1 1 8 1 1 1 1 1 1 8 0 0 0 0 0 0 8 0 0 0 0 0 0 9 0 0 1 0 0 0 9 1 1 1 1 1 1 9 0 0 0 0 0 0 9 1 1 1 1 1 1 9 0 0 0 0 0 0 9 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 11 1 1 1 1 1 1 11 0 0 0 0 0 0 11 1 1 1 1 1 1 11 1 1 1 1 1 1 11 1 1 1 1 1 1 11 1 0 1 1 1 1 12 1 1 1 1 1 1 12 1 1 1 1 1 1 12 1 1 1 1 1 1 12 1 1 1 1 1 1 12 0 0 0 0 0 0 12 0 0 0 0 0 0 13 1 0 0 0 0 0 13 0 0 0 0 0 1 13 0 0 0 0 0 0 13 0 0 0 0 0 0 13 0 0 0 1 1 1 13 0 0 0 0 0 0 14 0 0 1 0 1 1 14 0 1 1 1 0 1 14 1 1 1 1 1 1 14 ...... 14 0 0 0 0 0 0 14 0 0 0 0 0 0

229 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

15 1 1 1 1 1 1 15 0 1 0 0 1 0 15 1 1 1 1 1 0 15 1 1 1 1 1 1 15 0 0 0 0 0 1 15 0 0 0 0 0 0 16 1 1 1 1 1 1 16 1 1 1 1 1 1 16 1 1 1 1 1 1 16 1 1 1 1 1 1 16 1 1 1 1 1 1 16 0 0 0 0 0 0 17 1 0 0 0 0 0 17 0 0 0 0 0 0 17 0 0 0 0 0 0 17 0 0 0 0 0 0 17 0 0 0 0 0 0 17 0 0 0 0 0 0 18 1 1 1 1 1 0 18 0 0 0 1 1 0 18 0 0 0 0 0 0 18 1 1 1 0 0 1 18 0 0 0 0 0 0 18 0 0 0 0 0 0 19 1 0 1 1 1 1 19 0 0 0 0 0 0 19 0 0 0 0 0 1 19 1 1 1 1 1 1 19 0 0 0 0 1 1 19 0 0 0 0 0 0 20 1 1 1 1 1 1 20 1 1 1 1 1 1 20 1 1 1 1 1 1 20 1 1 1 1 1 1 20 1 1 1 1 1 1 20 0 0 0 1 0 0 21 0 0 0 0 0 0 21 0 0 0 0 0 0 21 1 1 1 1 1 1 21 ...... 21 1 1 1 1 1 1 21 1 1 1 1 1 1

230 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

22 1 1 1 1 1 1 22 0 0 0 0 0 0 22 0 1 1 1 1 0 22 0 0 0 0 0 0 22 0 0 0 0 0 0 22 0 0 0 0 0 0 23 1 1 1 1 1 1 23 1 1 1 1 1 0 23 1 0 1 1 1 1 23 1 1 1 1 1 0 23 0 0 0 0 0 0 23 0 0 0 0 0 0 24 0 0 0 0 0 0 24 0 0 0 0 1 0 24 0 0 0 0 0 0 24 1 1 1 1 1 1 24 1 1 1 1 1 1 24 0 0 0 0 0 0 25 1 1 1 1 1 1 25 1 1 1 1 1 1 25 1 1 1 1 1 1 25 0 1 0 0 1 1 25 0 0 0 0 0 0 25 1 1 0 1 0 0 26 1 0 1 1 1 1 26 1 1 1 1 1 1 26 1 1 1 1 1 1 26 1 1 1 1 1 1 26 1 1 1 1 1 1 26 1 1 1 1 1 1 27 1 0 1 1 0 0 27 0 0 0 0 0 0 27 0 0 0 0 0 1 27 1 1 1 1 1 1 27 1 1 1 1 1 1 27 0 0 0 0 0 0 28 1 1 1 1 1 1 28 1 1 1 1 1 1 28 1 1 1 1 1 1 28 1 1 1 1 1 1 28 1 1 1 0 1 0 28 0 0 0 0 0 0

231 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

29 1 1 1 1 1 1 29 0 0 0 0 0 0 29 1 1 1 1 1 1 29 1 1 1 0 0 1 29 1 1 1 1 1 1 29 0 0 0 0 0 0 30 1 1 1 1 1 1 30 1 1 1 1 1 1 30 ...... 30 1 1 1 1 1 1 30 0 0 0 0 0 0 30 0 0 0 0 0 0 31 0 0 0 0 0 0 31 0 0 0 0 0 0 31 ...... 31 1 1 1 1 1 1 31 1 0 1 0 1 0 31 0 0 0 0 0 0 32 1 1 1 1 0 0 32 0 0 0 0 0 0 32 0 0 0 0 0 0 32 0 0 0 0 0 0 32 0 0 0 0 0 0 32 0 0 0 0 0 0 33 1 1 1 1 1 1 33 1 1 1 1 1 1 33 1 1 1 1 1 1 33 1 1 1 1 1 1 33 1 1 1 1 1 1 33 0 0 0 0 0 0 34 1 1 1 1 1 1 34 1 1 1 1 1 1 34 1 1 1 1 1 1 34 1 1 1 1 1 1 34 0 0 0 0 0 0 34 0 0 0 1 0 1 35 0 0 0 0 0 0 35 0 0 0 0 0 1 35 0 0 0 0 1 0 35 0 0 0 0 0 0 35 0 0 0 0 0 0 35 0 0 0 0 0 0

232 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

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233 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

43 1 1 1 0 0 0 43 0 0 0 0 0 0 43 0 0 0 0 0 0 43 0 1 1 0 1 0 43 0 0 0 0 0 0 43 1 1 0 0 0 0 44 1 1 1 1 1 1 44 1 1 1 1 1 1 44 1 1 1 1 1 1 44 1 1 1 1 1 1 44 1 1 1 1 1 1 44 1 1 1 1 1 1 45 0 0 0 0 0 0 45 0 0 0 0 0 0 45 0 0 0 0 0 0 45 0 0 0 0 0 0 45 0 0 0 0 0 0 45 0 0 0 0 0 0 46 0 1 0 1 0 1 46 1 0 0 0 0 1 46 0 0 0 0 0 1 46 1 0 0 0 0 1 46 0 0 0 0 0 0 46 0 0 0 0 0 0 47 1 1 1 1 1 1 47 1 1 1 1 1 1 47 1 1 1 1 1 1 47 1 1 1 1 1 1 47 0 0 0 0 0 0 47 0 0 0 0 0 0 48 1 1 1 1 1 1 48 1 1 1 1 1 1 48 1 0 0 0 0 0 48 1 1 1 1 1 1 48 0 0 0 0 0 0 48 0 0 0 0 0 0 49 1 1 1 1 1 1 49 1 1 1 1 1 1 49 1 1 1 1 1 1 49 1 1 1 1 1 1 49 1 1 1 1 1 1 49 1 1 1 1 1 1

234 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

50 1 1 1 1 1 1 50 1 1 1 1 1 1 50 1 1 1 1 1 1 50 1 1 1 1 1 1 50 1 1 1 1 1 1 50 1 1 1 1 1 1 51 1 1 1 1 1 1 51 1 0 0 0 1 1 51 1 0 1 0 0 0 51 1 1 1 1 1 1 51 0 0 0 0 0 0 51 0 0 0 0 0 0 52 1 1 1 1 1 1 52 1 1 1 1 1 1 52 1 1 1 1 1 1 52 0 0 0 0 1 1 52 0 0 0 0 0 0 52 0 0 0 0 0 0 53 1 1 1 1 1 1 53 1 1 1 1 1 1 53 1 1 1 1 1 1 53 1 1 1 1 1 1 53 1 1 1 1 1 1 53 1 1 1 1 1 1 54 1 1 1 1 0 1 54 0 0 0 0 0 0 54 ...... 54 1 1 1 1 1 1 54 0 0 0 0 0 0 54 0 0 0 0 0 0 55 1 1 1 1 1 1 55 0 0 0 0 0 0 55 1 1 1 1 1 1 55 ...... 55 0 1 1 1 0 0 55 0 1 0 0 0 0 56 1 1 1 1 1 1 56 1 1 1 1 1 1 56 1 1 1 1 1 1 56 1 1 1 1 1 1 56 0 0 0 0 0 0 56 0 0 0 0 0 0

235 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

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236 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

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237 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

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238 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

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239 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

85 1 1 1 1 1 1 85 1 1 1 1 1 1 85 ...... 85 1 1 1 1 1 0 85 0 0 0 0 0 0 85 0 0 0 0 0 0 86 1 1 1 1 1 1 86 1 1 1 1 1 1 86 1 1 1 1 1 1 86 1 1 1 1 1 1 86 0 0 0 0 0 0 86 1 1 1 1 1 1 87 1 1 1 1 1 1 87 0 0 0 0 0 1 87 1 1 1 1 1 1 87 1 0 0 1 1 1 87 1 0 1 1 1 0 87 0 0 0 0 0 0 88 0 0 0 1 0 1 88 1 1 1 1 0 1 88 1 1 1 1 1 1 88 1 1 1 1 1 1 88 0 0 0 0 0 0 88 0 0 0 0 0 0 89 1 0 0 0 0 0 89 0 0 0 0 0 0 89 0 0 1 1 1 1 89 0 0 0 1 1 0 89 0 0 0 0 0 0 89 0 0 0 0 0 0 90 1 1 1 1 1 1 90 0 0 0 0 0 0 90 0 0 1 1 1 1 90 1 1 1 1 1 1 90 1 1 1 1 1 1 90 0 0 1 0 0 1 91 1 1 0 0 1 1 91 0 0 0 0 0 0 91 1 0 0 0 1 1 91 0 0 0 0 0 1 91 0 0 0 0 0 0 91 0 0 0 0 0 0

240 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

92 1 1 1 1 1 1 92 1 1 1 1 1 1 92 1 1 1 1 1 1 92 1 1 1 1 1 1 92 1 1 1 1 1 1 92 0 0 0 0 0 0 93 0 1 1 1 1 1 93 1 1 1 1 1 1 93 1 1 1 1 1 1 93 1 1 1 1 1 1 93 1 1 1 1 1 1 93 0 0 0 0 0 1 94 1 1 0 1 0 0 94 1 1 1 1 1 1 94 0 0 0 0 1 1 94 1 1 1 1 1 1 94 0 0 0 0 0 0 94 0 0 0 0 0 0 95 0 0 0 0 0 0 95 0 1 0 0 0 0 95 1 1 0 1 1 1 95 1 1 1 1 1 1 95 0 0 0 0 0 0 95 0 0 0 0 0 0 96 0 1 1 0 0 1 96 0 0 0 0 0 1 96 ...... 96 1 1 1 1 1 1 96 0 0 0 0 0 1 96 0 0 0 0 0 0 97 0 1 1 0 1 1 97 0 0 0 0 0 0 97 0 1 0 0 0 1 97 0 0 1 1 0 0 97 1 1 1 1 1 1 97 0 0 0 0 0 0 98 1 1 1 1 1 1 98 1 1 1 0 0 0 98 ...... 98 1 1 1 1 1 1 98 0 0 0 0 0 0 98 0 0 0 0 0 0

241 SUB CT37 CT41 CT45 CT49 CT53 CT57 # 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80

99 1 1 1 1 1 1 99 0 1 1 0 0 0 99 1 1 0 0 0 0 99 0 1 1 0 0 0 99 0 0 0 0 0 0 99 0 0 1 0 0 0 100 1 1 1 1 1 1 100 1 1 1 1 1 1 100 1 1 1 1 1 1 100 1 1 1 1 1 1 100 1 1 1 1 1 1 100 0 0 0 0 0 0

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