Intentional Versus Unintentional Child Toxicity at National Center of Environmental and Clinical Research of Toxicology (Nectr)

INTENTIONAL VERSUS UNINTENTIONAL CHILD TOXICITY AT NATIONAL CENTER OF ENVIRONMENTAL AND CLINICAL RESEARCH OF TOXICOLOGY (NECTR)

Thesis

Submitted for partial fulfillment of Master Degree (M.Sc.) in FORENSIC MEDICINE & CLINICAL TOXICOLOGY

By RANIA MOHSEN ABDEL RAHEEM (M.B., B.CH.) Demonstrator of Forensic Medicine and Clinical Toxicology Faculty of Medicine, Cairo University

Under Supervision of

PROF. DR. DINA ALI SHOKRY Professor and Head of Forensic Medicine & Clinical Toxicology Department Faculty of Medicine – Cairo University

PROF. DR. HODA ABD ELMAGIED EL GHAMRY Professor of Forensic Medicine & Clinical Toxicology Faculty of Medicine – Cairo University

DR. MARWA ISSAK MOHAMED Lecturer of Forensic Medicine & Clinical Toxicology Faculty of Medicine – Cairo University

Faculty of Medicine Cairo University 2018

ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﻴﻢ

ACKNOWLEDGEMENT

First and foremost, all praises to ALLAH, who gave me the strength to accomplish this achievement and gifted me with people who tried to help all-through.

It is a great honor to me to express my deepest gratitude to Prof. Dr. Dina Ali Shokry, Professor and Head of Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Cairo University, for her unlimited support, valuable guidance and sincere supervision that were the most driving forces in the initiation and progress of this work. She performed much effort and consumed much of her time in guiding me through this thesis.

No words can fulfill my infinite thanks and appreciation to Prof. Dr. Hoda Abd Elmagied El Ghamry, Professor of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, for her continuous encouragement, meticulous supervision and great-unlimited help through this work.

I wish to express my deepest thanks to Dr. Marwa Isshk Mohamed, Assistant Lecturer of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, for her great support, precious advices, and valuable guidance.

Also I am deeply grateful to my professors and my colleagues in the Department of Forensic Medicine & Clinical Toxicology, Faculty of Medicine - Cairo University for their help and support.

III

DEDICATION

Dedication

To my father who taught me the meaning of responsibility To my mother who believed in me and taught me to trust in Allah and believe in hard working. I owe her everything To my husband, my daughters and my brothers for their endless love, care, and support and for being always by my side

CONTENTS

PAGE

ABSTRACT …………………………………………...……….… VII

LIST OF TABLES ……………………………………………..... VIII

LIST OF FIGURES …………………………………..……………. X

LIST OF ABBREVIATIONS ……………………….………..… XII

INTRODUCTION …………………………………………………. 1

AIM OF THE WORK ……….……………………………………... 3

REVIEW OF LITERATURE .……………………………………... 4

o Chapter 1: Pediatric Toxicokinetics and Toxicodynamics …….. 4 Toxicokinetics (absorption) ………………..………………………… 4 Distribution …………………………..……………………….…….. 8 Metabolism (bio-transformation) ….………..………………….. 11 Excretion …………………………………………………………... 16 Toxicodynamics …………………………….……………………... 18

o Chapter 2: Common Poisons in Pediatric Toxicity ……………… 21 Household products ……….……….…………………………….. 21 Corrosives ………………………….…….………………………... 21 Kerosene …………..……………………..……………………….. .25 Pesticides ……………………………..…………………………… 28 Organophosphorus ………………………………………….. .… 29 Carbamates …………………………………………….…… ……34 Drug of abuse (cannabis) ……………………….…………..…. 36 Tramadol ………………………………………………...……….. 38 Medications ……………………………………………………... 43 Paracetamol ………….………………………………… …….... 43 Theophylline ……………….………….……………………….... 48

o Chapter 3: Manner of Pediatric Toxicity and Other Medicolegal Aspects ……………………………….…………………………. 52 Unintentional child toxicity …………………………… ………… 52 Intentional (suicidal toxicity )……………..…………..…………… 53 Intentional (homicidal toxicity )..……………………..……….….. 54 Important medicolegal concept …………………………………... 55 Medical aspect ….…………………………….……………….……… 55 Legal aspect ……………………….………….………..……….…….. 63

CONTENTS

SUBJECTS AND METHODS …..……………………………… 65

RESULTS …………………………………………………………. 71

DISCUSSION …………………………………...…………..…... 131

CONCLUSION & RECOMMENDATIONS …………………. 156

SUMMARY …………………………………………………… 161

REFERENCES ……………………………………………….. 168

APPENDICES …………………………………………………. 195

ARABIC Summary …………………………………………… 1-7

ABSTRACT

Background: Poisoning is an important emergency as well as major problem in pediatric age groups throughout the world. Most of the poisoning in children is accidental. Unfortunately, the incidence of deliberate poisoning among adolescents is increasing due to changing familial and social conditions in our society. The causes and types of poisoning vary in different parts of the world and within the country also depending upon factors such as education, demography, socioeconomic factors, customs and local belief.

Aim of the work: The purpose of this study was to Identify the common manner of toxicity and rate of child toxicity in Egypt. Also, it aimed to elucidate the precipitating factors for child poisoning and the common complication.

Subjects and Methods: The current study was conducted on 152 of Egyptian participant of both sexes in age blew 18 years old at NECTR; 96 females and 56 males. They were classified into 4 age groups; toddlers (1-<3 yrs), early childhood (3-<9 yrs), late childhood (9-<13 yrs) and adolescent (13-<18 yrs). Data were analyzed with respect to demographic data of the patients: age, sex, residence, level of education and family status, and data of toxicity: manner of toxicity, type of poison, its availability to the child, place of exposure, amount and form of poison, duration between exposure and presentation, the first aid that may be done to the patient, associated morbidity, history of medications and Severity and mortality rate of each poisons detected by poison severity scoring (PSS) and the acute physiology and chronic health evaluation (APACHE II).

Results: Accidental toxicity (58.6%) is still common than intentional toxicity (41.4%), toddlers and males were the most common age group in accidental, while negligence was the most probable cause of accidental toxicity. On other hand adolescent and females were common age group in suicidal, while family problems were the most probable cause of suicidal toxicity. There were multiple significant relations between demographic data (age, sex, residence, level of education and family status) and type of poison, its availability, location of exposure, most probable cause of exposure, manner of toxicity. There were significant relations between PSS and type and amount of poison, vital signs and CNS manifestations, period of admission and hours of delay. There were significant relations and positive correlation between APACHE II and type and amount of poison, vital signs and CNS manifestations, period of admission and hours of delay.

Conclusion and Recommendations: The present study proved that accidental toxicity is still common manner among pediatric age group but there is increasing in incidence of suicidal toxicity among them. Further attention from parent is needed and proper care to children in different age group to prevent and reduce the toxicity in pediatric age group.

Keywords: Pediatric toxicity, Manner of toxicity, Probable cause, Poison severity scoring and APACHE II.

VII

LIST OF TABLES

No. TITLE PAGE 1 Factors affecting absorption in neonates and infants 7 2 Age-related changes in body composition. 11 3 Household agents classified according to their chemical natures 21 4 Grading system for corrosive burns of the alimentary tract with 23 endoscopy. 5 Major pesticide classes and selected examples 28 6 Clinical Stages of Acetaminophen Toxicity 46 7 Indications for hemodialysis/hemoperfusion With Theophylline 51 8 methods used to analysis different poisons in different samples 56 9 ACHE II scoring system according to acute physiology and chronic 67 health diseases. 10 Poison scoring system (PSS) according to signs and symptoms 68 11 Distribution of cases according to age and manner of toxicity. 73 12 Relation between age in group 1 and type of poison and its amount. 74 13 Relation between age in group 2 and type of poison and its amount 75 14 Relation between age in group 1 and availability of poison. 76 15 Relation between age in group 2 and availability of poison. 77 16 Relation between age in group 1 and the most probable cause. 78 17 Relation between age in group 2 and the most probable cause. 78 18 Relation between age in group 1 and (location of exposure and 79 previous attempts). 19 Relation between age in group 2 and (location of exposure and 79 previous attempts). 20 Relation between sex and (type of poison and its amount). 81 21 Relation between sex and most probable cause. 82 22 Relation between sex and previous attempts 82 23 Relation between residence and type of poison. 84 24 Relation between residence and 1st aid. 84 25 Relation between residence and availability of poison. 85 26 Relation between residence and the most probable cause of toxicity. 86 27 Relation between residence and hours of delay. 86

VII

LIST OF TABLES

No. TITLE PAGE 28 Relation between educational level and type of poison. 89 29 Relation between educational level and amount of poison. 90 30 Relation between educational level and the most probable cause of 91 toxicity. 31 Relation between mother work and education and the availability of 95 poison 32 Relation father work and education and (previous attempts) 97 33 Relation mother work and education and (previous attempts) 98 34 Relation father work and education and (most probable cause of 100 toxicity) 35 Relation mother work and education and (most probable cause of 101 toxicity). 36 Relation between father work and education and (hours of delay). 102 37 Relation between mother work and education and (hours of delay). 103 38 availability of poisons. 104 39 Relation between type of poison and its availability. 106 40 Relation between type of poison and vital signs 107 41 Relation between amount of poison and vital signs. 107 42 Relation between type of poison and CNS manifestation. 108 43 Relation between amount of poison and CNS manifestation. 109 44 Relation between type of poison and specific antidote 110 45 Relation between type of poison and admission. 111 46 Relation between amount of poison and admission. 111 47 Relation between type of poison and outcome. 112 48 Relation between type of poison and period of admission. 113 49 Relation between amount of poison and period of admission. 114 50 Relation between hrs. of delay and decontamination treatment. 115 51 Correlation coefficient between hrs of delay and period of admission 115 52 Relation between 1st aid and outcome. 116 53 Relation between vital signs and outcome. 118 54 Relation between CNS manifestation and outcome 118 55 Relation between vital signs and period of admission. 119 56 Relation between CNS manifestation and period of admission. 119

VIII

LIST OF TABLES

No. TITLE PAGE 57 Relation between main type of poison and PSS. 120 58 Relation between main type of poison and APACHE II. 121 59 Relation between amount of poison and PSS. 122 60 Relation between amount of poison and APACHE II. 122 61 Relation between history of previous disease and APACHE II. 123 62 Relation between vital signs and PSS. 124 63 Relation between vital signs and APACHE II. 125 64 Relation between CNS manifestation and PSS. 126 65 Relation between CNS manifestation and APACHE II. 126 66 Correlation between period of admission and APACHE II. 127 67 Relation between period of admission and PSS. 128 68 Relation between outcome and APACHE II. 129 69 Relation between outcome and PSS. 130

LIST OF FIGURES

NO. TITLE PAGE 1 Mechanism of action of corrosive and how causing tissue 22 destruction 2 Pesticide accumulation in synaptic cleft (1), AChE inhibition by 30 pesticide (2), and constant activation of AChR (3) 3 Algorithm of OP poisoning effects 32 4 Mechanism of action of cannabis 36 5 The common medications involved in child toxicity. 43 6 Mechanism of paracetamol action and toxicity 45 7 Action of theophylline 49 8 Distribution of the cases in the present study according to manner 71 of toxicity 9 Distribution according to admission. 71 10 Management of cases. 72 11 Distribution of cases according to final outcome. 72 12 Pie chart showing case distribution according to age. 73 13 Pie chart showing case distribution according to sex. 80 14 Bar chart show distribution of cases according to sex and manner 80 of toxicity. 15 Pie chart showing case distribution according to residence. 83 16 Relation between residence and manner of toxicity 83 17 Distribution of the cases according to their educational level. 87 18 Distribution of cases according to manner of toxicity and their 87 educational level. 19 Distribution of the cases according to father work and education. 92 20 Distribution of the cases according to mother work and education. 92 21 Distribution of cases according to father work and education and 93 manner of toxicity 22 Distribution of cases according to mother work and education and 93 manner of toxicity. 23 Correlation between father work and education and (hours of 102 delay).

LIST OF FIGURES

NO. TITLE PAGE 24 Correlation between mother work and education and (hours of 103 delay). 25 Distribution of the cases according to common type of poison. 104 26 Distribution of the cases according to amount of poison. 105 27 Distribution of the cases according to manner of toxicity and 105 common type of poison. 28 Correlation coefficient between type of poison and period of 113 admission. 29 Correlation coefficient between amount of poison and period of 114 admission. 30 Pie chart shows percentage distribution of cases according to 116 1st aid 31 Pie chart percentage distribution of cases according to vital signs 117 32 Bar chart shows percentage of CNS manifestation of cases 117 33 Correlation between main type of poison and APACHE II. 121 34 Correlation between amount of poison and APACHE II. 123 35 Correlation between history of previous disease and APACHE II. 124 36 Correlation between vital signs and APACHE II. 125 37 Correlation between CNS manifestation and APACHE II. 127 38 Correlation between period of admission and PSS. 128 39 Correlation between outcome and APACHE II. 129

LIST OF ABBREVIATIONS

List of Abbreviations

Abbreviation Full name ∆9-THC ∆9-Tetrahydrocannabinol

AAG Α1-Acid glycoprotein AChR Acetylcholine receptors ADHD Attention-Deficit/Hyperactivity Disorder ADME Absorption, Distribution, Metabolism, and Elimination ALT Alanine Amino Transferase APAP N-Acetyl-Para-Aminophenol AST Aspartate Amino transferase BBB Blood-Brain Barrier BSA Body Surface Area BW Body Weight CB Cannabinoid receptors CBC Complete Blood Count CFC Cerebrospinal Fluid Concentrations ChE Cholinesterase CK Creatinine Kinase CNS Central Nervous System CO Carbon Mono oxide Cr Creatinine CYP3A4 Cytochrome P450 3A4 CYPs Cytochromes P450 DIC Disseminated Intravascular Coagulopathy ECG Electrocardiogram EMIT Enzyme-multiplied immunoassay technique FMOs Flavin-containing monooxygenases GABA Gama Amino Butric acid GC Gas Chromatography GC/MS Gas Chromatography/Mass Spectrometry, GC-MS Gas Chromatography–Mass Spectrometry GF Glomerular Filtration

XII

LIST OF ABBREVIATIONS

Abbreviation Full name GFR Glomerular Filtration Rate GSH Glutathione GST Glutathione S-Transferases HCN Hydrogen Cyanide HPLC High-Pressure liquid Chromatography Hrs Hours HSA Human Serum Albumin INR International Normalized Ratio LC liquid Chromatography MS Mass Spectrometric MSBP Munchausen syndrome by proxy NAPQI N-Acetyl-P-benzoquinoneimine NATs N-Acetyltransferases NSAIDs Non steroidal anti-inflammatory drugs NTE Neuropathy Target Esterase OP Organophosphorus PD Pharmacodynamic P-gp P-glycoprotein PGs Prostaglandins p-value Probability value RIA Radioimmunoassay SS Serotonin syndrome STs Sulphotransferases TD Toxicodynamics TK Toxicokinetics TLC Thin-layer Chromatography UGTs Uridine 50-diphospho-GlucuronosylTransferases WHO World Health Organization yr Years

XIII

INTRODUCTION

Poisoning is an important emergency as well as major problem in pediatric age groups throughout the world. The causes and types of poisoning vary in different parts of the world and within the country also depending upon factors such as education, demography, socioeconomic factors, customs and local belief (Narayan, 2008). WHO estimated that near 45000 children die from poisoning every year (Zarezadeh & Bahrampour, 2011).

The mortality and morbidity due to poisoning is preventable in children. Poisoning is the fourth leading cause of unintentional injury following road traffic accident, burns and drowning (Hyder et al., 2008).

As toxicokinetics (TK) and toxicodynamics in children are different than in adults due to the continuous growth in children’s different systems, their physical activity, and their body weight (Saadeh & Klaunig, 2014). In some cases, stage of development can alter the action of, and response to a drug that is a truly age-dependent difference in pharmacodynamics. This may be true of both the desired action and adverse events (Stephenson, 2005).

Each year, huge number of patients under 6 years come to the emergency department with history of poisoning (Devaranavadagi et al., 2017 ). Almost always accidental poisoning in children occurs under 5 year of age (Alazab, 2012). In older children and adolescents, suicide attempts are more common (Andiran, 2004). Poisoning may result from pica, thirst or hunger. It may be a manifestation of insecurity, self-injury due to guilty feelings or attention seeking behavior (Devaranavadagi et al., 2017 ).

Accidental poisoning remains the most common in children (Alije Keka et al., 2014) but in the last decades suicide had increased in children and represents the third leading cause of death (Olguin et al., 2011).

INTRODUCTION

The severity of poisoning depends on the nature of the ingested drug, its amount and the quality of medical care (McGregor et al., 2009). The most common agents involved in poisoning are over-the-counter (OTC) medication, prescription medication, household products, pesticides, kerosens and poisonous plants (Lam, 2003). At 2-3 years of age, house cleaning products cause most common cases of poisoning, at 3-5 years of age, the medications kept in cupboard or left open are the main causes of poisoning. Whereas, at school age and during adolescence, medication used for committing suicide are the main cause of poisoning (Mutlu, 2010).

Adolescents live stressful period during puberty as there are many physiological and emotional changes occur that make them more reliable to affect with minor events such as poor school performance, bulling in school, failed relationship, conflict with parents, drug abuse, emotional insecurity and associated psychological conditions (Aggarwal et al., 2014). All these factors lead to increase suicidal attempts among older children and adolescents.

AIM OF THE WORK

The aim of this study was to identify the common manner of toxicity and rate of child toxicity in Egypt. Also, it aimed to elucidate the precipitating factors for child poisoning and the common complication.

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

PEDIATRIC TOXICOKINETICS AND TOXICODYNAMICS

Poisoning is when cells are injured or destroyed by the inhalation, ingestion, injection or absorption of a toxic substance. Key factors that predict the severity and outcome of poisoning are the nature, dose, formulation and route of exposure of the poison; co-exposure to other poisons; patterns change according to age group, type of exposure and state of nutrition of the child or (fasting status); age and preexisting health conditions. Poisons are substances which produce ill health or death by chemical reaction or other activity on the molecular scale. Children being vulnerable section of our society, have been almost the principal victims of all the social ills, poisoning being no exception (Manikyamba et al., 2015).

Toxicokinetics and toxicodynamics determine the effects of toxins. Toxicokinetics (what the body does to the xenobiotic) is defined as the quantitative study of drug absorption, distribution, metabolism, and elimination (ADME). Toxicodynamics is clinically more elusive and difficult to precisely quantify. It is the study of the biochemical and physiological effects of drugs in the body. Thus, toxicodynamics can be thought of as “what the drug does to the body.” Despite being 2 distinct entities, there is substantial interplay between toxicokinetics and the resultant toxicodynamics (Sandritter et al., 2017).

TOXICOKINATICS

Toxicokinetics (TK) in children is different than in adults due to the continuous growth in children’s respiratory system, their physical activity, and their body weight (Saadeh & Klaunig, 2014). For example, the exposure to an ultra fine particulate matter of air pollutant can be two to four times higher in a three-month old child than in an adult, as a result of lung deposition and body size factors (Ginsberg et al., 2005). The xenobiotic must

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics first enter the body (e.g., ingestion, dermal, rectal, submucosal) and be absorbed into the bloodstream. Once in the bloodstream, the toxin can be distributed, ultimately reaching the site in the body where it may produce the desired effect at a receptor or drug target. After the drug-receptor interaction, the xenobiotic returns to the bloodstream and is taken to the liver, where it can be metabolized to substances that are more easily eliminated in the urine or feces (Alcorn & McNamara, 2002).

I. Absorption: Absorption is the process by which axenobiotic enters the bloodstream or another body compartment from the site of administration. The process is characterized by 2 important parameters, the rate and the extent of xenobiotic absorption. The former affects the onset of action of the xenobiotics, and the latter essentially controls the dose (Lu et al., 2014). Xenobiotics administered via the intravenous route are considered to be 100% bioavailable, meaning that the entire xenobiotic dose has reached the circulation. Routes that require absorption include oral, intramuscular, subcutaneous, and topical/transdermal and can result in adverse effects if given in sufficient quantities. Drug absorption plays a pivotal role in determining pharmacodynamic responses (Matalová et al., 2016).

For a xenobiotic to be absorbed into the circulation, the active form must first be liberated from the dosage form. Liberation depends on physiochemical factors of the xenobiotic, the dosage form, and the environment at the site of administration. There are multiple mechanisms by which xenobiotic are absorbed into the circulation, including passive diffusion, convective transport, active transport, facilitated transport, ion pair transport, and pinocytosis∗ (Sumpter et al., 2009). Passive diffusion is one of the most important mechanisms of xenobiotic absorption; however, active transporters such as P-glycoprotein (P-gp) can be particularly important

∗Pinocytosis is the ingestion of liquid into a cell by the budding of small vesicles from the cell membrane (Holley, 2017).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics owing to drug-drug and drug-food interactions. P-glycoprotein is a transporter located in the endothelium of multiple organs, including the gastrointestinal tract lumen and the blood- brain barrier. This efflux transporter is responsible for pumping drugs back into the gut lumen and decreasing bioavailability. Digoxin is an example of a drug that is transported by P-gp (Sandritter et al., 2017).

There are many differences occur in this process in different ages affecting the action of xenobiotic (Table 1). For example, In the gastrointestinal tract, several age-related anatomic and physiological changes have been found to influence drug absorption. Gastric pH is neutral at birth but falls to pH 1-3 within 24 to 48 hours after birth. The pH then gradually returns to neutral again by day 8 and subsequently declines very slowly, reaching adult values only after 2 years of age. This higher pH in neonates and young infants may have a protective effect on acid-labile drugs and may at least partially account for the higher bioavailability of beta-lactam antibiotics. The bioavailability of orally administered weak acids, such as acetaminophen and phenobarbital, may be reduced in infants and young children due to increased ionization under achlorhydric conditions (Lu et al., 2014).

Gastric emptying and intestinal motility are important determinants for the rate of toxin absorption in the small intestine, the major site of toxin absorption. Gastric emptying time during the neonatal period is prolonged relative to that of the adult. This may partially account for delayed absorption for orally administered phenobarbital, digoxin, and sulfonamides).Other factors such as reduced intestinal absorption surface area and shorter gut transit time may also be responsible for the delayed absorption observed in infant. The age-dependent changes in biliary function and activities of pancreatic enzymes can compromise the body’s ability to solubilize and subsequently absorb some lipophilic drugs (Mahmood, 2016).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Developmental changes in the activity of intestinal toxin-metabolizing enzymes and transporters could potentially alter the bioavailability of toxin. As in preterm infant, an intestinal cytochrome P450 3A4 (CYP3A4) enzyme system is still immature this decrease oral clearance of some drugs as midazolam, which results in decreased presystemic intestinal metabolism and an increased bioavailability (de Wildt et al., 2002). In young children (1-3 years old) had a 77% higher busulfan glutathione conjugation rate compared to the adult, this may lead to an enhanced first-pass intestinal metabolism and a reduced absorption fraction (F) in young children (Gibbs et al., 1999). L- amino acid transporter activity which present in intestinal membrane is immature in young children (>5yrs) in comparison to older children and adult, This transporter responsible for absorption of some drugs for example gabapentin (Haig et al., 2001). P-glycoprotein (P-gp) is an efflux transporter that also plays a part in intestinal absorption. An analysis of P-gp expression in human intestinal tissue found relatively low levels in the neonatal group. The expression increased with age to reach maximum levels in young adults (15-38 years of age). The study also found decreased levels (half the maximal adult levels) in older individuals (67-85 years) (Miki et al., 2005).

Table (1): Factors affecting absorption in neonates and infants

Difference Physiologic factor compared to Consequences Examples of drugs adults

Weak acids–decreased Phenytoin, phenobarbital, bioavailability Gastric pH Higher ganciclovir, penicillin G, Weak bases–increased ampicillin bioavailability

Phenobarbital, digoxin, Gastric emptying time Prolonged Delayed absorption sulfonamide

Percutaneous absorption & Increased Higher Steroids hydration of epidermis bioavailability

Intramuscular absorption Variable Unknown ------& muscle blood flow

(Adapted from Lu et al., 2014)

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Developmental changes also can alter the absorption of drugs by other extravascular routes. Percutaneous absorption of drugs through skin may be high in newborns and infants owing to several factors including: better hydration of the epidermis, greater perfusion of the subcutaneous layer, and the larger ratio of total the body surface area (BSA) to body mass compared to adults. Thus, topically applied steroids in newborns and infants can result in unanticipated systemic absorption and has resulted in toxic effects in some instances (Furue et al., 2003). The absorption of intramuscularly administered drugs may be delayed in infant as a result of reduced blood flow to skeletal muscles (Tetelbaum et al., 2005), less muscular mass and a higher proportion of water (Strolin et al., 2005).

Rectal Administration is a useful route if the patient is unable to take drugs by mouth and the intravenous administration is difficult. The rectal area is small but well vascularized, and the absorption occurs through superior, media and inferior hemorrhoidal veins. The rectal route is not much modified by maturation. The local pH of the rectum is close to neutral in adults, but alkaline in most children (Bartelink et al., 2006).

II. Distribution: After absorption, a xenobiotic is distributed to various body compartments according to its physiochemical properties, such as molecular size, ionization constant, and relative aqueous and lipid solubility and factors related to our bodies such as; the presence and location of drug transporters, protein binding, systemic pH, and overall tissue perfusion. Age-dependent changes in drug volume of distribution which related to changes in body composition (water, fat) and nutritional status (Fernandez et al., 2011 & Sandritter et al., 2017). A drug’s volume of distribution is important because it controls the value of a loading dose, and along with a drug’s clearance, it determines a drug’s half-life which determined by tissue binding, plasma protein binding, and the physiochemical properties of the drug, such as lipid and water solubility, which impact the body compartments that a drug can access (Rosenbaum, 2011).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Fernandez et al., (2011), stated that several of the processes involved in the distribution of drugs are clearly different in neonates and infants when compared to adults:

1. Membrane permeability and Blood–Brain Barrier: Membrane permeability in the neonates is much higher than the older children and adults. The blood–brain barrier is immature in newborns and neonates and more permeable to drugs, which may lead to higher drug concentrations in the central nervous system of very young children For example, first-generation H-1 receptors are lipophilic and can rapidly cross the blood–brain barrier in newborns and neonates than older children and adults (Benedetti & Baltes, 2003).

At birth, the blood-brain barrier (BBB) is still not fully mature and medicinal products may gain access to the central nervous system with resultant toxicity. This neonatal greater permeability in turn allows some drugs with low penetration capacity to achieve higher concentrations in brain than those reached in children or adults, as it has been described with amphotericin B (Cohen et al., 2009). As the brain is disproportionately large in young children, this factor, combined with the immaturity of the BBB, leads to a significant additional volume for chemical partitioning. The volume of the central nervous system (CNS) is relatively large in younger children and does not correlate well with body surface area (BSA) in the pediatric population since CNS volume reaches 80-90% of adult values by age 4-6 years, yet BSA does not reach adult values until about age 16-18 years. This suggests that BSA dosing of intrathecal therapy would yield relatively lower cerebrospinal fluid concentrations (CFC) in younger children versus adolescents and adults. For example, CFC following the intrathecal injection of methotrexate (based on BSA and administered to patients ranging 3-39 years old) were found to vary 100-fold, with lower concentrations observed in young children in their sample (Seyberth et al., 2011).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

2. Plasma protein binding: Plasma protein binding of compounds is dependent on the amount of available binding proteins, the number of available binding sites, the affinity constant of the drug for the protein(s), and the presence of pathophysiological conditions or endogenous compounds that may alter the drug-protein binding interaction. In general, acidic drugs mainly bind to albumin, whereas basic drugs bind to globulins, α1-acid glycoprotein (AAG) and lipoproteins (Strolin et al., 2005).

Frequently, the unbound fraction is higher in neonates and infants for several reasons. First, the concentration of binding proteins may be reduced. Moreover, these proteins are qualitatively different and generally have lower binding capacities, especially in neonates (Kearns et al., 2003).

At birth, Human serum albumin (HSA) concentrations are closer to adults (75–80 %), but α1-acid glycoprotein concentration is half of the adult concentrations. The concentration of HSA in cord blood is 36 g/L as compared to 45 g/L in adult plasma, while α1-acid glycoprotein concentration in cord blood is 0.24 g/L as compared to 0.6 g/L in adult plasma (Alcorn et al., 2002).

3. Body water: In very young infants, the total body water is high (80-90% of the body weight (BW)) while fat content is low (10-15% BW). The amount of total body water decreases to 55-60% by adulthood (Table 2). The extracellular water content is about 45% in neonates, and especially large in neonates with low birth weights, compared with 20% in adulthood (Tetelbaum et al., 2005).

These changes will result in a relatively higher volume of distribution of water-soluble drugs in pediatric population than in adulthood, such as gentamicin (0.5-1.2 l/Kg in neonates and infants and 0.2-0.3 l/Kg in adults) (Strolin et al., 2005) and similar or lower for fat-soluble drugs such as diazepam (Bartelink et al., 2006).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Table (2): Age-related changes in body composition. Fat and water values are reported as a percentage of total body mass

Age Body mass (Kg) Fat Water Newborn 3.5 14 74 4 months 7 27 61.5 12 months 10.5 24.5 60.5 Adult 70 15 - 25 55 - 60

(Adapted from Alcorn et al., 2003)

III. Metabolism: Metabolism (biotransformation) is the sum of all biochemical reactions by which endogenous and exogenous compounds are converted to metabolites. The goal is to eliminate exogenous compounds and waste products of metabolism from the body. After birth, drug-metabolizing enzymes are immature. On the contrary, in children between 1 and 6 years of age, enzymatic activity is in some cases relatively higher than that in adults. Drug clearance in this age group is increased and half-life is shortened, so higher weight- corrected doses compared with adults are needed for drugs eliminated by some of the cytochromes P450 (CYPs) (Anderson, 2010). The liver is quantitatively by far the most important organ for drug metabolism. It constitutes 5% of the BW at birth but only 2% in adults (de Wildt et al., 2003). The hepatic clearance depends on several factors, including blood flow, hepatic enzyme activities (intrinsic metabolism), transport systems and plasma protein binding. Blood flow and drug-metabolizing enzymes are reduced in children; the former reaches adult rates by around one year of age (Anderson & Lynn, 2009).

The primary objective of drug metabolism is to transform drugs into more water soluble substances to facilitate their excretion. This process occurs primarily in liver hepatocytes to generate metabolites that are inactive and relatively non-toxic; however, metabolites may occasionally be the

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics source of toxic effects. Drug metabolism mechanisms can be classified into phase I, involving structural alteration of the drug molecule, and phase II reactions, consisting of conjugation with another often more water-soluble moiety (Hines, 2007). At birth, both phase I and II metabolic enzymes may be immature. In children, the different capacity to metabolize drugs may result in higher or lower drug plasma levels than those reached in adults (Blanco et al., 2000).

1. Phase I metabolism enzymes: Phase I reactions can be oxidation, reduction and hydrolysis. Oxidative reactions are the most important and frequently, though not necessarily, cytochrome P450 enzymes -dependent (Blanco et al., 2000)

Cytochrome P450 enzymes (CYPs): CYPs are undoubtedly the most important enzymes of phase I xenobiotic metabolism. Their primary goal is most frequently the hydroxylation of drug substrates, which results in an increase in their solubility (Anzenbacher & Zanger, 2012). These enzymes metabolize between 70% and 80% of the human drugs used, and the metabolism mediated by these enzymes can quite often be the basis of drug interactions (Zanger & Schwab, 2013). CYPs are characterized by an extremely broad substrate specificity and ubiquitous localization. In the prenatal development, hepatobiliary morphogenesis occurs during the first 10 weeks of gestation. Smooth endoplasmic reticulum where the majority of CYPs are found begins to be formed after the 10th week (Ring et al., 1999).

The most important forms of CYPs involved in the conversion of foreign compounds include CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and, in newborns and children, CYP3A7. The individual forms differ in their specificity to various substrates as well as in their ontogenetic development (Hines, 2008).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

i. The inter-individual variability of CYP1A1/2 enzymes activity determined by phenotyping with the use of a marker substrate (caffeine) is of major importance. Although great effort has been made in this field, this variability cannot be explained by a polymorphism in the CYP1A2 gene. Publications dealing with the presence and activity of these two CYPs in terms of ontogeny have shown that the CYP1A1 form is present in the fetus in the first trimester of development (Anderson, 2012). As regards caffeine and theophylline, the situation is different. Postnatally, the CYP1A2 activity against these substrates is also very low but rapidly reaches adult values, 4–5 months after birth. In older children, theophylline clearance is even higher than that in the adult (de Wildt, 2011).

ii. The whole CYP3A subfamily is represented the most in the human liver. The most important form is CYP3A4 that, along with CYP3A5, is expressed extrahepatically, namely in the small intestine. Their presence in this organ has clinical consequences since the inhibition of intestinal enzymes by medications or food can very significantly increase the levels of the medications administered e.g. calcium channel blockers (Gero´nimo-Pardo et al., 2005) or sildenafil (Jetter et al., 2002). The activity of CYP3A4 in the fetus and in the newborn is very low; however, between 6 and 12 months of age, the expression of CYP3A4 mRNA reaches 50% of adult values (de Wildt et al., 1999).

iii. The best-known substrates include ethanol and acetaminophen. (Coen, 2015). According to the study of Johnsrud et al. (2003), the amount of the enzyme increases very rapidly after birth and after three months, the relative content is comparable to that in the adult.

iv. The effect of genetic polymorphism is most evident on cytochrome P450 2D6. The abundance of alleles varies considerably across ethnic groups, (Ingelman-Sundberg, 2005). Genetic polymorphism in slow

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

metabolizers has very serious clinical consequences, e.g. low analgesic efficacy of tramadol or codeine (Armstrong et al., 2003) & (Stamer & Stu¨ber, 2007). An ultrafast metabolizer case was described wherein the administration of an increased dose of codeine in a breastfeeding woman resulted in the poisoning of her breastfed neonate with morphine, a codeine metabolite (Koren et al., 2006). The proportion of CYP2D6 in the adult human liver is around 5%, and it is involved in the metabolism of approximately 20% of drugs. Its catalytic activity in the fetal liver is about 1% in comparison with that in the adult (Jacqz- Aigrain et al., 2003).

v. The human CYP2C subfamily consists of three main enzymes: CYP2C8, CYP2C9 and CYP2C19 (Guengerich, 2003). CYP2C8, unlike the others, is of no crucial importance in pediatric pharmacology. Two years postnatal age had mature protein levels of CYP2C9 while, the values of CYP2C19 showed a linear increase till the age of 10 years when they were comparable to those in the adult (Koukouritaki et al., 2004). Typical CYP2C9 substrates include; ibuprofen, diclofenac and other non-steroidal anti-inflammatory drugs, sartans and S-warfarin. CYP2C19 substrates are, for example, proton pump inhibitors, citalopram, R-warfarin, phenytoin and propranolol (Flockhart, 2007).

Flavin-containing monooxygenases (FMOs) Similarly to CYPs, FMOs are microsomal enzymes. The human genome contains five genes encoding five enzymes (designated FMO1– FMO5). The most important form in the adult is FMO3 that occurs in the liver. FMOs metabolize drugs containing nucleophilic nitrogen, sulfur or phosphorus in their molecule, with their substrate specificity frequently overlapping with that of CYPs (Cashman & Zhang, 2006). The most important substrates are itopride, promethazine, chlorpromazine, clozapine, methamphetamine, olanzapine and imipramine (Krueger et al., 2005).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

In the prenatal development, FMO1, which is the main hepatic form in the fetus, plays a major role. In the adult, this form occurs in the kidneys. After birth, its activity and amount in the liver decrease rapidly, it was undetectable as early as 3 days postnatally. By contrast, FMO3, the main hepatic form in the adult, is detectable in the first trimester only. During childhood, its activity rises gradually until adulthood, reaching some 50% of the adult activity between the first and 10th years of life (Koukouritaki et al., 2002) & (Yeung et al., 2000).

2- Phase II metabolism enzymes: The role of phase II enzymes is to conjugate the metabolite produced in phase I with a product of endogenous metabolism. Research into conjugation reactions significantly lags behind that into phase I enzymes. However, the enzymes involved in these reactions are no less important, as evidenced by the number of drug interactions (McCarver et al., 2002).

Uridine 50-diphospho-glucuronosyltransferases (UGTs) The most important phase II enzymes are uridine 50-diphospho- glucuronosyltransferases (UGTs). Approximately 50% of medications are subject to this conjugation . There are 22 known types of UGT in humans (Sneitz et al., 2009). In the newborn, UGT1A1, inducible by, e.g. phenobarbital and responsible for bilirubin conjugation, is of particular importance. The absence of the enzyme results in Crigler–Najjar syndrome, with a milder form being congenital hyperbilirubinemia or Gilberts disease (Clarke et al., 1997). Also, of major clinical significance is the UGT2B7 form, involved in the conjugation of morphine and chloramphenicol. Mainly postnatally, some activity can be detected, with full activity being achieved by 2 years of age (Kiang et al., 2005).

Sulphotransferases (STs) The data on their development and maturation are limited and not completely clear. STs' activity in the fetus, newborn and infant is substantial and conjugation with sulfates is thus relatively effective after birth and is developed faster than UGTs' activity (Yokoi, 2009).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Glutathione S-transferases (GST) Also represent a major group of enzymes responsible for detoxification of a number of potentially toxic drugs and their metabolites. N- acetyltransferases (NATs) include two types of enzymes (NAT1 and NAT2).Unfortunately, the data on the development of these enzymes are very limited (McCarver et al., 2002). According to Vranković (2016) study, there is impairment in GST activity with aging in his experimental sample.

According to the aforementioned developmental changes in the metabolism of xenobiotics, it can be detected that indomethacin and phenobarbital are substrates of CYP2C9, caffeine is metabolized by CYP1A2 and NAT2, and morphine is a specific substrate for UGT2B7. The capability to metabolize these compounds is reduced, particularly in the newborn, and may result in an increase in their toxicity (Johnson, 2003 & Seyberth et al., 2011).

IV. Excretion: Excretion of a xenobiotics involves the processes by which the parent xenobiotics and its metabolites are eliminated from the body. It is mainly accomplished by the kidneys, as well as the bile, feces, lungs and the like. The excretion rate is highly variable and can be influenced by numerous factors both on the part of the drug and the patient. A number of xenobiotics, including penicillins, cephalosporins, digoxin and aminoglycosides, are excreted by the kidneys in an unaltered form. All of them are filtered by the glomeruli, with some of them also being reabsorbed and excreted by the tubular cells (e.g. penicillin, cephalosporin and phenobarbital) (Koren, 1997).

Renal function maturation is a dynamic process that starts at 9 weeks of gestation and is completed at the age of 2 years. Such a development is of course determined by proper nephrogenesis that is completed at 36 weeks of gestation (van den Anker et al., 1995). Renal excretion is accomplished by glomerular filtration (GF) and active tubular secretion. Passive and active

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics tubular reabsorption also contribute to the outcome. At birth, both the GF and tubular secretion processes are reduced; however, filtration is relatively more developed. In preterm infants, the number of glomeruli is lower than in full- term ones, whose number of glomeruli is equal to that in adults. The maturation process of renal structure and function is associated with tubular elongation and maturation, increased renal blood flow and improved filtration efficiency. Moreover, blood flow is shifted from the deeper to the more superficial nephrons. Improvement in the GF rate (GFR), depends on both the gestational and postnatal age (Koren, 1997).

At birth, GFR normalized to body surface area, is 10–15 ml/min/m2 in the full-term infant, but increases to 20–30 ml/min/m2 within the first 2 weeks of life. By 6 months of age, infant GFR, normalized to body surface area has approached adult levels (73 ml/min/m2) (Alcorn, 2003).

Tubular secretion is also insufficient after birth, particularly due to poor perfusion and undeveloped energy supply. Values comparable to those in the adult are achieved as late as 24 months of age. It is generally assumed that drugs that are metabolically inactivated in the liver are not influenced by reduced renal function. In most cases, however, the metabolite (whether active or inactive) is eliminated by GF or tubular secretion in the kidney. For instance, the metabolite of chloramphenicol is mainly eliminated by the renal tubules. Reduced tubular secretion in preterm infants can result in increased plasma concentrations of the inactive metabolite, but owing to the enterohepatic circulation there can be an increase in the concentration of the initial drug (Koren, 1997).

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

TOXICODYNAMICS

Two Types of Factors Affecting Toxicodynamics: 1. Intrinsic factors: Include; The density of receptors on the cell surface, the process of signal transmission by second messengers, and factors that control gene translation and protein production. Xenobiotic response is also affected by the duration of effect, which is determined by the time that a xenobioticis engaged not only on the receptor but also on intracellular signaling and gene regulation. For some xenobiotics, such as opiates, tolerance can develop, leading to decreased effectiveness with continued use unless the dosage is increased (Anderson & Lynn, 2009).

Tolerance is also commonly seen in patients taking stimulant medications (e.g., amphetamines, methylphenidates) for attention- deficit/ hyperactivity disorder (ADHD). Both toxicokinetics (TK) and toxicodynamics (TD) are important in determining the effect of xenobiotics (Ashok et al., 2017).

2. Extrinsic factors such as environmental exposures or concomitant medications can affect the efficacy of a medication. Exposure to tobacco smoking can induce CYP1A2, resulting in increased enzymatic activity, higher clearance, lower plasma levels, and efficacy for some drugs (e.g., clozapine, imipramine, amitriptyline, clomipramine, duloxetine, fluvoxamine, and mirtazapine (Sandritter et al., 2017).

True Pharmacodynamic Differences in Children: Children’s responses to drugs have much in common with the responses in adults. The perception that drug effects differ in children arises because the drugs have not been adequately studied in paediatric populations who have size and maturation related effects as well as different diseases.

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

Neonates and infant, however, often have altered PD (Stephenson, 2005). The minimal alveolar concentration for almost all anaesthetic vapours is less in neonates than in infancy, which is in turn greater than that observed in children and adults (Lerman, 1992).

In some cases, stage of development can alter the action of, and response to a drug that is a truly age-dependent difference in pharmacodynamics. This may be true of both the desired action and adverse events. Furthermore, and exclusively to fetal life and childhood, a drug can also alter development, temporarily or permanently ‘programming’ (i.e. permanent effects result from a stimulus applied at a sensitive point in development, often in fetal or neonatal life). Corticosteroids are used to illustrate the concept of programming. Examples of age-dependent adverse drug events are Valproate hepatotoxicity increased in young children, Thalidomide only causes "phocomelia" whilst the limb is forming, and Grey baby syndrome – chloramphenicol in young children (Stephenson, 2005). Also, age-dependent difference in pharmacodynamics with warfarin. The augmented response to warfarin in children should be taken into account in estimating warfarin doses for children (Takahashi et al., 2000).

Measurement of PD End Points: Outcome measures are more difficult to assess in neonates and infants than in children or adults. Measurement techniques, disease and pathology differences, inhomogeneous groups, recruitment issues, ethical considerations and end-point definition for establishing efficacy and safety confuse data interpretation (Baber, 2005).

Stephenson, (2005) stated that if a gastro-protective drug has already shown efficacy in randomized controlled trials involving thousands of adults with duodenal ulcer disease (phase 3 studies), can we use measurement of gastric pH (phase 2 study) to suggest efficacy in children and not undertake equally large randomized controlled trials? This will only be possible for the

REVIEW OF LITERATURE

Chapter I: Pediatric Toxicokinetics & Toxicodynamics

‘same’ disease – i.e. duodenal ulcer disease – and not extrapolation to, for example, gastro-oesophageal reflux. Moreover, it will only be plausible for a disease in which we can show the same pathological process, ideally by tissue diagnosis from biopsy samples, not necessarily for a disease which has the same name in adult and paediatric patients.

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

COMMON POISONS IN PEDIATRIC TOXICITY

HOUSEHOLD PRODUCTS

It include all product present and used in house. Among the thousands of harmless products available for household, very few are hazardous. Even then, poisoning with these substances is one of the common modes of poisoning all around. Household agents can be also classified according to their chemical natures as in Table (3) (Chowdhury & Ruhan, 2016).

Table (3): Household agents classified according to their chemical natures

Acid Alkaline Volatile substancesOthers Toilet cleaner Sodium Perfume Nail polish Hair colour hypochlorite Kerosene Nail polish Phenol Hydrogen peroxide Petrol remover Antiseptic Shaving gel/foam Paint thinner Talcum powder solution After shave lotion Paintbrush cleaner Button battery Sterilizing tablet Hair remover Turpentine Glue Vinegar Shampoo substitute

(Chowdhury & Ruhan, 2016)

I. Corrosives: Corrosive agents are broadly divided into acids, alkalis, and other harmful chemicals (Ramasamy & Gumaste, 2003). Corrosives have the capacity to tissue injury on contact by a chemical reaction most commonly affecting gastrointestinal tract, respiratory system and eyes (Naik & Vadivelan, 2012). This injuries are depend upon the type, amount, and concentration of the material consumed, as well as the contact time and chemical reaction with the tissue site. Thus, the potential respiratory, gastrointestinal, and upper airway injuries result in varying degrees of physiologic impairment (Miller et al., 2016).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Ingestion of corrosive chemicals in children is one of the most common causes of poisoning (Mowry et al., 2014). Most ingestions are due to parent’s lack of knowledge of the hazards of corrosive substances kept in the house, and the availability of chemicals in and around houses, combined with the natural curiosity of children (Contini et al., 2009).

Mechanism of action: Acids cause coagulation necrosis with eschar formation that may limit substance penetration and injury depth. Conversely alkalis combine with tissue proteins and cause liquefactive necrosis, saponification of fats, dehydration of tissues and thrombosis of blood vessels resulting in deeper tissue injury. All of them produce their effect through extraction of water then liberation of heat which cause varies injuries as in Figure (1) (Contini & Scarpignato, 2013).

Fig. (1): Mechanism of action of corrosive and how causing tissue destruction (Poinern et al., 2012)

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Clinical picture: The most common symptoms are related to the local irritative/ corrosive effects on the aerodigestive tract (Chibishev et al., 2014).

Children and teenagers who have ingested a caustic material are usually brought to the hospital very quickly. The patient can have respiratory distress and stridor due to laryngeal involvement, vomiting, dysphagia, drooling, pain abdomen, and refusal to drink. Local skin burn can be seen because of spillage of the corrosive agent. The lips, mouth and oropharynx may be damaged by caustic liquids, but lack of visible damage in the mouth does not preclude injury to esophagus and stomach. In cases of severe insult patient can present in shock (Elshabrawi & A-kader, 2011).

Investigations: a) Upper gastrointestinal endoscopy should be performed early (within 24 hours) to define the extent of injury, i.e. perforation or stricture, and guide appropriate therapy (Contini & Scarpignato, 2013). The extent of injury can be graded according to endoscopy findings. Grading system for corrosive burns of the alimentary tract with endoscopy as in Table (4).

Table (4): Shows Grading system for corrosive burns of the alimentary tract with endoscopy

Grade Features 0 Normal mucosa I Erythema and edema only IIa Localized superficial ulcers, bleeding and exudates IIb indicates local or encircling deep ulceration IIIa focal necrosis IIIb extensive, circumferential necrosis

(Shub, 2015)

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric b) Radiology helps in detection of perforation and other corrosive injuries to the stomach. Perforation in the stomach can be noted by plain X-ray of abdomen taken in erect posture showing crescentic gas shadows under both domes of the diaphragm (Park, 2014). c) Biochemical examination of the blood like CBC, serum electrolyte, arterial blood gas (ABG) analysis. It may reveal features of infection, acidosis, respiratory failure, septicaemia. If damage to any specific organ occurs, e.g. the kidney and liver, the respective biochemical markers are significantly changed (Park, 2014).

Treatment: Patients with vague history and without symptoms or oral lesions should be observed only for a few hours, offered clear liquids and discharged home after instructing the family to seek medical advice if the child experiences any symptoms (Elshabrawi & A-kader, 2011).

In symptomatic patients supportive TTT should done first. Gastric lavage and induced emesis are contraindication. Neutralizing agents have not been proved safe in humans and are best avoided for fear of inducing a compounding injury secondary to exothermic reaction. .Nasogastric or nasojejunostomy tube should be placed under direct endoscopic vision for feeding purpose (Shub, 2015). Other supportive measures include broad spectrum IV antibiotics, proton pump inhibitors (PPI), antacid. Although the use of systemic steroid in treatment of corrosive esophagitis remains controversial, some reports have documented the advantage of high dose systemic steroid administration for prevention of stricture formation (Morikawa et al., 2008).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Emergent surgery is recommended if there is evidence of perforation. Patients with grade 0 injuries can be discharged immediately. Those with grade I or II require specific treatment. Patient with grade III must be carefully observed for perforation symptoms for at least 1 to 2 weeks in intensive care unit and adequate nutritional support is required (Park, 2014). Gastrostomy may be required for Grade IIIb lesions for nutritional support (Naik & Vadivelan, 2012).

II. Kerosene: Kerosene is a hydrocarbon product of petroleum distillate, made up of paraffin and naphthenes. In developing countries kerosene is commonly kept in the home, being extensively used for cooking, heating and lighting (Alazab et al., 2012). Hydrocarbon ingestions account for about 5% of all accidental poisonings and 25% of all fatal ingestions in children of less than five years of age. It is a serious cause of poisoning in the lower socio-economic group (Shotar, 2005).

Mechanism: It has weak corrosive action so cause gastrointestinal and respiratory tract irritation. While in large dose, it causes central nervous system depression (Basu, 2016). Sufficient evidence has demonstrated the rapid onset of symptoms after hydrocarbon vapor inhalation or liquid aspiration. Because of their high volatility, low viscosity, and low surface tension, hydrocarbons penetrate into distal airways and spread over a large area of lung tissue (Shotar, 2005).

Clinical picture: o Signs and symptoms of respiratory involvement usually begin within 30 minutes after aspiration and may progress during the first 24-48 hr and then subside in the following 1to 2 weeks (Al- Naddawi et al., 2009). Pulmonary lesions produced by these

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

substances present a combination of lung irritation with loss of surfactant and features of lipoid pneumonia. The etiology of CNS symptoms (headache, dizziness, drowsiness, restlessness, seizures, and coma) is not clear, but hypoxia has been suggested as the main cause (Lifshitz et al., 2003). Fever (38-40°c) due to body reaction to foreign substance which occur within hours after ingestion for as long as 10 days (George et al., 2004).

o Gastrointestinal involvement (nausea, vomiting, abdominal pain, and diarrhea) has been attributed to mucosal irritation (Chowdhury & Ruhan, 2016).

o Renal tubular acidosis, renal failure and toxic nephropathy can occur (Linden & Lovejoy, 1998).

Investigation: a) Chest X-ray should be done to every patient after 6-8 hours from the time of ingestion. It may show fine perihilar opacities, bi-basilar infiltrates and atelactasis which may coalesce to produce a picture of consolidation (Thalhammer et al., 2005). b) CBC especially the leucocytric count that will show leucocytosis within 1st 24 hour of admission (George et al., 2004). c) Renal function test in case of renal affection (Linden & Lovejoy, 1998).

Treatment: Supportive TTT, Clinical history and assessment are life saving. Medical care was mainly supportive. Asymptomatic cases: should be under observation for at least 6 hrs the discharge if no symptoms (Shotar, 2005). Fluid administration should be aimed at replacement of losses while taking are to avoid precipitating pulmonary edema caused by over hydration (Seymour & Henry, 2001).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Gastric lavage or emitting agents must be avoided because the procedures are dangerous with a high risk of aspiration (Bamouni et al., 1999). In symptomatic cases: Patients received antipyretics, intravenous fluids and electrolytes, and humidified oxygen when necessary and nebulized bronchodilators may be used with caution if bronchospasm is severe. Antibiotics were prescribed when supportive treatment proved insufficient or secondary bacterial infection was suspected (Lifshitz et al., 2003). Corticosteroid, activated charcoal, cathartics, mineral oil and olive oil have no beneficial effect (Benois et al., 2009).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

PESTICIDE

The universe of pesticide types and products is broad (Table 5). This review tries to focus on groups that have the greatest acute toxicity for children on the basis of historical experience and/or emerging evidence (Hore et al., 2005). There is an increase of pesticide exposure and poisoning in children around the world with consequent morbidity and mortality (Jayashree & Singhi, 2011).

Table (5): Major pesticide classes and selected examples

Pesticide Class Examples Organophosphate Parathion, Chlorpyrifos, Dichlorvos, Acephate, methyl- Parathion, malthion, phorate N-Methyl Carbamates Aldicarb, carbaryl, Carbofuran, Pirimicarb, propoxu Pyrethrins and Pyrethroids Permethrin, cyano- pyrethroids: deltamethrin, cypermethrin, fenvalerate Neonicotinoids Imidacloprid N-Phenylpyrazole Fipronil insecticide Phosphonate herbicides Glyphosate

(James, et al., 2012)

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

I. Organophosphorus: A common Pesticide Poisoning Organophosphates are the most commonly used pesticides and one of the available lethal toxicants. They have replaced organochlorines like DDT because of their effectiveness and non-persistence in the environment. As a result of their wide use and easy availability, they are involved in a greater number of intentional acute poisoning cases especially in the developing countries (Eddleston et al., 2002).

Toxicokinetics: Absorption varies by route of exposure. Organophosphorus (OP) compounds are absorbed by the skin as well as by the respiratory and gastrointestinal tracts (Mahdi & Kia, 2008).

The intrinsically reactive chemical nature of OP pesticides means that any dose entering the body is immediately liable to a number of biotransformations and reactions with tissue constituents. In view of the inherent instability of the OP pesticides, storage in human tissue is not expected to be prolonged (van der Schans et al., 2003). However, some OP pesticides are very lipophilic and may be taken into, and then released from fat depots over a period of many days (Balali & Balali, 2005).

Metabolism occurs principally by oxidation and hydrolysis by esterases, and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of OP pesticides may result in more or less toxic products. In general, phosphorothioates are not directly toxic, but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity (Balali & Balali, 2005).

The elimination of the products, mostly in the urine and in lesser amounts in the feces and expired air, is not delayed, so that rates of excretion usually reach a peak within two days and decline quite rapidly (Balali & Balali, 2005).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Mechanism of action: Organophosphates manifest their acute toxicity through the inhibition of cholinesterases, which includes acetylcholinesterase and butyryl- cholinesterase (pseudocholinesterase) (Kwong, 2002). Inhibition of acetylcholinesterase is the primary mechanism of toxicity. The central role of acetylcholinesterase is to terminate the signaling at cholinergic synapses by the breakdown of the neuro-transmitter acetylcholine into choline and acetic acid (Dvir et al., 2010).

Acetylcholinesterase is present in central nervous system, peripheral nervous system, neuromuscular junction and erythrocytes. If inhibitors like organophosphates inhibit the enzyme, it results in accumulation of acetylcholine at the synapses, thereby, causing overstimulation of acetylcholine receptors as in Figure (2) (Kwong, 2002).

Organophosphates inactivate the acetylcholinesterase by phosphorylation of the hydroxyl group of serine present at the active site (Selcen et al., 2004).

Fig. (2): Pesticide accumulation in synaptic cleft (1), AChE inhibition by pesticide (2), and constant activation of AChR (3) (Vargas-Bernal et al., 2012).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Clinical picture: Clinical manifestations of acute toxicity are the result of dysfunction at the cholinergic synapses and are divided into three phases namely initial cholinergic crisis, intermediate syndrome and delayed polyneuropathy (Fig. 3) (Sheemona et al., 2014).

The onset of toxicity varies from few minutes to several hours after exposure. including central nervous, cardiovascular, respiratory, gastrointestinal and musculoskeletal (Singh & Sharma, 2000).

1. Initial cholinergic crisis Symptoms produced by parasympathetic over stimulation, include increased secretions from salivary, lacrimal, bronchial, and gastrointestinal glands, increased peristaltic activity, bronchoconstriction, bradycardia and hypotension, miosis, and loss of visual acuity. Urinary and faecal incontinence occur secondary to loss of sphincter control. In severe cases, overwhelming tracheobronchial secretions can lead to respiratory compromise. In large doses, organophosphates produce muscle stimulation followed by paralysis because of a depolarizing block. Hyperglycaemia and glycosuria without ketonuria may also occur (Riordan et al., 2002).

2. Intermediate syndrome Yang & Deng, (2007), stated that it was first described by Senanayake and Karralliede. Manifestations are seen after 24–96 hrs of exposure when symptoms of acute cholinergic syndrome are not obvious, as follows: Respiratory muscle weakness including intercostal muscles, diaphragm and neck flexors. Weakness of proximal limb muscles and muscles innervated by motor cranial nerves. The degree and extent of muscle weakness vary with the patients. The incidence of this phenomenon is as high as 80%. It is the major cause of mortality, but its pathophysiology is unclear.

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Fig. (3): Algorithm of OP poisoning effects (Sheemona et al., 2014)

3. Organophosphate-induced delayed polyneuropathy It generally develops when high doses of the pesticide are ingested, and resulted in the inhibition of neuropathy target esterase (NTE), which is a serine ``esterase present in the nervous system (Dvir et al., 2010).

Characteristic features involve the degeneration of long axons in the peripheral and central nervous system. It usually develops 2–5 weeks after acute exposure of organophosphates (Jokanovic et al., 2002).

Investigations: According to El-Naggar et al., (2009), a) Plasma cholinesterase level ChE become the lower limit of normal level. After exposure to a toxic dose of anticholinesterase pesticide.

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric b) ABG is needed to assess cases of organophosphate toxicity. c) Routine labs to assess the general condition of patient.

Treatment: General measures Standard treatment, involves removal of unabsorbed poison by decontamination of the skin. Gastric lavage is performed in the case of ingestion and also activated charcoal is administered. In patients, gastric lavage should be performed within 2 hrs of ingestion of organophosphate poison (Eddleston et al., 2008b). Supportive measures involve maintaining the ventilation, cardiac rhythms and blood pressure (Jokanović, 2009)

Decontamination: Gastric lavage is done to remove gastric content. By contrast, gastric lavage have potential serious complications if performed in non-consenting patients or unconscious patients without airway protection (Eddleston et al., 2007). Activated charcoal studies indicate that single or multiple doses of activated charcoal are safe in pesticide poisoned patients, including patients receiving appropriate amounts of atropine (Eddleston et al., 2008b).

Specific antidote a. Atropine: Reverse the hyperstimulation caused by accumulation of excessive acetylcholine at the muscarinic receptors thereby reducing the symptoms. However, it is ineffective in managing nicotinic receptor mediated manifestations (Eddleston et al., 2008a). Injection of 1.8-3 mg (3-5 ml) of atropine, bolus. Then checking three things after five minutes: pulse, blood pressure and chest crackles. Doubling of atropine dose every five minutes if these objectives has not achieved . Reviewing the patient every 5 min. Once these parameters start improving, last same or smaller dose of atropine should be repeated (Buckley et al., 2005).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric b. Oximes: Oximes known as cholinesterase reactivators are used for reactivation of organophosphate-inhibited acetylcholinesterase. They being highly nucleophilic, displace the phosphoryl moiety from the phosphorylated enzyme and reactivate the enzyme. The normal activity of the nicotinic neuromuscular junction is thus restored (Jokanović & Prostran, 2009). The recommended dose of pralidoxime according to WHO guidelines is initially given as a bolus of 30 mg/Kg followed by infusion of 8 mg/Kg/h until clinical improvement (Eddleston et al., 2004b).

c. Role of magnesium sulfate (MgSO4): It is concluded that administration

of MgSO4, in a dose of 4 g/day concurrent to conventional therapy, in OP acute human poisoning is beneficial, by reducing the hospitalization days and rate of mortality (Abdolkarim et al., 2004).

II. Carbamates: Mechanism of action: The mechanism of carbamate poisoning involves carbamylating of the active site of acetylcholinesterase leading to the inactivation of this essential enzyme which has an important role in nervous system of humans, and other animal species (Ecobichon, 2001). Acetylcholinesterase becomes progressively inhibited and is not further capable of hydrolyzing acetylcholine to choline and acetic acid (Jokanovic, 2009).

Clinical picture: o Ingestion or inhalation of carbamates results in a more rapid onset of clinical effects as compared with dermal exposure. Acute carbamate poisoning episodes were described among pesticide sprayers due to inadequate personal protection (Jensen et al., 2010). o The main clinical manifestations of carbamate intoxication are muscarinic signs (miosis, salivation, sweating, lacrimation, rhinorrhea, abdominal cramping, vomiting, diarrhea, urinary incontinence, bronchospasm, dyspnea, hypoxemia, bradycardia,

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

bronchial secretions, pulmonary edema and respiratory failure), nicotinic signs (less frequent; muscular twitching, fasciculations, muscle weakness including the respiratory muscles’ paralysis, tachycardia and hypertension) and central nervous system signs "rare" (Rosman et al., 2009).

Investigations: According to El-Naggar et al. (2009) a) Plasma cholinesterase level ChE become the lower limit of normal level. b) After exposure to a toxic dose of anticholinesterase pesticide c) ABG is needed to asses cases of organophosphate. d) Routine labs to asses the general condition of patient.

Treatment: o The medical management of carbamate poisoning consists of supportive measures and specific antidotal treatment, that is, the anticholinergic compound atropine. Treatment likes organophosphate treatment but with a very rapid recovery (Jokanovic, 2009). o Recovery without medical treatment of cases of accidental over- exposure with various carbamate pesticides spontaneously occurred, generally, within 4 h of exposure. o For accidental or intentional poisoning that produced symptoms such as visual disturbances, profuse sweating, abdominal pain, incoordination, fasciculations, breathing difficulties, or changes in pulse rate, treatment with atropine combined with general supportive treatment, such as artificial respiration and administration of fluids, has resulted in recovery of individuals within 1 day (Rosman et al., 2009). o Oximes have been tested in experimental studies and have been shown to be beneficial, alone and/or with atropine (Jokanovic, 2009).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

DRUG OF ABUSE

Drug abuse and its consequences remain a significant public health issue. An increasing number of individuals are present in the emergency room with life-threatening drug intoxication. It include a lot of drugs such as tramadol, cannabinoids, alcohol, benodiazepine and so on (Akerele & Olupona, 2017).

I. Cannabis Cannabis, in its various forms (Marijuana, hashish, and hash oil) is derived from the plant Cannabis, and may be absorbed into the body by inhalation of smoke or by ingestion (Bates & Blakely, 1999). Cannabis as the most prevalent drug of abuse in Egypt (Hamdi et al., 2013).

Mechanism of action: The psychotropic effects of its main active component ∆9-tetrahydrocannabinol (∆9-THC) are mediated primarily by the G protein-coupled CB1 cannabinoid receptors. CB1 receptors are localized mainly in neurons of the CNS and in the periphery. The primary effect of cannabinoids on neurons is a CB1 receptor-mediated inhibition of synaptic transmission. Cannabinoids also target CB2 receptors, which are located typically in tissues of the immune system. CB1 and CB2 receptors can also be activated by the endogenous cannabinoids (endocannabinoid) anandamide and 2- arachidonoylglycerol as shown in Fig. (4) (Hermanns-Clausen et al., 2013).

Fig. (4): Mechanism of action of cannabis (Ron Marczyk, 2013)

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Clinical picture: o Cannabis and THC acute toxicity can cause dizziness, sedation, intoxication, transient impairment of sensory and perceptual functions, clumsiness, dry mouth, lowered blood pressure, or increased heart rate (Robson, 2001). o Cannabis produces euphoria and relaxation, perceptual alterations, time distortion, and the intensification of ordinary sensory experiences. Cannabis smoking or ingestion of THC increases heart rate by 20–50% within a few minutes ; this effect lasts for up to 3 h. Blood pressure is increased while the person is sitting, and decreased while standing (Hall & Solowij, 1998)

Investigations: a) Cannabinoids can be detected in plasma or urine. Enzyme-multiplied immunoassay technique (EMIT) and radioimmunoassay (RIA) are routinely available; gas chromatography–mass spectrometry (GC-MS) is the most specific assay and is used as the reference method (Hoffman, 2006). b) Some patients, particularly children, may require further testing if exposure is unknown, including rapid blood glucose, electrolytes, blood gas analysis, and neuroimaging (e.g., computed tomography of the head). Neuroimaging should be avoided in known cannabis exposures unless focal neurologic findings are also present or concerns for other etiologies such as head trauma exist (Turner & Agrawal, 2017).

Treatment: The treatment for cannabis intoxication is symptomatic management. The extent of management has numerous factors, including an age of individual and amount of cannabis ingested. In cannabis-induced psychotic disorders, it requires typically 24 hours for safe detoxification, but sometimes longer if persistent psychosis or unstable vital signs occur (Turner & Agrawal, 2017).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

II. Tramadol: Tramadol seems a very promising drug in pediatric pain treatment, having an analgesic potency intermediate between that of non-steroidal anti- inflammatory drugs NSAIDs and opioids. Several forms of systemic preparations such as I.V, tablet, and drop make its use easier in children. Tramadol should be one of the options in the multimodal pain treatment approach in postoperative and chronic pain in children (Bozkurt, 2005).

Accidental ingestion of tramadol is well tolerated by children (Marquardt et al., 2005). Children 2 to 3 months of age or younger lack the motor and cognitive ability to ingest toxins on their own. Parents have intentionally administered other sedatives or narcotics to infants to calm or quiet them. This may have been the motivation for the intentional tramadol administration in certain cases, while older infants with a developed ability to grasp and transfer objects to their mouth can accidentally ingest toxins left within their reach. Subsequently, as infants gain mobility, they can get to the objects they ingest. Negligent supervision and medicine storage may play a role in these ingestions (Mazor et al., 2008).

Toxicokinetics: After oral administration, tramadol is rapidly and almost completely absorbed (Gong et al., 2014). The mean oral bioavailability of tramadol is only 65-70% due to the first-pass hepatic metabolism (Ardakani & Rouini, 2007). While it’s mean total bioavailability after rectal administration is (78%) (Leppert & Luczak, 2005).

Tramadol is rapidly distributed in the body, with a distribution half-life in the initial phase of 6 minutes, followed by a slower distribution phase with a half-life of 1.7 hour. The high total distribution volume of 306 liters after oral administration indicates high tissue affinity and the plasma protein binding is about 20% (Ardakani & Rouini, 2007). Tramadol passes the placental barrier, with umbilical venous plasma concentrations being 80% of

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric maternal concentration. Very small amounts (0.1%) of tramadol and O- demethylated metabolite (M1) are excreted in breast milk (Grond & Sablotzki, 2004).

Tramadol is extensively metabolized in the liver by demethylation, oxidation and conjugation (sulphation and glucuronidation) (Wu et al., 2002).

About 30% of an oral dose is excreted unchanged in the urine, and about 60% in the form of free and conjugated metabolites. The elimination half-life of racemic tramadol is approximately 6 hours, irrespective of the mode of administration, and about 8 hours for O-desmethyltramadol (M1) the main active metabolite (Baselt & Cravey, 2011).

Mechanism of action: The analgesic mechanism of action of tramadol includes both non- opioid components, i.e., noradrenergic and serotonergic components, and opioid components (Raffaet al., 2000) resulting in the activation of the descending inhibitory system (Rehni et al., 2008). Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of M1 to µ-opioid receptors. In several animal tests tramadol induced analgesia is only partially antagonized by the opiate antagonist naloxone (Pawar et al., 2015).

Tramadol has agonist effects at the GABA aminobutyric acid receptor

(GABAA) receptor (Shadnia et al., 2012). At higher doses it causes inhibition of GABAA receptors (Hara et al., 2005).

Tramadolhas also inhibitory effects on muscarinic M1 receptor function as well as inhibiting nicotinic acetyl choline receptors (AChR) functions (Shiraishi et al., 2002).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Clinical picture: The CNS manifestations are of the most common presentation of tramadol overdose ranging from CNS depression to lethargy and deep coma (Afshari et al., 2011). Seizure is the most clinical manifestation in tramadol poisoning (Rahimi et al., 2014).

Anxiety, agitation, confusion, ataxia, euphoria and hallucinations had also been reported as signs for tramadol toxicity (Gair & Kent, 2010) while respiratory depression is less pronounced (Marquardt et al., 2005).

Although a number of authors had reported that tramadol overdose elicits miosis (knaggs et al., 2004), mydriasis is reported in some cases. It was found that subjects with mydriasis are more prone to seizure. Mydriasis, therefore, may be useful as a predictive factor for seizures in tramadol overdose (Tashakori & Afshari, 2010).

Cardiovascular toxicity of tramadol seems to be limited to sinus tachycardia and hypertension. Hypotension has been reported following massive ingestions. Serious dysrhythmias are uncommon with tramadol alone (Gair & Kent, 2010). Acute pulmonary hypertension and right heart failure are the uncommon presentations reported in a young tramadol-overdosed patient (Garrett, 2004).

Serotonin syndrome (SS) is a potentially fatal syndrome due to increased synthesis, decreased metabolism, increased release, and reuptake inhibition of serotonin or direct agonism at the serotonin receptors (Kitson & Carr, 2005). Three key clinical features of this syndrome include: Neuromuscular hyperactivity, Autonomic hyperactivity and mental status changes (El-Okdi et al., 2014).

Severe cases may develop marked rigidity, trismus, rhabdomyolysis, coma, Disseminated Intravascular Coagulopathy (DIC), right heart failure and disturbances of electrolytes, transaminases and creatinine kinase (CK) (Garrett, 2004).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Investigation: (a) Detection of Tramadol Level in Samples: Tramadol and O-desmethyltramadol may be quantitated in blood, plasma or serum to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of traffic or other criminal violation or a sudden death (Karhu et al., 2007).

(b) Electrocardiographic changes in tramadol overdose: After tramadol overdose QRS prolongation, non-specific ST-segment and T-wave changes, first-degree atrioventricular block, atrial fibrillation, prolonged corrected QT intervals, and ventricular dysrhythmias may occur (Daubin et al., 2007).

(c) Blood glucose level: Tramadol can be associated with hypoglycemia, particularly in elderly or diabetic patients, or in those with renal insufficiency (Bourneet al., 2013).

Treatment: The treatment of tramadol overdose is mainly supportive (Afshari et al., 2011). Asymptomatic patients should be monitored for 6 hours after ingestion of regular release formulation and 12 hours after exposure to extended release products. Symptomatic patients should be monitored until symptoms resolve (Gair & Kent, 2010).

Supportive Treatment: Treatment should focus on conservative approaches including maintenance of airway, breathing, and circulation, oxygen therapy, fluid resuscitation, diazepam administration to control agitation and seizure (Afshari et al., 2011). Coma cocktail (Glucose, Thiamine 100 mg IV to patients with altered mental status, Naloxone should be given as an antidote) (Kleinschmidt et al., 2001).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

GIT Decontamination: Gastrointestinal decontamination should be performed in the patients who come within the first two hours post-ingestion and have no contra- indications (Shadnia et al., 2012).

In severe toxicities due to ingestion of large amounts of sustained- release drug, multiple dose activated charcoal should be considered if no contraindication exists (Raffa et al., 2000).

Opioid Antagonist (Naloxone): Naloxone is a pure opioid antagonist. It was the first opiate receptor antagonist introduced in clinical practice and has been widely used to antagonize the effects of opiate drugs. Most guidelines for treatment of opioid overdose recommend Naloxone as the first step of treatment after supportive care (Farzaneh et al., 2012a). Naloxone prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. The duration of action for Naloxone is shorter than that of most opioids, so patients must be closely monitored for recurrence of opioid toxicity when the antagonist effects of Naloxone wane and repeated doses may be required (Buck, 2002). a 2-mg bolus repeated every 5 min, followed by 0.4 mg every 2 to 3 min as needed (up to 24 mg total) dramatically reverses the CNS and respiratory depression (Barile, 2004).

Symptomatic Treatment: Symptomatic patients should be monitored until symptoms resolve. Monitor vital signs, monitor electrocardiogram in symptomatic patients, maintain fluid and electrolyte balance.

Seizures should be treated with benzodiazepines. Tachycardia and hypertension usually do not require treatment (Gair & Kent, 2010).

Intubation/ventilation and administration of naloxone are the treatments for tramadol-induced apnea (Hassanian-Moghaddam et al., 2013).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

MEDICATION

Unintentional childhood ingestion of medication is a well-recognized and potentially preventable problem that affects large numbers of children annually (Chien et al., 2003). At 3-5 years of age, the medications kept in cupboard or left open are the main causes of poisoning. Whereas, at school age and during adolescence, medication used for committing suicide are the main cause of poisoning (Mutlu, 2010).

Medications include many categories (Fig. 5) as analgesics (paracetamol and asprin) (Jepsen & Ryan, 2005), bronchodilators (theophylline), antiepleptics (tegretol and new generations) (Vajda, 2014), antihypertensive drugs (Hetterich et al., 2014) and so many drugs .

Medications

Bronchodilators Antihypertensive Analgesics (theophylline) and drugs (Hetterich et (paracetamol and antiepleptics (tegretol al., 2014) aspirin) (Fiona & and new generations) Mary, 2005) (Vajda, 2014)

Fig. (5): Show the common medications involved in child toxicity Here we will talk about the most common drugs involved in child toxicity.

I. Paracetamol Acetaminophen, or N-acetyl-para-aminophenol (APAP), remains one of the most commonly ingested xenobiotics, both intentionally and unintentionally. APAP is responsible for one-third of all pediatric emergency

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric department visits forum supervised over-the-counter liquid medication exposures in children younger than age 6 years. In addition, APAP is the cause of almost one-fifth of medication exposures involving oral over-the- counter solid medications, the common drug took alone (Michael & Michele, 2017). Children are more resistant to paracetamol-induced liver damage than adults (Riordan et al., 2002).

Toxicokinetics: Orally administered APAP is rapidly absorbed from the gastrointestinal tract, with complete absorption occurring within 4 hours, although coingestion with anticholinergic drugs such as diphenhydramine or opioids can delay absorption. Of greatest concern to the treating clinician is generation of the toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) (Péry et al., 2013).

In therapeutic dosing, the body has sufficient stores of glutathione (GSH) to reduce and detoxify NAPQI. In overdose, alternative metabolic pathways become saturated, and there is increased formation of NAPQI, leading to depletion of GSH and accumulation of NAPQI. As NAPQI accumulates, it binds to various cellular proteins, inducing hepatocellular death and liver inflammation (Larson et al., 2005).

Toxicity manifests as rising aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values. In addition, depletion of GSH leaves the body susceptible to endogenous reactive oxygen species, leading to further damage. Histologically, damage is most profound in the hepatic centri-lobular zone III due to the high concentration of the enzyme CYP2E1 (Péry et al., 2013).

Mechanism of action and toxicity: Paracetamol (acetaminophen) is generally considered to be a weak inhibitor of the synthesis of prostaglandins (PGs) (Graham et al., 2013). Acetaminophen metabolized to the toxic metabolite N-acetyl-p-benzo-

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric quinoneimine (NAPQI). This metabolite detoxified by glutathione (GSH). In overdose, alternative metabolic pathways become saturated, and there is increased formation of NAPQI, leading to depletion of GSH and accumulation of NAPQI as in Fig. (6) (Graham et al, .2013).

Fig. (6): Mechanism of paracetamol action and toxicity (Graham et al, .2013)

Clinical picture: The stages of paracetamol toxicity are listed in Table (6). Clinicians must have a high index of suspicion due to the absence of specific signs and symptoms early in intoxication. Often patients present without symptoms or with vague abdominal pain, nausea, and emesis. As the toxic metabolite (NAPQI) accumulates, evidence of liver injury, namely, elevation of AST and ALT serum concentrations and prolongation of prothrombin time/ International Normalized Ratio (Michael & Michele, 2017).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Table (6): Clinical Stages of Acetaminophen Toxicity

Time Stage Signs/Symptoms Labs Frame Nausea Normal 0-24 hours Vomiting AST/ALT, INR I Malaise Pallor Hepatotoxicity Rising AST/ALT 12-72 hours II Right upper quadrant INR normal/ elevated tenderness Fulminant hepatic failure AST/ALT >10,000 U/L (167 72-96 hours Encephalopathy mkat/L) Coma INR elevated III Elevated Cr Acidosis Lactemia Recovery Normalization of AST/ALT, > 96 hours IV INR As hepatic injury worsens and the synthetic capability of the liver is impaired, prothrombin time/INR increase. Eventually, multisystem organ failure develops, after which patients recover, receive liver transplant, or die

ALALT : Alanine aminotransferase AST : Aspartate aminotransferase, INR : International Normalized Ratio Cr : Creatinine (Michael & Michele, 2017)

Investigation: According to Algin & Erdogan, (2017) are; a) Urea, serum sodium, serum potassium, creatinine, glucose, liver function tests (bilirubin, alkaline phosphatase, ALT, AST, GGT, albumin, total protein), clotting screen, venous blood gas and lactate to check for acidosis. b) Serum AST or ALT, prothrombin time (or INR), electrolytes, urea, creatinine, venous pH, and lactate should be repeated at the end of intravenous therapy. This helps to determine if subsequent infusion of N- acetyl cysteine is necessary.

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric c) Higher levels of blood plasma acetaminophen levels at 4 hours after ingestion or later.

Treatment: Decontamination: Activated charcoal reduced the absorption of paracetamol when given within an hour of ingestion. In a study of patients with paracetamol overdose, those treated with charcoal were less likely to have serum concentrations predicting a high risk of hepatotoxicity. Other methods of gastric decontamination, including syrup of ipecac and gastric lavage, are less effective and are not usually recommended (Kozer and Koren, 2001).

Specific antidote: Cysteamine can prevent severe liver damage if given intravenously in adequate dosage within 10 h of ingestion, it causes unpleasant and occasionally alarming side-effects. Furthermore, it is not available commercially as a pharmaceutical product. Other available agents such as dimercaprol, penicillamine, and methionine are less effective and do not always prevent severe liver damage (Gupte, 2016).

Nacetyl cystein: Hepatic failure may be prevented by timely administration of N- acetylcysteine (NAC).Among 62 patients with paracetamol overdose treated with NAC intravenously within 10 hours of ingestion, only 1 had severe liver damage. In comparison, the rate of liver damage among historical controls treated only with supportive care was 58%. Oral treatment with NAC was also shown to be effective in preventing liver injury in cases of paracetamol overdose (Kozer & Koren, 2001).

NAC prevents paracetamol toxicity by serving as a glutathione precursor and by increasing sulphate conjugation. It also has an enhancing effect on intrahepatic microcirculation (Kigawa et al., 2000).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Protocol of administration according to Gupte, (2016) If the serum paracetamol level is less than 20 mg/ml and the ALT is less than 50 IU/L, then no treatment is necessary. However, if the ALT is more than 50IU/L and paracetamol level is more than 20 mg/ml, there is a risk that hepatotoxicity may progress and the child or young person should be commenced on N-acetyl cysteine immediately as per the oral paracetamol overdose protocol. Bloods should be repeated 12 hourly until the paracetamol level is less than 10 mg/ml and ALT has shown an improving trend.

NAC can also be started immediately or empirically on the discretion of the admitting clinician if: Patients present 8 hours or more after ingestion. Serum paracetamol level is not available within an 8-hour time window. There is uncertainty as to the timing of the overdose Patients are unconscious or have a suspected overdose.

The Rumack and Matthew nomogram of acetaminophen levels and time after dose was developed for prediction of risk in acute intoxications so that a low level does not eliminate the possibility of toxicity caused by chronic ingestion of acetaminophen. The health care provider should consider acetaminophen toxicity in any child who has received acetaminophen who has signs of acute hepatic dysfunction, even if acetaminophen levels are not in the toxic range. If the levels are in the toxic range after long-term treatment with acetaminophen, it is an ominous finding associated with a high risk of mortality (American Academy of Pediatrics, 2001).

II. Theophylline: Theophylline is a commonly used drug in the treatment of acute or chronic lung disease. Despite the considerable potential benefit of theophylline, its narrow therapeutic range and erratic absorption and elimination contribute to the potential for toxicity, which can have high morbidity and mortality (Charehsaz et al., 2011).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Toxicokinetics : The effects of oral theophylline are rapid and complete, with peak levels achieved at 2 h after administration (Moller et al., 2000). The level of binding to serum proteins is approximately 60%, and the volume of distribution is 0.5 l/Kg. In adults, 90% of theophylline is metabolized by liver cytochrome P450 (CYP450) 1A2, and in neonates, approximately 50% is excreted unchanged in the urine because of their immature hepatic function (Lowry et al., 2001).

Many factors are reported to affect CYP1A2 activity, such as single nucleotide polymorphisms of CYP1A2 and concurrent administration of drugs including phenytoin, phenobarbitone, erythromycin and quinolone antibiotics (Yim et al., 2013).

Therefore, variability in theophylline clearance may be explained in part by these factors. The elimination half-life of theophylline was 3.5 h in paediatric patients and 5–6 h in adults, and it was prolonged in the elderly (Yoon et al., 2006).

Mechanism of action: Theophylline is a methylxanthine similar to caffeine. The exact mechanism of action of theophylline is unknown. Most of its effects seem to involve its direct action as an adenosine antagonist. Clinically it causes stimulation of the central nervous system, vomiting center, myocardium, and renal blood flow as (Fig. 7) (Williams & Erickson, 2015).

Fig. (7): Action of theophylline (Peter, 2010)

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Clinical picture: o Toxic gastrointestinal effects of theophylline overdose include nausea, vomiting, Bleeding and metabolic disturbances (hypokalemia, hyperglycemia, and metabolic acidosis). o Cardiovascular effects include tachycardia and hypotension. o Central nervous system effects include seizures and coma (Williams & Erickson, 2015).

Investigations: a. Serum Na+ and K+ to detect electrolytes disturbance b. ABG as it cause metabolic acidosis. c. ECG it may show supraventricular arrhythmia. d. Theophylline level to support history of intake, the peak levels occurring within 2-3 h. But With extended-release theophylline, peak levels usually occur around 8-12 h. Cases of acute overdose have occurred, however, where peak levels are delayed for more than 24 hours (Fisher, 2015).

Treatment: Gastric decontamination with gastric lavage if the patient presents within 1-2 h of ingestion followed by administration of activated charcoal. Because theophylline undergoes enteroenteric recirculation (gut dialysis), multiple doses of charcoal can be beneficial. Because the patient often has intractable vomiting secondary to theophylline poisoning, powerful antiemetic agents may be required (Ellis, 2007). If the patient has severe toxicity, aggressive intervention with hemodialysis or charcoal hemoperfusion may be indicated. Indications for dialysis are summarized in Table (7) (Ghannoum et al., 2015).

REVIEW OF LITERATURE

Chapter II: Common Poisons in Pediatric

Table (7): Indications for hemodialysis/hemoperfusion with theophylline

Acute levels greater than100 u.g/mL Chronic levels greater than 60 u.g/mL Any level greater than 70 ug/mL, 4 hours post-ingestion with sustained-release formulation Any level greater than 40 u.g/mL when following conditions are present: Hypotension Inability to keep charcoal down/intractable vomiting Rising levels despite conventional therapy Seizures Ventricular dysrhythmias

(Williams & Erickson, 2015)

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

MANNER OF PEDIATRIC TOXICITY AND OTHER MEDICOLEGAL ASPECTS

Accidental and Intentional Toxicity

Acute poisoning in children is an important pediatric emergency and is a worldwide problem . The cause and poisoning type vary in different parts of the world and within the country also depending on factors such as education, demography, socioeconomic factors, customs, local belief as well as the ease of availability of pharmaceuticals and drugs (Narayan Reddy, 2008).

The majority of poisonings involving young children are classified as unintentional. In contrast, approximately one-half of poisoning exposures involving teenagers are intentional (Bronstein et al., 2010).

I- Unintentional (accidental) child toxicity: It is almost always in children under 5 year of age (Alazab, 2012). As children are curious about surrounding and explore their world with all their senses like taste and smell (Narayan Reddy, 2000). Poisoning may result from pica, thirst or hunger. Toxicity due to pharmaceutical agents may occur due to self-administration by parents for minor ailments, prescription of drugs by quack and due to the ignorance of doctor (Cheraghali & Taymori, 2006).

Toddlers are at increased risk of accidental poisoning because of their spontaneous activity, curiosity, innocence, mouthing of objects and imitation of adults. The incidence and to some extent causative agent vary from region to region and is largely influenced by the life style, socioeconomic status and culture habits of the people (Singh, 2007).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Most cases reported when parents or caregivers are not paying attention at home. The most common agents involved in poisoning are over- the-counter (OTC) medications, prescription medications, household products, pesticides, kerosene, poisonous plants and animal or insect bites (Lam, 2003). Most of accidental child toxicity occur at home (Juris, 2006), it involved mainly only a single substance (Pooni & Bansal, 2016). Unlike adults, childhood poisoning is usually accidental thus making it preventable with some simple and intelligent interventions (Budhathoki et al., 2009).

II- Intentional child toxicity: Intentional child toxicity may be suicidal or homicidal.

(a) Suicidal toxicity WHO defines suicide as "the act of deliberately killing oneself" and suicide attempt as "any non-fatal suicidal behavior and refers to intentional self-inflicted poisoning, injury or self-harm which may or may not have a fatal outcome" (Giner et al., 2016).

Suicidal behavior in the young population has long been recognized as a serious public health concern (Hawton et al., 2012b). It is almost always in older children and adolescents (Andiran & Sarikayalar, 2004). Suicide is among the major causes of youth mortality throughout the world (Patton et al., 2009). suicide still ranks as the 11th leading cause of death in children aged 5 to 11 years, with devastating consequences for families (Murphy et al., 2003). It may be a manifestation of insecurity, self-injury due to guilty feelings or attention seeking behavior (Trangadia et al., 2016). Psychiatric disorders and substance abuse, highly associated with suicidal behaviors. There are several theories regarding the relationship between suicidal behaviors and substance abuse, including: (1) The effects of acute intoxication lead to high-risk behavior; (2) substance abuse disorders in youthful suicide may be secondary to affective illnesses, such as depression and (3) as self-destructive behaviors, suicidal behaviors and substance abuse share common biological, behavioral, and environmental origins or result from common vulnerabilities (Wu et al., 2004).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Adolescents live stressful period during puberty as there are many physiological and emotional changes occur that make them more reliable to affect with minor events such as poor school performance, bullying in school, failed relationship, conflict with parents, emotional insecurity and associated psychological conditions (Bindu et al., 2014).

Medications commonly used for committing suicide followed by pesticides and household product (Mutlu et al., 2010). An adolescent's home and its surroundings was the most common location for the adolescents' suicides (Lahti et al., 2014).

(b) Homicidal toxicity: Child homicide is a rare, yet is a tragic, event that occurs at rates of 2.0 per 100,000 inhabitants globally (Cavanagh et al., 2005). It most commonly occurs in infants within the first two years in their life (Bonsignore et al., 2016). Homicidal child toxicity is not easily discovered. Child abuse by caregivers mostly occurs by administration of drugs with the purpose of calming or sedating children, it commonly occurs at home (Kintz et al., 2010). Homicidal toxicity may be due to psychological disturbance of caregivers such as Munchausen syndrome by proxy (MSBP), also known as fabricated or induced illness in a child by a caregiver, so that the proxy will receive medical care that gratifies the caregiver. The most common methods of inflicting harm are poisoning and suffocation (Flaherty & Macmillan, 2013).

Some caregavers using Alimemazine or trimeprazine that is a phenothiazine derivative related to chlorpromazine; it has the properties of antihistamines and it is not recommended for use in children less than 2 years old because of indications of highly variable pharmacokinetics, heavy hangovers as a commonly reported side effect, and a few reports of serious or fatal adverse reactions such as sever hyperpyrexia, neuroleptic malignant syndrome, respiratory depression, convulsions and sudden infant death (Gomila et al., 2016).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Important Medico-Legal Concepts

Children are the real wealth of nation, the future of humanity, the source of its strength, and the continuation of its populating the universe. Humanitarian society has several attempts in order to protect the child and to defend his rights through a variety of international, regional, and local conventions and documents especially with the spread of armed conflicts and wars (Balbakay, 2014).

Many children exposed to physical, verbal, or psychological violence, carelessness, discrimination and exploitation. Beside, many parents in every society, regardless of creed, origin, social and economic status, have indeed lost their children as a result of their own negligence. They are so careless about the places their children go to, the friends they associate with, the time they spend with no benefit, and so on. This negligence of such parents causes the children to grow up without any responsible adult and without caring guidance or supervision (Santoso, 2016).

Child neglect and maltreatment have a long-term impact on emotion processing abilities in adulthood, IQ and psychopathology (Young & Widom, 2014).

I. Medical Aspects: Role of the physician in acute child toxicity: The diagnosis of acute poisoning may be apparent from the clinical history. However, it should also be considered in patients who present with altered consciousness, those unable to give a history and those who present with an episode of deliberate self-harm. A focused toxicological physical examination should be performed on every poisoned patient. The toxicological physical examination seeks to identify a group of signs and symptoms that are reliably caused by a specific xenobiotic (Meredith, 1999). In cases where poisoning is suspected, but cannot be confirmed by clinical history, a detailed physical examination, including a full neurological assessment is an essential part of substance identification (Riordan et al., 2002).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Initially, assessment and treatment of the airway, breathing and circulation is mandatory. Treatment should first focus on supportive measures, including use of high-flow oxygen and intravenous fluids. Depression of the nervous system can occur and epileptic fits should be treated with intravenous benzodiazepines (Bradberry & Vale, 2003).

Role of investigations in identifying the poisons: A careful history may obviate the need for blood tests. Standard haematological investigations are rarely diagnostically helpful, although the prothrombin time may be prolonged after ingestion of anticoagulants or in case of hepatic damage (e.g. in paracetamol poisoning) (Riordan et al., 2002). Blood glucose estimation should be performed in all cases, as hypoglycaemia is typically caused by an overdose of insulin or oral hypoglycaemic agents and complicates ethanol intoxication, particularly in children (Vichova & Jahodar, 2003).

Detection of poisons in different sample is shown in Table (7) according to Poklis (2001).

Table (8): Shows methods used to analysis different poisons in different samples

GC : Gas chromatography, GC/MS : Gas chromatography/mass spectrometry, HPLC : High-pressure liquid chromatography, TLC : Thin-layer chromatography (Poklis, 2001)

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Radiology can be used to confirm ingestion of metallic objects or ingestion of elemental mercury or iron salts. An electrocardiogram (ECG) is of limited diagnostic value, although tachycardia with prolongation of the PR and/or QRS intervals in an unconscious patient should prompt consideration of tricyclic antidepressant overdose (Bradberry & Vale, 2003).

Postmortem examination if death occurs: According to Levine, (2003), History of the case as stated by police or relatives. History gives 2 or more vital points (1 how long the victim survived after initial symptoms. 2. any treatment given). Post-mortem examination, (a) External and (b) Internal Chemical analysis: detection of poison in the body fluids. Preservation of viscera and other material for lab examination.

(a) External Post-mortem examination: The surface of the body and clothes may show stains or marks of vomit, faeces or the poison itself. Dark brown stains over lips, cheeks, chin etc. Are suggestive of burning by corrosives. Smell from mouth and nose: compress the chest and inhale near nose. Substances which may have specific odour are alcohol, phenol, organophosphorus compound, etc. Color of postmortem staining: the skin may be deep blue In case of asphyxiant poisons and aniline. While, bright red or cherry red In case of CO and HCN poisonings (Levine, 2009). The natural orifices of the body may show the presence of poisonous material or the signs of its having been used. Deep cyanosis occurs with opium and cardiac poisons as aconite . Early rigor mortis is found with strychnine. Blood tinged froth from mouth and nose is common with organophosphorus compounds. Injection marks may be due to injection of poisons (snake bite or otherwise) or conceder as sign of treatment (Levine, 2003).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

(b) Internal Post-mortem examination: Smell: on opening the body notes any specific smell. It will be strongest in stomach. Mouth and throat examination for detection of any inflammation or erosion. Oesophagus: corrosives produce marked softening and desquamation of the mucous membrane (Richardson, 2000). Upper respiratory tract: examine for evidence of volatile or inhaled poison. Laryngeal edema occurs in barbiturates and alcohol poisoning. Lung: Voluminous, congested, presence of Tardieu's spots - In case of asphyxiants and inhaled poisons. Cut section gives blood stained frothy-fluid in case of opium and other asphyxiants (Drummer, 2004). Chest cavity -Smell of volatile poisons cyanogen, opium etc. can be detected. Stomach: hyperaemia in irritant poisons covered with viscid secretions showing hemorrhagic foci. The stomach mucosa shows softening of mucosa with excess mucous secretion in corrosives. Perforation in sulfuric acid poisoning. The stomach is black and extensively damaged (Raghavendra et al., 2017). Liver: become fatty yellow in phosphorus and ferrous sulphate. Necrosis is seen in chloroform. Kidneys: show degenerative changes with mercury, oxalic ad carbolic acid, phosphorus, cantharides, viper snake venom and many others. In case of oxalic acid poisoning, white powders of oxalate crystals are present in the tubules and the calyces (Leikin & Watson, 2003). Heart: Presence of subendocardial haemorrhagic spots is in cases of arsenic, phosphorus, mercuric chloride etc. Brain and spinal cord: Congestion and edema of brain and spinal cord are seen in cases of cerebral and spinal poison (e.g. strychnine). Brain may be congested. oedematous with occasional haemarrhagic points at places in cases of asphyxiant poisons (Poklis, 2001).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Collection of samples at autopsy for toxicological screening: Many factors may affect the result of screening as unsuitable sample (for example take urine instead of blood), inadequate amount, incorrect sample site and delayed or unsatisfactory storage and transport to laboratory (Drummer & Gerostamoulos, 2002).

Almost all baseline pharmacokinetics and plasma concentration monitoring have been undertaken on plasma samples collected from venous blood. Antemortem samples are extremely important in ascertaining a cause of death but unfortunately it rarely occur outside hospital. Forensic samples are usually blood collected from a femoral site, but at times, blood may be collected from central veins, the subclavian vein, or cardiac chambers in cases where femoral samples are unavailable. Blind stick collection of femoral samples are probably as reliable as samples obtained from a cut- down and ligated vein, which also allows samples to be collected prior to the formal autopsy (Hargrove & McCutcheon, 2008).

The use of whole blood complicates the interpretation of some results, where the blood/partition ratio is less or greater than one. Where blood/ partition ratio is the ratio of the concentration of drug in whole blood and plasma, to the concentration of drug in plasma. For example, phenytoin has a partition ratio of 0.5–0.6, and may in part, account for lower concentrations being found postmortem, while chloroquine concentrations are three to ten times that of plasma due to binding to platelets and granulocytes (May et al., 1999). Certain therapeutic compounds have a high degree of affinity for the red blood cell fraction of whole blood and have large RBC-to plasma concentration ratios (Kalamaridis & DiLoreto, 2014).

Urine samples are easy to collect and contain either parent drug or metabolite(s). Collection of gastric contents will give information and to very recent ingestion of drug, vitreous humor is of particular value in cases involving alcohol. To ensure the chemical stability of the drug is maintained,

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects it is essential that correct collection procedures be used for collection, transport, and short- and long-term storage of samples (Drummer & Gerostamoulos, 2002).

Collection of biological specimens at autopsy: According to Dinis-Oliveira et al., (2010), Stomach and its content: open along lesser curvature then examine wall for fragments of adherent poisons, measure content, look for tablets and capsules and preserve whole content if small amount; if there is a large amount, take an aliquot. Upper part of small intestine and its content. Liver: 100-200 gm. Kidney: 50-gm from each one. Spleen: small part. Blood: 30-100ml. Urine: 30-100ml.

Samples of solid organs such as brain, adipose tissue, hair, and bone may be collected under special circumstances (Drummer & Gerostamoulos, 2002).

Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample (Dinis-Oliveira et al., 2010)

Special considerations: According to Flanagan et al., (2005), Narcotic poisons: collect bile and one half of one lung.

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Inhalation poisons: (a) Tie trachea, (b) collect bronchial air, (c) collect lung and put it in air tight container as nylon bags without any preservation. Pesticide: fatty tissue from abdominal wall, perinephric region and brain. Heavy metal: hair, nails and bones. Alcohol: vitreous humor.

Preservatives used: According to Riordan et al., (2002), For Viscera: absolute alcohol or rectified spirit. Exception: alcohol, chloroform, chloral hydrate, formaldehyde, ether, phosphorus (alcohol prevents the luminosity of phosphorus in dark) etc. Blood should be preserved in fluoride, oxalate, E.D.T.A., gold chloride or citrate. Urine and clothes: without any preservative.

Analysis of specimens: There is little to differentiate analytical procedures used in other branches of forensic toxicology from those used in postmortem investigations. The same quality standards as established for the analysis of specimens derived from living individuals also apply to postmortem specimens (Skopp, 2004).

Analytical methods can be broadly classified into three types: screening procedures, confirmation procedures and specific methods. Screening for volatiles by gas chromatography (GC) is recommended, and immunoassays for common drugs of abuse are regularly included in a toxicology investigation. Interaction with putrefactive amines is commonly seen in immunoassays for amphetamine type drugs; and ambroxol was reported to show some cross reactivity in immunoassays for LSD. If death occurs within a very short time after drug administration an insufficient concentration may be present in urine to give a positive result (Drummer, 2007).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Additionally, comprehensive chromatographic screens for basic, neutral and acidic drugs using UV- or mass spectrometric (MS) detection are required. Screening methods based on MS data will provide confirmation of a suspected compound. The particular compound should also be detected in at least one other specimen. The second method may use a different detection mode or an entirely different procedure (McGrath & Jenkins, 2009).

Numerous procedures exist that quantify specific drugs, especially by GC/MS or liquid chromatography (LC) /MS, with LC/MS becoming a gold standard for detection of very low drug concentrations (Maurer, 2007).

II. Legal Aspects Definitions of childhood: a. Scientific definition: Childhood is the age span ranging from birth to adolescence. In developmental psychology, childhood is divided according to the developmental stages up into newborn from birth to 1 yr, toddler hood (learning to walk) from 1 to 3 yrs, early childhood (play age) from 3 to 8 yrs, middle childhood (school age) from 8 till puberty, and adolescence (puberty through post-puberty) from the onset of puberty to 18 yrs (Shaffer & Kipp, 2013).

b. Islamic definition: A child is a human being from the moment he became a fetus in his mother's womb until puberty. If signs of puberty don’t appear a person remains a child until the age of 15 years (Taheri & Fard, 2015).

c. Legal definition: A child is someone who has not reached physical and mental development necessary for social life considered in terms of age (Taheri & Fard, 2015).

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

According to Egyptian Child Law no. 12 of 1996 and amended by Law No. 126 of 2008 article no. 2 (Appendix 1): the child in the field of care provided in this Law shall mean any person who has not attained the age of 18 years Full Calendar Year.

Definition of negligence: Scientific definition: negligence is the pattern of failure of caregiver to provide for the development and wellbeing of the child. In one or more of the following areas: Health, Education, Emotional development, Nutrition, and Shelter and safe living conditions (Butchart & Finney, 2006).

Child neglect penalty: According to Egyptian Child Law No. 12 of 1996 and amended by Law No. 126 of 2008 article No 96 (Appendix 1): each one who expose the child to any risk conditions will be punished by imprisonment for a period of not less than six months and a fine of not less than two thousand pounds and not exceeding five thousand pounds or One of these two punishments.

Articles No 97, 98 and 99 in the Egyptian child law explain how General Committee for the Protection of Children works to detect and protect any child exposed to any risk condition (see appendix1).

General Committee for the Protection of Children: Each governorate has a general committee for the protection of children, headed by the governor and the membership of directors of security departments, social and health affairs and a representative of civil society organizations concerned with children's affairs

REVIEW OF LITERATURE

Chapter III: Manner of Pediatric Toxicity & Other Medicolegal Aspects

Function: This committee is responsible for: Formulating the general policy for the protection of children in the governorate and following up the implementation of these policies. Forming of a subcommittee on the protection of children within the department or police station.

Subcommittee on the protection of children: Its composition that includes security, social, psychological, medical and educational. The number of its members shall not less than five and not exceed seven members, including the President. The Committee may include among its members one or more representatives of civil society organizations concerned with children's affairs.

Function: Responsible for monitoring all exposures and preventive intervention And the necessary treatment for all such cases and follow-up action.

The penalty for suicidal attempt and suicide: In the Islamic faith, suicide is condemned and forbidden. It is believed that those who kill themselves will end up in hell (Mesbah, 2014).

According to article No 45 of Egyptian penal law: Attempt is beginning to carry out a deed with the intent of committing a felony or misdemeanor if the effect of such deed is stalled or failed for reasons beyond the will of the doer. The mere resolution or preparatives to commit shall not be considered an attempted felony or misdemeanor.

So the suicide or attempt of suicide are not considered a crime and there is not any penalty on it as no penalty on dead person.

SUBJECTS & METHODS

SUBJECTS AND METHODS

SUBJECTS: This is a prospective cross sectional study conducted on 152 cases of pediatric age group (under 18 years old) presented and admitted to NECTR (National Environmental and Clinical Toxicological Research Center) during 6 months (period of study ) with a proper history of acute toxicity or without proper history but with symptoms and signs suggesting acute toxicity whatever the manner of toxicity.

The Ethical committee of Forensic and Clinical Toxicology Department in Al Kasr Al-Aini Medical School approved the study design.

Patients were classified into 2 groups according to manner of toxicity: Group 1: Unintentional (accidental) toxicity. Group 2: Intentional (suicidal) toxicity.

The participants were classified into 4 groups depending on their age, according to Zisowsky et al., (2010): Group A: Infant and toddler (28 days to <3 yrs.). Group B: Early childhood (3 yrs. to< 9 yrs.). Group C: Late childhood (9 yrs. to <13 yrs.). Group D: Adolescent (13 to <18 years).

Patients' Inclusion Criteria: Patients aged below 18 yrs. Both sexes. Cases presented to NECTR during period of the study (6 months). Patients with history of consumption of poison with significant signs and symptoms who presented with or without the taken poison. Patients with doubtful history of consumption of poison but with definite signs and symptoms of acute poisoning.

SUBJECTS & METHODS

Recurrent poisoning. Bites of any poisonous creature. Chemical food poisoning.

Patients' Exclusion Criteria: Patients aged ≥ 18yrs. Viral and bacterial Food poisoning. Idiosyncratic reaction of drugs.

METHODS: Cases were analyzed with respect to: Demographic data of the patients: age, sex, residence, level of education and family status. Primary data for assessment of the patient that include: o Manner of toxicity. o Type of poison and its availability to the child o Place of exposure. o Amount and form of poison. o Duration between exposure and presentation. o The first aid that may be done to the patient. o Associated morbidity. o History of medications o History of psychiatric diseases Data concerning physical examination and investigations done to the patient according to the different poisons: o CNS manifestation: alert, drowsy, coma, convulsion or hallucination. o Vital signs: normal, affected or shocked. o Investigations: routine investigation, done or not and specific investigation, done or not.

SUBJECTS & METHODS

Severity and mortality rate of each poisons detected by poison severity scoring (PSS) and the acute physiology and chronic health evaluation (APACHE II) (Sam et al., 2009).

Table (9): APACHE II scoring system according to acute physiology and chronic health diseases

(Sam et al., 2009)

SUBJECTS & METHODS

Table (10): Poison scoring system (PSS) according to signs and symptoms

(Pach et al., 1999)

SUBJECTS & METHODS

Data regarding lines of treatment: o Methods GIT decontamination: no decontamination done, gastric lavage with activated charcoal or activated charcoal only. o Symptomatic treatment: not done, given at home or given in hospital. o Antidote: the drug has no specific antidote and only supportive treatment was given. Treatment was given in full regimen, or given but the patient improved before full regimen was completed. The patient not admitted and no need to antidote.

Outcome of the case: Improved and discharge, discharge on his or her parent responsibility, died, complicated or the drug with no toxic effect.

Admission: Admitted cases including patient admitted to ICU or observed to certain period or not admitted.

Limitations of Resources: Laboratory investigation not always available. Not all the cases gave all needed informations or proper informations for fear of any responsibility. Not all the antidotes available in our center.

STATISTICAL ANALYSIS: Data were coded and entered using the statistical package SPSS (Statistical Package for the Social Sciences) version 24. Data was summarized using mean, standard deviation, median, minimum and maximum in quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Comparisons between quantitative variables were done using the non-parametric Kruskal-Wallis and Mann-Whitney tests (Chan, 2003a). For comparing categorical data, Chi square (χ2) test was performed.

SUBJECTS & METHODS

Exact test was used instead when the expected frequency is less than 5 (Chan, 2003b). Correlations between quantitative variables were done using Spearman correlation coefficient (Chan, 2003c). p-values less than 0.05 were considered as statistically significant.

RESULTS

The sample in the present study included 152 participants, categorized according to manner of toxicity as in Fig. (8).

Fig. (8): Distribution of the cases in the present study according to manner of toxicity

Admission:

Fig. (9): Pie chart shows percentage distribution according to admission

Figure (9) shows that majority of cases were admitted (78.3%).

RESULTS

Treatment:

Fig. (10): Bar chart shows percentage of Management of cases

Figure (10) shows that most cases took charcoal only (50.7%). Cases with available specific antidote were 19.7% of cases.

Final outcome:

Fig. (11): Bar chart percentage distribution of cases according to final outcome

Figure (11) shows that 52.6% of cases improved and discharged, while 3.3% of cases complicated.

RESULTS

I. SOCIO‐DEMOGRAPHIC STUDY

(a) Age:

Fig. (12): Pie chart showing percentage distribution according to age

Regarding ages in the present study, Fig. (12) Shows that the majority of cases were toddlers (44%) followed by (adolescents), (early childhood) and (late childhood). The relation between age and manner of toxicity: Table (8) shows significant relations between them (p<0.001). Suicidal toxicity (group 2) was common at late childhood & adolescence, while accidental toxicity (group 1) was common at toddler & early childhood.

Table (11): Distribution of cases according to age and manner of toxicity

Group (1) Accidental Group (2) Suicidal toxicity toxicity p-value Count % Count % Toddler (1-3 yrs.) 67 75.3% 0 0.0% Early childhood (3-9 yrs.) 22 24.7% 0 0.0% <0.001* Late childhood (9-13 yrs.) 0 0.0% 10 15.9% Adolescence (13-18 yrs.) 0 0.0% 53 84.1%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

The relation between ages and the type & amount of poison: Table (12) shows a significant relation (p0.004) between age in group 1 (accidental cases) and different type and amount of poison. On the other hand, Table (13) shows no significant relation (p 0.140) between age in group 2 (suicidal cases) and type and amount of poison.

Table (12): Relation between age in group 1 and type of poison and its amount

Group 1 Early p- Toddlers childhood value Count % Count %

Drug abuse 14 20.9% 1 4.5% Household 22 32.8% 3 13.6% Main types of poison Medication 24 35.8% 15 68.2% 0.004* Pesticide 7 10.4% 1 4.5% Snake bite 0 0.0% 2 9.1% Unknown amount 38 56.7% 6 27.3%

Below toxic dose 3 4.5% 4 18.2% Amount of

poison Just the toxic dose 8 11.9% 7 31.8% 0.023* Above the toxic dose 6 9.0% 2 9.1% Not toxic 12 17.9% 3 13.6%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Table (13): Relation between age in group 2 and type of poison and its amount

Group 2 age groups Late p- Adolescent childhood value Count % Count % Drug abuse 1 10.0% 1 1.9% Household 0 0.0% 1 1.9% Main types of 0.140 poison Medication 8 80.0% 31 58.5% Pesticide 1 10.0% 20 37.7% Snake bite 0 0.0% 0 .0% Unknown amount 2 20.0% 3 5.7% Blew toxic dose 0 0.0% 2 3.8% Amount of poison Just the toxic dose 0 0.0% 8 15.1% 0.185 Above the toxic dose 6 60.0% 36 67.9% Not toxic 2 20.0% 4 7.5%

Chi square (χ2) test *p-value >0.05 is statistically insignificant

RESULTS

The relation between age and availability of poison: Table (14) shows significant relation (p<0.001) between them in group 1. On the other hand, Table (15) shows no significant relation (p 0.094) between age in group 2 and availability of poison.

Table (14): Relation between age in group 1 and availability of poison

Group (1) Early p- Availability of poison Toddlers childhood value Count % Count % Accessible surface 41 61.2% 3 13.6% Open cupboard 19 28.4% 8 36.4% Familiar bottle 5 7.5% 1 4.5% Mother or father medication 0 0.0% 6 27.3% Buy it 0 0.0% 0 0.0% <0.001* Used or present at work 0 0.0% 1 4.5% Used at home and children able to 2 3.0% 2 9.1% get it Patient’s medication 0 0.0% 0 0.0% Inhabitant in surrounding 0 0.0% 1 4.5% environment

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Table (15): Relation between age in group 2 and availability of poison

Group (2) Availability of poison Late childhood Adolescent p-value Count % Count % Accessible surface 0 0.0% 0 0.0% Open cupboard 0 0.0% 0 0.0% Familiar bottle 0 0.0% 0 0.0% Mother or father medication 7 70.0% 22 41.5% Buy it 0 0.0% 5 9.4% 0.094 Used or present at work 1 10.0% 3 5.7% Used at home and the patient 1 10.0% 22 41.5% able to get it Patients medication 1 10.0% 1 1.9% Inhabitant in surrounding 0 0.0% 0 0.0% environment

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

The relation between age and most probable cause: Table (16) shows significant relation (p<0.001) between them in group 1 the most probable cause of accidental toxicity in of toddlers is negligence. In group 2 (suicidal cases), table (17): shows no significant relation (p 0.346) between age in group 2 and the most probable cause.

Table (16): Relation between age in group 1 and the most probable cause

Group 1 age groups The most probable cause Toddlers Early childhood p-value Count % Count % Negligence 62 92.5% 5 22.7% Over curiosity 5 7.5% 12 44.5% Family problem 0 0.0% 0 0.0% Psychological disturbance 0 0.0% 0 0.0% <0.001* School problem 0 0.0% 0 0.0% Emotional disturbance 0 0.0% 0 0.0% Wrong medication 0 0.0% 5 22.7%

Chi square (χ2) test *p-value <0.05 is statistically significant

Table (17): Relation between age in group 2 and the most probable cause

Group 2 age groups The most probable cause Late childhood Adolescent p-value Count % Count % Negligence 0 0.0% 0 0.0% Over curiosity 0 0.0% 0 0.0% Family problem 7 70.0% 37 69.8% Psychological disturbance 1 10.0% 5 9.4% 0.346 School problem 2 20.0% 8 15.1% Emotional disturbance 0 0.0% 3 5.7% Wrong medication 0 0.0% 0 0.0%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

No significant relations between ages and location of exposure or previous attempts in both group 1 & group 2 (Tables 18 & 19) as p- value equal one in both relations.

Table (18): Relation between age in group 1 and (location of exposure and previous attempts)

Group 1 Toddlers Early childhood p-value Count % Count % Location of Home 58 86.6% 19 86.4% 1 exposure Outside home 9 13.4% 3 13.6% No 65 97.0% 22 100.0% Previous Single time 1 1.5% 0 0.0% 1 attempts Twice 1 1.5% 0 0.0% Three times 0 0.0% 0 0.0%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

Table (19): Relation between age in group 2 and (location of exposure and previous attempts)

Group 2

Late childhood Adolescent p-value Count % Count % Location of Home 9 90.0% 50 94.3% 0.508 exposure Outside home 1 10.0% 3 5.7% No 9 90.0% 46 86.8% Previous Single time 1 10.0% 3 5.7% 0.771 attempts Twice 0 0.0% 3 5.7% Three times 0 .0% 1 1.9%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

(B) Sex:

Sex

36.8%

63.2%

male female

Fig. (13): Pie chart showing percentage distribution according to sex

Concerning sex in the current study, Fig. (13) shows that females represented the majority of studied cases (63.2%).

87.30%

53.90% 46.10%

12.70%

accidental toxicity suicida l tox icity male female

Fig. (14): Bar chart shows percentage distribution of cases according to sex and manner of toxicity

The relation between sex and manner of toxicity (2 groups), Fig. (14): Shows significant relation (p<0.001) between them most of the cases in accidental toxicity were males and most of cases in suicidal toxicity were females.

RESULTS

Relation between sex and (type of poison and its amount): Table (20) shows significant relation (p 0.004) (p 0.015) respectively between sex and (type of poison and its amount) as most of females took medication and house hold, while most of males took medications. Relation between relation between sex and the most probable cause: Table (21) shows significant relation (p<0.001) between them, as the most common cause of toxicity in males was neglect, while the most probable cause of toxicity in females was family problems followed with neglect.

Table (20): Relation between sex and (type of poison and its amount)

Sex Male Female p-value Count % Count % Drug abuse 6 10.7% 11 11.5% Household 17 30.4% 9 9.4% Main types of 0.004* poison Medication 23 41.1% 55 57.3% Pesticide 8 14.3% 21 21.9% Snake bite 2 3.6% 0 .0% Unknown amount 25 44.6% 24 25.0% Below toxic dose 5 8.9% 4 4.2% Amount of 0.015* poison Just the toxic dose 8 14.3% 15 15.6% Above the toxic dose 10 17.9% 40 41.7% Not toxic 8 14.3% 13 13.5%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Table (21): Relation between sex and most probable cause

Sex Most probable cause Male Female p-value Count % Count % Neglect 37 66.1% 31 32.3% Over curiosity 10 17.8% 7 7.2% Family problem 7 12.5% 37 38.5% Psychological disturbance 0 0.0% 6 6.2% <0.001* School problem 1 1.8% 8 8.3% Emotional disturbance 0 0.0% 3 3.1% Wrong medication 1 1.8% 4 4.2%

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between sex and previous attempts: Table (22) shows no significant relation (p 0.845) between them.

Table (22): Relation between sex and previous attempts

Sex Previous attempts Male Female p-value Count % Count % No 54 96.4% 88 91.7%

Single time 1 1.8% 4 4.2% 0.845 Twice 1 1.8% 3 3.1% Three times 0 0.0% 1 1.0%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

Fig. (15): Pie chart showing percentage distribution according to residence

Residence distribution in the present study: Fig. (15) shows that majority of cases came from rural area.

60.70% ru ral urban 60.30%

39.30% 39.70%

ac cident al toxicity suicidal toxicity

Fig. (16): Bar chart relation between residence and manner of toxicity

Relation between residence and manner of toxicity (2 groups): Fig. (16) shows significant relation (p 0.004) between them that most of accidental cases came from rural area, while most of suicidal cases came from urban area.

RESULTS

Relation between residence and type of poison: Table (23) shows significant relation (p<0.001) between them as most of rural cases took pesticide, while most of urban cases took medications. Relation between residence and 1st aid: Table (24) shows significant relation (p<0.001) between them, as most of 1st aid was done in wrong way in rural case.

Table (23): Relation between residence and type of poison

Residence Main types of poison Rural Urban p- value Count % Count % Drug abuse 12 15.2% 5 6.8% Household 22 27.8% 4 5.5% Medication 16 20.3% 62 84.9% <0.001* Pesticide 27 34.2% 2 2.7% Snake bite 2 2.5% 0 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Table (24): Relation between residence and 1st aid

Residence st 1 id Rural Urban p-value Count % Count % Not done 34 43.0% 61 83.6% Done in good way 1 1.3% 3 4.1% <0.001* Done in wrong way 44 55.7% 9 12.3%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Relation between residence and availability of poison: Table (25) shows significant relations (p<0.001), as most of rural cases got poison from low surface, while most of urban cases got poison as it was their parents medications.

Table (25): Relation between residence and availability of poison

Residence Availability of poison Rural Urban p-value Count % Count % Accessible surface 38 48.1% 6 8.2% Open board 8 10.1% 19 26.0% Familiar bottle 4 5.1% 2 2.7% Mother or father medication 7 8.9% 28 38.4%

Buy it 1 1.3% 4 5.5% <0.001* Used or present at work 4 5.1% 1 1.4% Used at home and the patient 16 20.3% 11 15.1% able to get it Patient’s medication 0 0.0% 2 2.7% Common in surrounding 1 1.3% 0 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Relation between residence and the most probable cause of toxicity: Table (26) shows significant relations (p 0.004) between them, as the cause among rural cases it was negligence while among urban cases was family problems followed with neglect. Relation between residence and hours of delay: Table (27) shows a significant relation (p<0.001) between them, Where majority of cases of toxicity occurred at home represented 89.5%, while outside home represented 10.5%.

Table (26): Relation between residence and the most probable cause of toxicity

Residence p- Most probable cause of toxicity Rural Urban value Count % Count % Negligence 46 58.2% 22 30.1% Over curiosity 7 8.9% 10 13.6% Family problem 20 25.3% 24 32.9% Psychological disturbance 3 3.8% 3 4.1% 0.004* School problem 1 1.3% 8 11.0% Emotional disturbance 1 1.3% 2 2.7% Wrong medication 1 1.3% 4 5.5%

Chi square (χ2) test *p-value <0.05 is statistically significant

Table (27): Relation between residence and hours of delay

Residence

p- Rural Urban value

Delay in Mean ±SD Median Minimum Maximum Mean ±SD Median Minimum Maximum hrs. 3.20 .98 3.00 1.00 6.00 2.50 1.92 2.00 1.00 12.00 <0.001

Non-parametric Mann-Whitney test *p-value <0.05 is statistically significant

RESULTS

(D) Educational level:

Educational Level

Preschool primar y preparatory secondary not educated

21.7%

15.8% 52. 6%

7.9%

Fig. (17): Pie chart shows percentage distribution of the cases according to their educational level

Regarding to educational level in the present study, Fig. (17) shows that the majority of cases in present study was preschool (nursery age) representing followed by secondary school, preparatory, primary and not educated.

preschool age 89.90% primary preparatory secondary 52.40% not educated 36.50%

7.90% 7.90% 1.10% 0.00% 1.10% 0.00% 3.20%

accidental toxicity suicidal toxicity

Fig. (18): Bar chart showing percentage distribution of cases according to manner of toxicity and their educational level

Regarding to manner of toxicity and educational level of the patients, Fig. (18) shows that most of accidental cases is preschool age, while most of suicidal cases (group 2) is in secondary school followed with preparatory.

RESULTS

Relation between educational level and type of poison: Table (28) shows significant relations (p<0.001) between them as medication common poison among preschool, while pesticide was common poison among non-educated cases.

Relation between educational level and amount of poison: Table (29) shows significant relations (p<0.001) between them as most of preschool and non-educated cases took unknown amount of toxin.

Relation between educational level and the most probable cause of toxicity: Table (30) shows significant relations (p<0.001) between them as the most probable cause in preschool cases was neglect.

RESULTS

Table (28): Relation between educational level and type of poison

Education Main types of poison Preschool age Primary Preparatory Secondary Not educated p-value Count % Count % Count % Count % Count % Drug abuse 15 18.8% 0 0.0% 2 8.3% 0 0.0% 0 0.0% Household 25 31.2% 0 0.0% 1 4.2% 0 0.0% 0 0.0% Medication 33 41.2% 8 66.7% 14 58.3% 23 69.7% 0 0.0% <0.001* Pesticide 7 8.8% 4 33.3% 6 25.0% 10 30.3% 2 66.7% Snake bite 0 .0% 0 0.0% 1 4.2% 0 0.0% 1 33.3%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Table (29): Relation between educational level and amount of poison

Education level Amount of poison Preschool age Primary Preparatory Secondary Not educated p-value Count % Count % Count % Count % Count % Unknown amount 42 52.5% 0 0.0% 2 8.3% 3 9.1% 2 66.7% Blew toxic dose 5 6.2% 2 16.7% 0 .0% 2 6.1% 0 0.0%

Just the toxic dose 11 13.8% 5 41.7% 3 12.5% 4 12.1% 0 0.0% <0.001* Above the toxic 7 8.8% 5 41.7% 14 58.3% 23 69.7% 1 33.3% dose Not toxic 15 18.8% 0 0.0% 5 20.8% 1 3.0% 0 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

Table (30): Relation between educational level and the most probable cause of toxicity

Education Most probable cause Preschool age Primary Preparatory Secondary Not educated p-value Count % Count % Count % Count % Count % Negligence 66 82.5% 2 16.7% 0 0.0% 0 0.0% 0 0.0% Over curiosity 14 17.4% 1 8.3% 1 4.2% 0 0.0% 1 33.3% Family problem 0 0.0% 3 25.0% 17 70.8% 22 66.7% 2 66.7% Psychological disturbance 0 0.0% 0 0.0% 3 12.5% 3 9.1% 0 0.0% <0.001* School problem 0 0.0% 0 0.0% 2 8.3% 7 21.2% 0 0.0% Emotional disturbance 0 0.0% 1 8.3% 1 4.2% 1 3.0% 0 0.0% Wrong medication 0 0.0% 5 41.7% 0 0.0% 0 0.0% 0 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

RESULTS

(E) Father and mother work and their educational level:

31.60% no t working and no t educate d 27.00%wo rki ng and not educat ed

wo rki ng and low 19.70% education wo rki ng and high 16.40% education wo rki ng and moderat e education

2 .60% 2.60 %

Fig. (19): Bar chart shows percentage distribution of the cases according to father work and education

Distribution of the cases according to father work and education: Fig. (19) shows that most of cases exposed to toxicity the father was working and not educated followed by working and moderate education.

46.70% housewife and no t educate d housewife and educa te d working no t educated working and moderate educatio 23.00% working and high education 20 .40% died

3.90% 5.90 % 2.60%

Fig. (20): Bar chart shows percentage distribution of the cases according to mother work and education in percentage

RESULTS

Distribution of the cases according to mother work and education: Fig. (20) shows that most of cases exposed to toxicity the mother was housewife and not educated followed by housewife and educated.

39.30% not working and not educated working and not educated 30.20% working and low education 24.70% 25.40% working and high education 19.10% 20.60% 15.70% working and moderate education 12.70%died 6.30% 4.80% 1.10% 0.00%

accide ntal toxicity suicidal toxicity

Fig. (21): Bar chart shows percentage distribution of cases according to father work and education and manner of toxicity

Distribution of cases according to father work and education and manner of toxicity (2 groups): Fig. (21) shows that most of accidental cases their fathers were working and not educated, while most of suicidal cases their fathers were working and moderate education.

57.30% not working and not educated housewife and not educated 31.70% housewife31.70% and educated 23.80% 22.50% working not educated 12.40% 5.60% working6.30% and moderate6.30% educatio 1.10% 2.20% 4.80% working and high education accidental toxicity suicidal toxicity

Fig. (22): Bar chart shows percentage distribution of cases according to mother work and education and manner of toxicity

RESULTS

Distribution of cases according to mother work and education and manner of toxicity (2 groups): Fig. (22) shows that most of accidental cases the mother was housewife and not educated, while most of suicidal cases mothers were (housewife and not educated) and (working and moderate educated) both of them represented.

Relation between mother work and education and the availability of poison: Table (31) shows significant relations (p<0.001) between them as cases of mother (working and high educated) and (working and moderate educated) took their parents’ medications, while most housewife and not educated mother’s cases took toxins at low surface.

RESULTS

Table (31): Relation between mother work and education and the availability of poison

Mother work & education

Availability of poison Housewife Housewife Working Not Working mod. Working High p-value Not educated educated educated education Edu. Count % Count % Count % Count % Count % Accessible surface 35 49.3% 8 22.9% 1 16.7% 0 0.0% 0 0.0% Open cupboard 9 12.7% 5 14.3% 1 16.7% 10 32.3% 2 22.2 Familiar bottle 3 4.2% 3 8.6% 0 0.0% 0 0.0% 0 0.0% Mother or father medication 8 11.3% 8 22.9% 1 16.7% 15 48.4% 3 33.3

Buy it 0 0.0% 2 5.7% 0 0.0% 3 9.7% 0 0.0% <0.001* Used or present at work 3 4.2% 0 0.0% 2 33.3% 0 0.0% 0 0.0% At home and pt able to get it 12 16.9% 9 25.7% 1 16.7% 3 9.7% 2 22.2 Pt’s medication 0 .0% 0 0.0% 0 0.0% 0 0.0% 2 22.2 Inhabitant in surrounding 1 1.4% 0 0.0% 0 0.0% 0 0.0% 0 0.0% environment

Chi square (χ2) test p‐value ≥0.05 is stascally insigniﬁcant

RESULTS

Relation between father work and education and previous attempts: Table (32) shows no significant relation (p 0.310) between them. The same, regarding the results of the relation between mother work and education and previous attempts as Table (33) shows no significant relation (p0.288).

RESULTS

Table (32): Relation father work and education and (previous attempts)

Father work & education Working and Not working and Working and Working and Working and Previous attempts moderate Died not educated not educated low education high education P- education value Count % Count % Count % Count % Count % Count % No 4 100.0% 44 91.7% 24 96.0% 28 93.3% 39 95.1% 3 75.0% Single time 0 0.0% 1 2.1% 1 4.0% 1 3.3% 2 4.9% 0 0.0% 0.301 Twice 0 0.0% 3 6.2% 0 0.0% 1 3.3% 0 0.0% 0 0.0% Three times 0 0.0% 0 0.0% 0 0.0% 0 0.0% 0 0.0% 1 25.0%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

Table (33): Relation mother work and education and (previous attempts)

Mother work & education Working and Housewife and Housewife and Working not Working and high Previous attempts moderate not educated educated educated education p- education value Count % Count % Count % Count % Count % No 67 94.4% 31 88.6% 6 100.0% 30 96.8% 8 88.9% Single time 1 1.4% 3 8.6% 0 0.0% 0 .0% 1 11.1% 0.288 Twice 3 4.2% 1 2.9% 0 0.0% 0 .0% 0 0.0%

Three times 0 0.0% 0 0.0% 0 0.0% 1 3.2% 0 0.0%

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

RESULTS

Relation between father work and education and most probable cause of toxicity: Table (34) shows significant relations (p 0.001) between them as most cases of working and not educated or low education negligence was the most probable cause of toxicity.

Relation mother work and education and most probable cause of toxicity: Table (35) shows significant relations (p 0.002) between them as most cases of housewife and not educated or educated and working even with high education the neglect was the most probable cause of toxicity.

RESULTS

Table (34): Relation father work and education and (most probable cause of toxicity)

Father work & education Not working Working and Working and Working and Working and Most probable cause and not low high moderate Died p- not educated educated education education education value Count % Count % Count % Count % Count % Count % Negligence 0 0.0% 28 58.3% 17 68.0% 9 30.0% 14 34.1% 0 0.0% Over curiosity 1 25.0% 7 14.5% 0 0.0% 3 10% 6 14.6% 0 0.0% Family problem 2 50.0% 11 22.9% 7 28.0% 7 23.3% 16 39.0% 1 25.0% Psychological disturbance 0 0.0% 2 4.2% 0 0.0% 3 10.0% 0 0.0% 1 25.0% 0.001* School problem 0 0.0% 0 0.0% 1 4.0% 4 13.3% 2 4.9% 2 50.0% Emotional disturbance 1 25.0% 0 0.0% 0 0.0% 1 3.3% 1 2.4% 0 0.0% Wrong medication 0 0.0% 0 0.0% 0 0.0% 3 10.0% 2 4.9% 0 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

100

RESULTS

Table (35): Relation mother work and education and (most probable cause of toxicity)

Mother work & education Working and Housewife and Housewife and Working not Working and Most probable cause moderate not educated educated educated high education education p-value Count % Count % Count % Count % Count % Negligence 44 62.0% 14 40.0% 1 16.7% 5 16.1% 4 44.4% Over curiosity 7 9.8% 4 11.4% 1 16.7% 5 16.1% 0 0.0% Family problem 17 23.9% 13 37.1% 3 50.0% 10 32.3% 1 11.1% Psychological disturbance 2 2.8% 1 2.9% 0 0.0% 2 6.5% 1 11.1% 0.002* School problem 1 1.4% 1 2.9% 0 0.0% 6 19.4% 1 11.1% Emotional disturbance 0 0.0% 0 0.0% 1 16.7% 2 6.5% 0 0.0% Wrong medication 0 0.0% 2 5.7% 0 0.0% 1 3.2% 2 22.2%

Chi square (χ2) test *p-value <0.05 is statistically significant

101

RESULTS

Relation between father work and education and (hours of delay): Table (36) shows significant relation (p <0.001) between them .

Table (36): Relation between father work and education and (hours of delay)

Father work & education Delay in Not Working Working Working Working hrs. working and and not and low and high Died p-value and not moderate educated education education educated education Mean 3.62 3.05 2.94 2.02 3.06 3.75

± SD 1.25 1.03 0.88 1.07 2.05 4.19

Median 3.75 3.00 3.00 2.00 2.00 2.00 <0.001* Minimum 2.00 1.00 1.00 1.00 1.00 1.00 Maximum 5.00 6.00 4.00 6.00 12.00 10.00

Non-parametric Kruskal-Wallis test ± SD = Standard Deviation *p-value <0.05 is statistically significant

Fig. (23): Correlation between father work and education and (hours of delay)

Fig. (23) show positive correlation between father work and education and (hours of delay).

102

RESULTS

Relation between mother work and education and (hours of delay): Table (37) shows significant relation (p 0.007) between them.

Table (37): Relation between mother work and education and (hours of delay)

Mother work & education Delay in Housewife Housewife Housewife Housewife Housewife Housewife p- hrs. and not and not and not and not and not and not value educated educated educated educated educated educated Mean 3.00 2.69 3.08 3.00 1.89 3.00 ± SD 095 1.35 1.43 2.60 .93 095 Median 3.00 2.00 3.25 2.00 2.00 3.00 0.007* Minimum 1.00 1.00 1.00 1.00 1.00 1.00 Maximum 6.00 8.00 5.00 12.00 4.00 6.00

Non-parametric Kruskal-Wallis test ± SD = Standard Deviation *p-value <0.05 is statistically significant

Fig. (24) : Correlation between mother work and education and (hours of delay)

Fig. (24) show positive correlation between father work and education and (hours of delay).

103

RESULTS

II. DATA OF TOXICITY

(A) Poisons used in both studied groups: Regarding to availability of poison, Table (38) shows that most available poisons were on low surface (28.9%) followed by father and mothers medication (23%).

Table (38): Showing percentage of availability of poisons

Availability of Poisons Count % Accessible surface 44 28.9% Open cupboard 27 17.8% Familiar bottle 6 3.9% Mother or father medication 35 23.0% Buy it 5 3.3% Used or present at work 5 3.3% Used at home and anyone able to get it 27 17.8% Patient’s medication 2 1.3% Inhabitant in surrounding environment 1 0.7%

drug abuse household me d ica ti on pesticide snake bi te

19% 11 %

17%

52 %

Fig. (25): Pie chart shows percentage distribution of the cases according to common type of poison

104

RESULTS

Distribution of the cases according to common type of poison: Fig. (25) shows that most cases poisoned with medication (52%) followed by pesticide (19%).

unkown amount bl e w toxic dose just the toxic dose above the toxic dose not toxic 14%

32% 33%

15% 6%

Fig. (26): Pie chart shows percentage distribution of the cases according to amount of poison

Distribution of the cases according to amount of poison: Fig. (26) shows that most cases ingested above the toxic dose of poison (33%) followed by unknown amount (32%).

Fig. (27): Bar chart shows percentage distribution of the cases according to manner of toxicity and common type of poison

Distribution of the cases according to manner of toxicity in both studied groups and common type of poison: Fig. (27) shows that in group 1 (accidental cases) (43.8%), while in group 2 (suicidal cases) was (61.9%) took medications.

105

RESULTS

The relation between type of poison and its availability: Table (39) shows significant relations (p<0.001) between them. Drug of abuse & household products were at low surface, while parents’ medications and most of pesticide were available at home and patients able to reach it.

Table (39): Relation between type of poison and its availability

Main types of poison Availability of poison Drug Snake p-value Household Medication Pesticide abuse bite Accessible Count 14 20 3 7 0 surface % 82.4% 76.9% 3.8% 24.1% 0.0% Open Count 1 0 26 0 0 cupboard % 5.9% 0.0% 33.3% 0.0% 0.0% Familiar Count 0 5 0 1 0 bottle % 0.0% 19.2% 0.0% 3.4% 0.0% Mother or Count 1 0 34 0 0 father medications % 5.9% 0.0% 43.6% 0.0% 0.0%

Count 1 0 1 3 0 Buy it % 5.9% 0.0% 1.3% 10.3% 0.0%

Used or Count 0 1 0 3 1 present at % 0.0% 3.8% .0% 10.3% 50.0% work <0.001* Used at Count 0 0 12 15 0 home and the pt able to % 0.0% 0.0% 15.4% 51.7% 0.0% get it Pt’s Count 0 0 2 0 0 medication % 0.0% 0.0% 2.6% 0.0% 0.0% Inhabitant in Count 0 0 0 0 1 surrounding environment % 0.0% 0.0% 0.0% 0.0% 50.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

106

RESULTS

Relation between type of poison and vital signs: Table (40) shows significant relations (p 0.002) between them as in most cases of toxicity with drug of abuse vital signs were affected. Relation between amount of poison and vital signs: Table (41) shows

significant relations (p 0.002) between them as in most cases poisoned with above toxic dose vital signs were affected.

Table (40): Relation between type of poison and vital signs

Main types of poison Vital signs p-value Drug abuse Household Medication Pesticide Snake bite Count 7 22 49 23 2 Normal % 41.2% 84.6% 62.8% 79.3% 100.0%

Count 10 4 29 4 0 0.002* Affected

% 58.8% 15.4% 37.2% 13.8% 0.0% Count 0 0 0 2 0 Shocked % 0.0% 0.0% 0.0% 6.9% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Table (41): Relation between amount of poison and vital signs

Amount of poison Vital signs p-value Unknown Blew Just the Above the Not amount toxic dose toxic dose toxic dose toxic Count 36 8 15 23 21 Normal % 73.5% 88.9% 65.2% 46.0% 100.0% Count 13 1 8 25 0 Affected <0.001* % 26.5% 11.1% 34.8% 50.0% 0.0% Count 0 0 0 2 0 Shocked % 0.0% 0.0% 0.0% 4.0% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

107

RESULTS

Relation between type of poison and CNS manifestation: Table (42) shows significant relations (p<0.001) between them as in most cases of toxicity with drug of abuse and 50% of snake bite were drowsy.

Relation between amount of poison and CNS manifestation: Table (43) shows significant relations (p 0.001) between them.

Table (42): Relation between type of poison and CNS manifestation

Main types of poison CNS p- Drug Snake manifestations Household Medication Pesticide value abuse bite Count 0 23 58 16 1 Alert % 0.0% 88.5% 74.4% 55.2% 50.0% Count 13 1 18 13 1 Drowsy % 76.5% 3.8% 23.1% 44.8% 50.0% Count 1 1 1 0 0 Sleepy <0.001 % 5.9% 3.8% 1.3% 0.0% 0.0% Count 1 1 0 0 0 Deep coma % 5.9% 3.8% 0.0% 0.0% 0.0% Count 2 0 1 0 0 Convulsion % 11.8% 0.0% 1.3% 0.0% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

108

RESULTS

Table (43): Relation between amount of poison and CNS manifestation

Amount of poison CNS Blew Just the Above p- Unknown Not manifestations toxic toxic the toxic value amount toxic dose dose dose Count 27 9 14 27 21 Alert % 55.1% 100.0% 60.9% 54.0% 100% Count 17 0 8 21 0 Drowsy % 34.7% 0.0% 34.8% 42.0% 0.0% Count 3 0 0 0 0 Sleepy 0.001* % 6.1% 0.0% 0.0% 0.0% 0.0% Count 1 0 0 1 0 Deep coma % 2.0% 0.0% 0.0% 2.0% 0.0% Count 1 0 1 1 0 Convulsion % 2.0% 0.0% 4.3% 2.0% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between type of poison and specific antidote: Table (44) shows significant relation (p<0.001) between them as in most cases of pesticide and 50% of snake bite took the full regimen of specific antidote.

109

RESULTS

Table (44): Relation between type of poison and specific antidote

Main types of poison Specific antidote p-value Drug Snake Household Medication Pesticide abuse bite The drug Count 14 18 48 4 0 has no specific antidote % 82.4% 69.2% 61.5% 13.8% 0.0% supportive TTT only Not given Count 1 0 4 0 1 and supportive % 5.9% 0.0% 5.1% 0.0% 50.0% TTT only <0.001* Given in full Count 1 0 3 21 1 regimen % 5.9% 0.0% 3.8% 72.4% 50.0% Given and Count 1 0 0 3 0 improved before full % 5.9% 0.0% 0.0% 10.3% 0.0% regimen The pt not Count 0 8 23 1 0 admitted and no need % 0.0% 30.8% 29.5% 3.4% 0.0% to antidote

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between type of poison and admission: Table (45) shows significant relation (p<0.001) between them as most cases of different poisons admitted.

110

RESULTS

Table (45): Relation between type of poison and admission

Main types of poison Admission p-value Drug Snake Household Medication Pesticide abuse bite Count 17 18 53 29 2 Admitted % 100.0% 69.2% 67.9% 100.0% 100% <0.001* Not Count 0 8 25 0 0 admitted % 0.0% 30.8% 32.1% 0.0% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between amount of poison and admission: Table (46) shows significant relation (p<0.001) between them.

Table (46): Relation between amount of poison and admission

Amount of poison Admission Blew Just the Above p-value Unknown Not toxic toxic the toxic amount toxic dose dose dose Count 42 4 23 50 0 Admitted % 85.7% 44.4% 100.0% 100.0% 0.0% <0.001* Not Count 7 5 0 0 21 admitted % 14.3% 55.6% 0.0% 0.0% 100.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between type of poison and outcome: Table (47) shows significant relations (p<0.001) between them as most cases of drug of abuse, household products, medications, pesticide and 50% of snake bite improved and discharged.

111

RESULTS

Table (47): Relation between type of poison and outcome

Main types of poison Outcome Drug p-value Snake of Household Medication Pesticide bite abuse Count 0 0 0 1 0 Died % 0.0% 0.0% 0.0% 3.4% 0.0% Improved Count 10 9 36 24 1 and discharged % 58.8% 34.6% 46.2% 82.8% 50.0% Count 0 5 0 0 0 Complicated % 0.0% 19.2% 0.0% 0.0% 0.0% <0.001* Discharge on Count 7 4 17 4 1 his parent responsibility % 41.2% 15.4% 21.8% 13.8% 50.0% The drug Count 0 8 25 0 0 already not affect the pt so no specific % 0.0% 30.8% 32.1% 0.0% 0.0% outcome

Chi square (χ2) test *p-value <0.05 is statistically significant

112

RESULTS

Relation between type of poison and period of admission: Table (48) shows significant relations (p 0.005) between them.

Table (48): Relation between type of poison and period of admission

Main types of poison Period of admission p- (in Hrs) Drug of value Household Medication Pesticide Snake bite abuse Mean 41.41 30.69 28.96 45.38 34.00 ±S.D 19.75 26.90 27.27 18.27 14.14 Median 36.00 30.00 24.00 48.00 34.00 0.005* Minimum 20.00 0.00 0.00 2.00 24.00 Maximum 96.00 72.00 96.00 72.00 44.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Fig. (28): Correlation coefficient between type of poison and period of admission

Fig. (28): shows positive correlation coefficient (positive R value) between type of poison and period of admission as when severity of type of poison increase the period of admission increase and vice versa.

113

RESULTS

Relation between amount of poison and period of admission: Table (49) shows significant relations (p<0.001) between them.

Table (49): Relation between amount of poison and period of admission

Period of Amount of poison p- admission value in Hrs. Unknown blew toxic Just the toxic Above the Not amount dose dose toxic dose toxic Mean 36.90 7.33 33.30 50.10 0.00 ±S.D 21.59 10.49 15.07 22.94 0.00 Median 36.00 0.00 30.00 48.00 0.00 <0.001 Minimum 0.00 0.00 12.00 2.00 0.00 Maximum 72.00 28.00 72.00 96.00 0.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Fig. (29): Correlation coefficient between amount of poison and period of admission

Fig. (29): shows positive correlation coefficient (positive R value) between type of poison and period of admission as when the dose of poison increase the period of admission increase and vice versa.

114

RESULTS

(C) Hours of Delay: Relation between delay in Hrs and decontamination treatment: Table (50) shows a significant relation (p 0.035).

Table (50): Relation between hrs of delay and decontamination treatment

Delay in hrs. Decontamination p-value Mean ±S.D Median Minimum Maximum Not done 3.53 2.25 3.00 1.00 12.00 Gastric lavage and charcoal 2.43 0.74 2.00 1.00 4.00 0.035* Charcoal only 2.81 1.38 3.00 1.00 8.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

The relation between hours of delay and period of admission: Table (51) shows positive correlation coefficient when the hrs. of delay increase the period of admission increase and vice versa.

Table (51): Correlation coefficient between hrs of delay and period of admission

Period of admission Correlation Coefficient 0.225 Delay in hrs. p-value 0.005 N 152

Spearman correlation *p-value <0.05 is statistically significant

115

RESULTS

no t done 35% do ne in good way do ne in wrong way 62% 3%

Fig. (30): Pie chart shows percentage distribution of cases according to 1st aid

Distribution of cases according to 1st aid: Fig. (30) shows that about in 62% of cases 1st aid was not done, while in 35% of case 1st aid was done in wrong way and finally in 3% of cases 1st aid was done in good way. Relation between 1st aid and outcome: Table (52) show no significant relation (p 0.758) between them.

Table (52): Relation between 1st aid and outcome

1st aid

Done in good Done in wrong p- Outcome Not done way way value

Count % Count % Count %

Died 0 0.0% 0 0.0% 1 1.9% Improved and discharged 50 52.6% 2 50.0% 28 52.8% Complicated 3 3.2% 0 0.0% 2 3.8% 0.758 Discharged on his parent 22 23.2% 0 0.0% 11 20.8% responsibility The drug already not affect the pt so 20 21.1% 2 50.0% 11 20.8% no specific outcome

Chi square (χ2) test p-value ≥0.05 is statistically insignificant

116

RESULTS

(E) Vital signs and CNS manifestation:

normal affected shocked 1% 31%

68%

Fig. (31): Pie chart percentage distribution of cases according to vital signs

Regarding to vital signs: Fig. (31) shows that 68% of cases were with normal vital signs.

alert 64.50% drowsy sleepy

30.30% deep coma convulsion 2.00% 2.00% 1.30%

Fig. (32): Bar chart shows percentage of CNS manifestation of cases

Regarding to CNS manifestation, Fig. (32) shows that most cases were alert (64.5%) followed by drowsy (30.3%). Relation between vital signs and outcome: Table (53) shows significant relation (p<0.001) between them.

117

RESULTS

Table (53): Relation between vital signs and outcome

Vital signs p- Outcome Normal Affected Shocked value Count % Count % Count % Died 0 0.0% 0 0.0% 1 50.0% Improved and discharge 49 47.6% 30 63.8% 1 50.0% Complicated 2 1.9% 3 6.4% 0 0.0% <0.001 Discharge on his parent 19 18.4% 14 29.8% 0 0.0% responsibility The drug already not affect the pt 33 32.0% 0 0.0% 0 0.0% so no specific outcome

Chi square (χ2) test *p-value <0.05 is statistically significant

Relation between CNS manifestation and outcome: Table (54) shows significant relations (p<0.001) between them.

Table (54): Relation between CNS manifestation and outcome

CNS manifestations

Outcome Alert Drowsy Sleepy Deep coma Convulsion p-value Count % Count % Count % Count % Count %

Died 0 0.0% 1 2.2% 0 0.0% 0 0.0% 0 0.0% Improved and 44 44.9% 31 67.4% 3 100.0% 1 50.0% 1 33.3% discharged

Complicated 4 4.1% 0 0.0% 0 0.0% 1 50.0% 0 0.0% <0.001* Discharged on his 17 17.3% 14 30.4% 0 0.0% 0 0.0% 2 66.7% parent responsibility The drug already not 33 33.7% 0 0.0% 0 0.0% 0 0.0% 0 0.0% affect the pt

Chi square (χ2) test *p-value <0.05 is statistically significant

118

RESULTS

Relation between vital signs and period of admission: Table (55) shows a significant relation (p<0.001) between them. Relation between CNS manifestation and period of admission: Table (56) shows significant relation (p 0.006) between them.

Table (55): Relation between vital signs and period of admission

Vital signs Period of admission in Hrs. p-value Normal Affected Shocked Mean 28.43 46.40 18.00 ±S.D 24.89 22.69 16.97 Median 28.00 48.00 18.00 <0.001 Minimum .00 2.00 6.00 Maximum 96.00 96.00 30.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Table (56): Relation between CNS manifestation and period of admission

CNS manifestation Period of admission p- Alert Drowsy Sleepy Deep coma Convulsion value Mean 29.11 40.43 42.00 72.00 54.00 ±S.D 27.71 16.55 6.00 0.00 36.50 Median 24.00 36.00 42.00 72.00 36.00 0.006 Minimum 0.00 2.00 36.00 72.00 30.00 Maximum 96.00 72.00 48.00 72.00 96.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

119

RESULTS

(I) DATA OF POISON SEVERITY SCORING (PSS) AND APACHEII SCORING:

Regarding the relation between main type of poison and PSS: Table (57) shows significant relations (p<0.001) between them as majority of cases of household products, while majority of cases of medications were of moderate severity.

Table (57): Relation between main type of poison and PSS

Main types of poison Poison severity p-value according to PSS Drug of Snake Household Medication Pesticide abuse bite Count 0 6 14 0 0 No severity % 0.0% 23.1% 17.9% 0.0% 0.0% Count 0 11 21 15 1 Low severity % 0.0% 42.3% 26.9% 51.7% 50.0% <0.001* Moderate Count 16 5 43 12 1 severity % 94.1% 19.2% 55.1% 41.4% 50.0% Count 1 4 0 2 0 High severity % 5.9% 15.4% 0.0% 6.9% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Regarding the relation between main type of poison and APACHE II: Table (58) shows significant relations (p<0.001) between them.

120

RESULTS

Table (58): Relation between main type of poison and APACHE II

Main types of poison Mortality according p-value to APACHE II (%) Snake Drug of abuse Household Medication Pesticide bite

Mean 19.29 13.27 8.83 14.93 11.50

±S.D 5.79 14.43 5.72 13.21 4.95

Median 15.00 8.00 8.00 8.00 11.50 <0.001*

Minimum 8.00 0.00 0.00 8.00 8.00

Maximum 25.00 55.00 15.00 75.00 15.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Fig. (33): Correlation between main type of poison and APACHE II

Figure (33) shows positive correlation between main type of poison and APACHE II significant relation with medications and household product in group 1, while significant relation with drug of abuse and pesticide in group 2. Regarding the relation between amount of poison and PSS: Table (59) shows significant relations (p<0.001) between them.

121

RESULTS

Table (59): Relation between amount of poison and PSS

Amount of poison Blew Just the Above Severity according to PSS Unknown p-value toxic toxic the toxic Not toxic amount dose dose dose Count 5 0 0 0 15 No severity % 10.2% 0.0% 0.0% 0.0% 71.4% Count 14 7 8 13 6 Low severity % 28.6% 77.8% 34.8% 26.0% 28.6% <0.001* Count 27 2 15 33 0 Moderate severity % 55.1% 22.2% 65.2% 66.0% 0.0% Count 3 0 0 4 0 High severity % 6.1% 0.0% 0.0% 8.0% 0.0%

Chi square (χ2) test *p-value <0.05 is statistically significant

Regarding the relation between amount of poison and APACHE II: Table (60) shows significant relations (p<0.001) between them. Positive correlation between amount of poison and APACHE II was found as shown in Fig. (34).

Table (60): Relation between amount of poison and APACHE II

Mortality Amount of poison according to p-value Unknown Blew toxic Just the toxic Above the APACHE II (%) Not toxic amount dose dose toxic dose

Mean 13.49 9.44 13.96 14.54 1.14

±S.D 10.30 4.48 6.43 10.94 1.85

Median 8.00 8.00 15.00 15.00 0.00 <0.001*

Minimum 4.00 4.00 4.00 4.00 0.00

Maximum 55.00 15.00 25.00 75.00 4.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

122

RESULTS

Fig. (34): Correlation between amount of poison and APACHE II

Regarding to relation between history of previous disease and APACHE II: Table (61) shows significant relation (p<0.012) between them. Positive correlation between history of previous disease and APACHE II as shown in Fig. (35).

Table (61): Relation between history of previous disease and APACHE II

History of previous disease Mortality according to APACHE II (%) Yes and Yes and not No p-value associated associated

Mean 11.51 18.75 13.25 ±S.D 10.25 5.18 3.50 Median 8.00 15.00 15.00 0.012 Minimum 0.00 15.00 8.00 Maximum 75.00 25.00 15.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

123

RESULTS

Fig. (35): Correlation between history of previous disease and APACHE II

Regarding to relation between vital signs and PSS: Table (62) shows significant relation (p<0.001) between them.

Table (62): Relation between vital signs and PSS

Vital signs Severity according to PSS Normal Affected Shocked p-value Count % Count % Count % No severity 20 19.4% 0 0.0% 0 0.0% Low severity 47 45.6% 1 2.1% 0 0.0% <0.001 Moderate severity 34 33.0% 43 91.5% 0 0.0% High severity 2 1.9% 3 6.4% 2 100%

Chi square (χ2) test *p-value <0.05 is statistically significant

Regarding the relation between vital signs and APACHE II: Table (63) shows significant relation (p<0.001) between them. There was also a positive correlation between them (Fig. 36).

124

RESULTS

Table (63): Relation between vital signs and APACHE II

Mortality according to Vital signs p- APACHE II (%) value Normal Affected Shocked Mean 9.22 16.34 50.00 ±S.D 8.12 7.52 35.36 Median 8.00 15.00 50.00 <0.001 Minimum .00 8.00 25.00 Maximum 55.00 40.00 75.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Fig. (36): Correlation between vital signs and APACHE II

Regarding the relation between CNS manifestation and PSS: Table (64) shows significant relation (p<0.001) between them as majority of alert cases showed low severity and all cases of deeply comatose cases showed high severity. Regarding the relation between CNS manifestation and APACHE II: Table (65) shows significant relation (p<0.001) between them.

125

RESULTS

Table (64): Relation between CNS manifestation and PSS

Severity CNS manifestation according Alert Drowsy Sleepy Deep coma Convulsion p- to PSS value Count % Count % Count % Count % Count % No 20 20.4% 0 0.0% 0 0.0% 0 0.0% 0 0.0% severity Low 47 48.0% 1 2.2% 0 0.0% 0 0.0% 0 0.0% severity <0.001 Moderate 28 28.6% 43 93.5% 3 100.% 0 0.0% 3 100.% severity High 3 3.1% 2 4.3% 0 0.0% 2 100% 0 0.0% severity

Chi square (χ2) test *p-value <0.05 is statistically significant

Table (65): Relation between CNS manifestation and APACHE II

Mortality according to CNS manifestation APACHE II (%) Alert Drowsy Sleepy Deep coma Convulsion p-value Mean 8.83 16.37 18.33 40.00 21.67 ±S.D 7.78 10.38 5.77 21.21 5.77 Median 8.00 15.00 15.00 40.00 25.00 <0.001 Minimum .00 8.00 15.00 25.00 15.00 Maximum 40.00 75.00 25.00 55.00 25.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

126

RESULTS

Fig. (37): Correlation between CNS manifestation and APACHE II

Figure (37) shows positive correlation between them. The relation between period of admission and APACHE II: Table (66) shows positive correlation between them with positive R value as when mortality rate increases the period of admission increases and vice versa.

Table (66): Correlation between period of admission and APACHE II

Mortality according to APACHE II (%) Correlation Coefficient 0.551 Period of admission p-value < 0.001 N 152

Spearman correlation *p-value <0.05 is statistically significant

Regarding the relation between period of admission and PSS: Table (67) shows significant relation (p<0.001) between them.

127

RESULTS

Table (67): Relation between period of admission and PSS

Severity according to PSS Period of Low High p- admission No severity Moderate severity severity severity value Mean 0.00 30.50 43.36 48.86 ±S.D 0.00 26.66 19.48 25.32 <0.001 Median 0.00 28.00 40.00 48.00 Minimum 0.00 0.00 2.00 6.00 Maximum 0.00 96.00 96.00 72.00

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant

Fig. (38): Correlation between period of admission and PSS

Positive correlation between period of admission and PSS was found (Fig. 38).

The relation between outcome and APACHE II: Table (68) shows significant relation (p<0.001) between them.

128

RESULTS

Table (68): Relation between outcome and APACHE II

Mortality according to APACHE II (%) Outcome (fate) p- Mean ±S.D Median Minimum Maximum value Died 75.00 . 75.00 75.00 75.00 Improved and discharged 12.60 5.72 15.00 4.00 25.00 Complicated 40.00 10.61 40.00 25.00 55.00 <0.001 Discharge on his Parent 13.45 5.47 15.00 8.00 25.00 responsibility The drug already no toxic effect 2.76 3.27 4.00 .00 15.00 on the PT

Non-parametric Kruskal-Wallis test *p-value <0.05 is statistically significant.

Fig. (39): Correlation between outcome and APACHE II

129

RESULTS

Regarding correlation between outcome and APACHE II, Fig. (39) shows positive correlation between them. Relation between outcome and PSS: Table (69) shows significant relation (p<0.001) between them as majority of cases which showed low severity and moderate severity improved and discharged.

Table (69): Relation between outcome and PSS

severity according to PSS Moderate High Outcome No severity Low severity severity severity p-value Count % Count % Count % Count % Died 0 0.0% 0 0.0% 0 0.0% 1 14.3% Improved and 0 0.0% 27 56.2% 51 66.2% 2 28.6% discharged

Complicated 0 0.0% 0 0.0% 1 1.3% 4 57.1% <0.001* Discharge on his 0 0.0% 8 16.7% 25 32.5% 0 0.0% parent responsibility The drug already no 20 100% 13 27.1% 0 0.0% 0 0.0% toxic effect on the pt

Chi square (χ2) test *p-value <0.05 is statistically significant

130

DISCUSSION

Childhood poisoning is a major cause of morbidity in the developing as well as the developed countries. In spite of the success of some interventions to prevent accidental poisoning in the pediatric population, toxic ingestion continues to occur commonly. Globally, the pattern of childhood poisoning is changing rapidly (Akhtar et al., 2006).

Poisoning might occur accidental or intentional whether suicidal or homicidal. Accidental poisoning is common among preschool age children because they are very active to explore the world around them e.g. the surfaces of tables, kitchen counters and bath room. Their curiosity goes anywhere and everything goes into the mouth (Soori, 2001). Poisoning in childhood is a complex interaction between the child, hazardous substance and environmental factors (Singh, 2007).

In older children and adolescents, suicide attempts are more common (Mutlu et al., 2010). It may be a manifestation of insecurity, self-injury due to guilty feelings or attention seeking behavior (Trangadia et al., 2016).

Child homicide is a rare, yet is a tragic, event that occurs at rate of 2.0 per 100,000 inhabitants globally (Cavanagh et al., 2005). It most commonly occurs in infants within the first two years in their life. Homicidal toxicity may be due to psychological disturbance of caregivers (Bonsignore et al., 2016).

The epidemiology of poisoning statistically studied from many perspectives. These include overall mortality, hospital admission rates, and enquiries to Poisons Information Services (Bateman, 2007).

131

DISCUSSION

While, the American Association of Poison Control Centers reports approximately 1.6 million potentially toxic exposures for children and adolescents ages 0 to 19 years during the year 2007, and these pediatric exposures represent 64.7% of the reported exposures for all age groups during this year (Bronstein et al., 2008).

The total cases of acute poisoning among children admitted at Ain Shams University in Cairo (poison control center) during the year 2008 were 8841 (Ain-Shams Poison Control Center, 2008).

The present study was conducted on one hundred and fifty two of Egyptian participant of both sex in age blew 18 years old ; 96 females and 56 males. They were classified into 4 age groups; toddlers (1-<3 yrs), early childhood (3-<9 years), late childhood (9-<13 years) and adolescent (13-<18 years).

While according to manner of toxicity, they classified into 2 groups; accidental (unintentional) toxicity group (1) and suicidal toxicity (group 2). The number of accidental toxicity cases was 89 cases (58.6%), while the number of suicidal toxicity cases was 63 cases (41.4%). Also, in our present study, the drug poisoning was the commonest cause of poisoning in NECTR followed by pesticide poisoning.

While the total cases of acute poisoning among children admitted at Tanta University Hospital and El-Menshawy General Hospital during the year 1998 was 434 cases. Where, food poisoning was the commonest cause of poisoning followed by drug poisoning (Maklad & El-Saleet, 1999), the leading cause of acute poisoning among children in Alexandria Poison Center during the year 1992 was household agents followed by food poisoning then drug poisoning respectively (Abd El-Megid & Salem, 1995).

132

DISCUSSION

CONCERNING SOCIO-DEMOGRAPHIC STUDY

The cause and type of poisoning vary in different parts of the world and within the country also depending upon factors such as education, demography, socioeconomic factors, customs and local belief (Devaranavadagi et al., 2017).

Age distribution in the present study, toddlers (1-<3yrs) represented the majority of cases (44%) followed by (adolescents (13-<18 yrs), (early childhood (3-<9 yrs) and (late childhood (9-<13 yrs) who represented (35%), (14%) and (7%) respectively.

This result almost agrees with the study conducted by Hassan & Siam. (2014) who collected their data from Zagazig University Hospitals-Egypt, during the period from January 2011 to August 2012, where children aged from 1 to 3 yrs represented most of the cases (70%). It is also approved with Agarwal et al. (2016) and Barakizou et al. (2016). This can be explained as toddlers have over curiosity and explore their world by their mouth so it more affected with toxicity (Singh, 2007).

While this result disagreed with Devaranavadagi et al. (2017), who collected their data from Paediatric Intensive Care, Kempegowda Institute of Medical Sciences and Research Centre, Karnataka-India, from August 2015 to July 2016, where children aged above 10 yrs. represented most of cases (60.5%).

Regarding age and manner of toxicity in the present study, toddlers (1-<3yrs) represented the majority of accidental cases group 1 (75.3%) followed by early childhood, while adolescent (13-<18 yrs) represented the majority of suicidal cases group 2 (84.1%) and this showed a significant relation (p<0.001).

133

DISCUSSION

This result approved with Aggarwal et al. (2014) who collected their data from a tertiary care teaching hospital at Dehradun, in Uttarakhand. The most cases of accidental toxicity occurred in children aged blew 12 yrs (97%), while most of suicidal toxicity occurred in adolescent (13-18 yrs) (80.4%) and it is also approved by Dnyanesh et al. (2014) and Gupta et al. (2003). This may be explained as toddlers have over curiosity and explore their world by their mouth (Singh, 2007), while adolescent lives stressful life and have many physiological and emotional disturbance during this age (Trangadia et al., 2016).

Regarding to relation between age and type and amount of poisons in the present study, medications were represented the common poisons in early childhood (68.2%), adolescent (58.5%) and late childhood (80%) respectively, while in toddlers the medications and household products represented the common poisons and this showed significant relations (p0.004).

This result approved with a study conducted by Devaranavadagi et al., (2017) who collected their data from Paediatric Intensive Care, Kempegowda Institute of Medical Sciences and Research Centre, Karnataka-India, from August 2015 to July 2016, as Household products and medications represented majority of toxicity in children aged blew 5 yrs, while in children aged above 10 yrs medications represented majority of toxicity and this is also approved with Barakizou et al., (2016) and Dehghani et al., (2015).

Our speculation: this may be explained as medications and household products are the most available poisons indoors and the children can easily get and use it.

While this result disapproved with study conducted by Trangadia et al., (2016) who collected their cases from the Department of Forensic Medicine, Shri M.P. Shah Govt. Medical College, GGG hospital Jamnagar-

134

DISCUSSION

India, during the period of 1 year, as the main type of poison there was kerosene followed by other household products, and snake bites . This may be explained as Indians are using kerosene as main source of foul in homes and snakes are common there (Jesslin et al., 2010).

In the present study, most cases of toddlers (56.7%) and early childhood (27.3%) in group 1 took unknown amount of poison, while most cases of adolescent (60%) and late childhood (67.9%) in group 2 took above the toxic dose and this is showed significant relations (p 0.023) in group 1 and not reach to significance in group 2. Unfortunately, no paper studied this point.

Our speculation: in accidental cases the children unable to tell us the proper amount of poisons that they took, while in suicidal cases they took large dose available during their attempts.

Regarding to relation between age and availability of poison and the most probable cause of toxicity, in group 1 most of toddlers reached the poison in low surface and the most probable cause of toxicity among them was negligence, while most childhood reached it on open board and the most probable cause of toxicity among them was over curiosity . In group 2 most of adolescent and late childhood took their parents’ medications and the most probable cause of toxicity among them was family problems and this is showed significant relations (p <0.001) in group 1 and not reach to significance in group 2. Unfortunately, no paper studied this point.

Our speculation: leaving poisonous material in low surface and open board is considered negligence especially with the presence of children in toddlers in early childhood age group due to their over activity and exploration of surrounding, while loss of proper connection with late childhood and adolescent and family leads to many problems leading to their attempts by using the most available poison in home which is their parents’ medications.

135

DISCUSSION

Regarding sex distribution in the present study, females represented the majority of studied cases (63.2%) in comparison to males who represented (36.8%).

This result approved with study conducted by Azab et al., (2016) who collected their cases from Ain Shams University's Poisoning Treatment Center, Egypt, as females represented 55.9% of cases while males represented 44.1% of cases and this is also approved with Barakizou et al., (2016) and Sahin et al., (2011).

Our speculation, this may be explained as in group 1, young females receive less attention from their caregivers and in suicidal toxicity group 2, females are more liable to emotional and physiological changes.

This result disapproved with study conducted by Hassan & Siam. (2014) who collected their data from Zagazig University Hospitals during the period from January 2011 to August 2012, Egypt as males represented 56.3% of cases, while female represented 43.7% of cases and this also reported by Trangadia et al., (2016). Male children are known to be more active and restless as compared to their female counterparts and that nature could be the responsible factor of higher poisoning incidence (Trangadia et al., 2016).

Regarding sex and manner of toxicity in the present study, most of the cases in accidental toxicity group 1 were males (53.9%), while most of cases in suicidal toxicity group 2 were females (87.3%) and this is showed significant relations (p<0.001).

This result approved with study conducted by Azab et al., (2016) who collected their cases from Ain Shams University's Poisoning Treatment Center, Egypt, as, most of the cases in accidental toxicity were males (85.8%), while most of cases in suicidal toxicity were females (44.7%) and this is also approved with Hegazy et al., (2012). Male children are known to

136

DISCUSSION

be more active and restless, while female adolescents have higher tendency of internalizing emotional and behavioral problems (Kaess et al., 2011).

Regarding to relation between sex and (type of poison and its amount), most of females took medications and household products above the toxic dose, while most of males took medications in unknown amount and this is showed significant relations (p 0.004) (p 0.015). Unfortunately, no paper studied this point.

Our speculation: suicidal toxicity was common among females so they took poisons during their attempts with the largest available amount of the poison, while accidental toxicity (group1) was common in male toddlers & early childhood, so took the common available poison in unknown amount.

Regarding to the relation between sex and the most probable cause of toxicity, as the most common cause of toxicity in males was negligence, while the most probable cause of toxicity in females was family problems. While psychological disturbance, school problem, emotional disturbance and wrong medication were almost the other caused of toxicity in female children comparing to male children in significant relations (p<0.001). Unfortunately, no paper studied the probable causes of toxicity.

Our speculation: In the present study, suicidal toxicity (group 2) was common among females due to family problems, where females are more liable to emotional and physiological changes (as mentioned before). Also, females generally receive less attention. While accidental toxicity was common in males, due to negligence in addition to their over activity & curiosity.

Regarding residence distribution in the present study, cases came from rural area represented (52%), while cases came from urban area represented (48%).

137

DISCUSSION

This result approved with study conducted by Hassan & Siam, (2014) who collected their data from Zagazig University Hospitals-Egypt during the period from January 2011 to August 2012, as most cases came from rural area (68%), while minority of cases came from urban area (32%) and this is also approved with Dehghani et al., (2015) and Agarwal et al., (2016).

On our speculum, this may be due to improper storage of chemicals and household poisonous substances and also, lower level of care towards children in rural areas.

On other hand, our result disapproved with study conducted by Trangadia et al., (2016) who collected their cases from the Department of Forensic Medicine, Shri M.P. Shah Govt. Medical College, GGG hospital Jamnagar, India, during the period of 1 year, as cases came from rural area represented (24.02%), while cases came from urban area represented (75.98%).

Our speculation, the lack of care and awareness from rural people to go to hospitals.

Regarding residence and manner of toxicity in the present study, most of accidental cases came from rural area, while most of suicidal cases came from urban area and showed significant relation (p0.004).

This result approved with study conducted by Agarwal et al., (2016) who collected their cases from department of pediatrics at S. P. M. college and associated group of hospital Bikaner, Rajasthan, India. Most of accidental cases came from rural area, while most of suicidal cases came from urban area.

138

DISCUSSION

Our speculation, it may be explained as lack of education and attention of parent in rural area. In addition, in urban area life is much more stressful as mentioned be before.

On other hand, our result disapproved with study conducted by Aggarwal et al., (2014) who collected their data from a tertiary care teaching hospital at Dehradun, in Uttarakhand. As most of accidental and suicidal cases came from urban area.

On our speculum, this may because India has different life style and culture.

Regarding the relation between residence and type of poison, most of rural cases took pesticide, while most of urban cases took medications. Also, the snake bite was reported only in rural cases. This is showed significant relations (p<0.001), but unfortunately, no paper studied this point.

Our speculation based on WHO report about children and poisoning see (Appendix 2). The prevalence and types of poisoning vary in different parts of the world and also in different parts of the countries. They depend on industrial development, agricultural activities, cultural practices relating to supervision of children and local beliefs and customs. For example, medicinal drugs are the leading cause of non-fatal poisoning in children in middle income to high-income countries, and ingestion of fuels such as kerosene is a common cause in low-income countries.

Regarding residence and 1st aid, and Relation between residence and hours of delay, most of 1st aid was done in wrong way in rural case, while 1st aid not done in urban area and this is showed a significant relation (p<0.001). Also, there was significant relation between residence and hours of delay. Unfortunately, no paper studied this point.

139

DISCUSSION

Our speculation: It is due to lack of awareness and education in rural area in contrast to urban area. In addition to the distant between the residence and the NECTR, where the majority of cases occurred at home (89.5%).

Regarding the relation between residence and (availability of poison & the most probable cause of toxicity), the most of rural cases got poison from low surface, while most of urban cases got poison as it was their parents medication and this is showed significant relations (p<0.001). On other hand, regarding the most cause of toxicity among rural cases, it was negligence while among urban cases was family problems followed with negligence and this is showed significant relations (p 0.004). Unfortunately, we could not find any paper about these points.

Our speculation: It is due to lack of awareness and education in rural area in contrast to urban area. While stressful life in urban area leads to improper communication between parent and their children.

Regarding to educational level of cases in the present study, majority of cases was preschool (nursery age) represented (52.6%) followed by secondary school, preparatory, primary and not educated representing (21.7%), (15.8%), (7.9%) and (2%) respectively. While, regarding the relation between manner of toxicity and educational level of the patients, most of accidental cases (group1) was preschool age, while most of suicidal cases (group 2) was in secondary school followed with preparatory.

These results were consistent with study conducted by Trangadia et al. (2016) who collected their cases from the Department of Forensic Medicine, Shri M.P. Shah Govt. Medical College, GGG hospital Jamnagar-India, during the period of 1 year, as most cases was preschool age represented (70.58%) of cases and these were also approved with Chhetri et al. (2013).

140

DISCUSSION

This may explained as most of cases were accidental toxicity and it is common among toddlers (nursery age) (Kholi & Kuttiat, 2008). While the adolescent (in secondary school) lives stressful life and have many physiological and emotional disturbance during this age (Trangadia et al., 2016).

Regarding to relation between educational level and type & amount of poison, medications were common poison among preschool, while pesticide was common poison among non-educated cases and this is showed significant relations (p<0.001).

Most of preschool and non-educated cases took unknown amount of toxin and this is showed significant relations (p<0.001). Unfortunately, no paper studied these points.

Our speculation is that the lack of awareness in preschool and non- educated cases make them unable to tell us the proper dose they took from the most available poison.

Regarding to relation between educational level and the most probable cause of toxicity, the most probable cause in preschool cases was negligence, while in secondary school was family problems and this is showed significant relations (p<0.001). Unfortunately, no paper studied this points.

Our speculation: as the children in preschool age need more attention as they are over active and curious to explore the surrounding, while during secondary school they undergo many of physiological and emotional changes need more support from their families.

141

DISCUSSION

Regarding to educational level of participants' fathers in the present study, majority of their fathers were not educated and low education represented 50.6% followed by moderate education 27%.

This result approved with study conducted by Chhetri et al. (2013) who collected their cases from PICU and or children ward of Patan Hospital, as most cases fathers were illiterate or had attended only primary schools 41% followed by 20% secondary education and 14% higher education and it is also approved with Alazab et al. (2012).

On our speculum, this may explained as non-educated fathers and of low education unable to give their children proper care and interest.

Regarding to educational level of participants' mothers in the present study, majority of mothers were not educated and low education represented 51.6% followed by high education and moderate education represented 27.9% and 20.4%.

This result approved with study conducted by Alazab et al. (2012) who collected their cases from the Poisoning Unit of a university hospital in Egypt, as most cases mothers were illiterate or had up to primary education 41.9% followed by 31.4% secondary and 18.5% higher education and this is also approved with Chhetri et al. (2013).

Our speculation is that, non-educated mothers and of low education don’t have considerable knowledge's about chemicals and their risks on children. In addition, they unable to give their children proper care and interest.

Concerning the employment status of participants' mothers parents in the present study, fathers were working in 94.7% of cases, while mothers were working in 30.2%.

142

DISCUSSION

This result is consistent with the study conducted by Alazab et al. (2012) who collected their cases from the Poisoning Unit of a university hospital in Egypt, as fathers were working in 96.1% of cases, while mothers were working in 46%. Our speculation, as in most cases the father responsible for the financial support of the family.

Regarding the relation between parents’ work & education and the manner of toxicity (in both studied groups), there were significant relations. Where most of accidental cases, their fathers were working and not educated, while most of suicidal cases, their fathers were working and moderate education. On other hand, shows that most of accidental cases the mother was housewife and not educated, while most of suicidal cases, mothers were (housewife and not educated) and (working and moderate educated) both of them represented. Unfortunately, no paper studied these points.

Our speculation is, in general, children's toxicity increases among low and moderate social-economic level, due to lack of education and attention to their children.

Regarding to relation between mother work & education and the availability of poison, there were significant relations (p<0.001). The cases of mother (working and high educated) and (working and moderate educated) took their parents’ medications, while most housewife and not educated mother’s cases took toxins at low surface. Again, no paper studied this point.

Our speculation: The improper packaging of medications is due to lack of knowledge of non-educated mothers about the risk of available substances at home. In addition, the lack of attention to children as a working mother (even if educated) may has not sufficient time for proper care-giving.

143

DISCUSSION

Concerning the relation between parents’ work & education and most probable cause of toxicity, most cases of working and not educated or low education negligence was the most probable cause of toxicity and this is showed significant relations (p 0.001). On other hand, most cases of housewife and not educated or educated and working even with high education the neglect was the most probable cause of toxicity and this is showed significant relations (p 0.002). Unfortunately, no paper studied these points.

Our speculation, due to parents’ lack of education and awareness leading to increase incidence of toxicity and easy availability of poisonous materials, while in educated working mothers, they are stressful not fully oriented with their children. Also, there is increased incidence of toxicity where the life is finically stressful with no enough time for proper care-giving that any child needs.

Our speculation, as when the socioeconomic level of the family improved their awareness increase about the importance of early presentation of the patient to hospital. In addition to the distance factor between the residence and the NECTR.

144

DISCUSSION

CONCERNING TOXICITY DATA STUDY

According to manner of toxicity in the present study, majority of cases were accidental toxicity (58.6%). while suicidal cases and homicidal cases represented (41.4%) and (0%) respectively. Regarding to availability of poison, that most available poisons were on low surface (28.9%).

This result was consistent with the study conducted by Barakizou et al. (2016) who collected their cases from the Department of Pediatrics, the Military Hospital, Tunis, as majority of case were accidental (74%), while suicidal cases (26%) and homicidal were (0%) and this is also approved with Trangadia et al. (2016) and Aggarwal et al. (2014). Children become mobile, they learn to open cabinets and to examine the content, children begin to walk, and they may be able to grab items that were previously out of reach. Improved fine motor skills enable toddlers to open simple screw on caps or bottle tops. Normal curiosity and desire for oral stimulation may cause children to place new objects directly into mouth for tasting or swallowing (Osaghee & Sule, 2013).

This result disapproved with study conducted by Dehghani et al. (2015) who collected their cases from the emergency department of Shahid Beheshti hospital of Kashan (center of Iran), as most cases were suicidal (50.59%), while accidental cases represented (38.09%). This may be explained as the suicide rate is higher than other type of poisoning in Iran. The reduction in the standard level of socio-economic life may be a reason for this increasing rate through the country (Dehghani et al., 2015).

According to type of poison, most cases poisoned with medication (52%) followed by pesticide (19%), household product (17%), drug of abuse (11%) and snake bite (1%).

145

DISCUSSION

This result approved with study conducted by Barakizou et al. (2016) who collected their cases from the Department of Pediatrics, the Military Hospital, Tunis, as the most common type of poisons was drugs (medications) (82%) and this is also approved with Ahmad, (2014) and Hegazy et al., (2012).

Our speculation, is that parents leave their medicines in open board or low surface that is easily reached by children, in addition to improper packaging of medications.

This result disapproved with study conducted by Dnyanesh et al. (2014) who collected their cases from the PICU records of all the pediatric patients (a tertiary care center in Karnataka), India, as The agents most frequently used were hydrocarbons (43.1%), pyrethrine compounds 15.5%, Organo-Chlorine compounds 12.1% drugs, Organo-Phospherous compounds 12.1%, drugs 1.8%. Our speculation, this may be explained as these agents are most commonly used and available in India.

According to manner of toxicity in both studied groups and common type of poison, in group 1 (accidental cases) (43.8%), while in group 2 (suicidal cases) was (61.9%) took medications. Unfortunately, no paper studied this points.

Our speculation, medications the most available poison in different home regardless their socio-economic level.

According to location of exposure, majority of cases exposed to poison at home (89.5%), while the remaining cases exposed to poison outside home (10.5%).

146

DISCUSSION

This result approved with study conducted by Azab et al. (2016) who collected their cases from Ain Shams University's Poisoning Treatment Center, Egypt, as most cases exposed to poison at home (97.8%), while 2.2% exposed to poison outside home and this is also approved by Hassan & Siam, (2014) and Alazab et al. (2012). This may be explained as homes are the main familiar place to children (Trangadia et al., 2016).

Regarding to the relation between type of poison and its availability, drug of abuse & household products were at low surface, while parents’ medications and most of pesticide were available at home and patients able to reach it and this is showed significant relations (p <0.001). Unfortunately, we couldn’t find paper about that point.

Our speculation, as toxicity with drug of abuse and household product was common among low and moderate socio-economic level so they don’t care where they put the poison, while in most cases they put the medication in relatively high surface but the child use something to reach it or she/he is old enough to get it easily.

Regarding to type and amount of poison and vital signs, most cases of toxicity with drug of abuse vital signs were affected and this is showed significant relations (p 0.002).

On other hand, most cases poisoned with above toxic dose vital signs were affected and this is showed significant relations (p 0.002). Unfortunately, no paper studied this points.

As clinical presentation of occult ingestion varies depending upon the ingested substance and can range from asymptomatic to critically ill. Occult toxic exposure should be considered in the differential diagnosis of children who present with acute onset of multiorgan system dysfunction, altered

147

DISCUSSION

mental status, respiratory or cardiac compromise, unexplained metabolic acidosis, seizures, or a puzzling clinical picture (Velez et al., 2012).

Regarding to the relation between type & amount of poison and CNS manifestation, showed significant relations (p<0.001). where most cases of toxicity with drug of abuse and 50% 0f snake bite were drowsy.

On other hand, most cases took unknown amount and just toxic dose were alert, while most cases took above toxic dose were drowsy. Unfortunately, we couldn’t find any paper studied these points.

The neurological manifestations are developed due to many factors direct toxic effect of poison on the central nervous system, hypoxia secondary to pulmonary involvement and so many effects which cause involvement of CNS (Lifshitz et al., 2003).

Regarding to type and amount of poison and period of admission, showed significant relations (p 0.005) (p<0.001) between them. Positive correlation coefficient between type and amount of poison and period of admission was found, as when severity of type and dose of poison increased the period of admission increased and vice versa.

This result is consistent with study conducted by Chibwana et al. (2001) who collected their cases from pediatric ward of the Queen Elizabeth central hospital, Blantyre, Malawi, as they found significant relation between type and amount of poison and hospital stay.

Our speculation, as the severity of the clinical picture is depending on the type and amount of poisoning (Velez et al., 2012) and period of admission is depending on severity of clinical picture which consequently changes in different poisons and amount.

148

DISCUSSION

Regarding to type of poison and outcome, most cases of drug of abuse, household products, medications, pesticide and 50% of snake bite improved and discharged and this is showed significant relations (p<0.001). Unfortunately, we couldn’t find any paper studied that point.

Our speculation: in the present study, children toxicities were easily diagnosed and properly treated, so most cases improved and discharged.

According to hospitalization (admission) in the present study, majority of cases admitted (78.3%), while the non-admitted cases represented (21.7%).

This result approved with study conducted by Dehghani et al. (2015) who collected their cases from the records of all poisoned patients admitted to the emergency department of Shahid Beheshti hospital of Kashan (center of Iran), as majority of cases admitted (55.54%), while the non-admitted cases represented (43.45%) and this is also approved by Barakizou et al., (2016).

As some poisons have a delayed effect and you’re a child may have to stay in hospital, possibly overnight (Joshi, & Ross, (2017).

Regarding to the relation between hours of delay and decontamination treatment, it is showed a significant relation (p 0.035). Unfortunately, we couldn’t find paper studied that point.

As the decontamination treatment is typically initiated immediately. In most cases, the time elapsed prior to specific centers renders further decontamination efforts relatively useless after admission (Even et al., 2014).

149

DISCUSSION

Regarding to vital signs: 68% of cases were with normal vital signs, while 31% of cases were with affected vital signs and finally 1% was shocked.

This result approved with study conducted by Alazab et al. (2012) who collected their cases from the Poisoning Unit of a university hospital in Egypt, as most cases were with normal vital signs and minority of cases were with affected vital signs.

A wide range of medicines are accidentally ingested by children. Many are of very low toxicity (Riordan et al., 2002).

On another aspect, the prognosis of acute poisoning depends on the exposure of toxin, the amount of toxin ingestion and the physiology of compensation (Yu et al., 2012).

Regarding to CNS manifestations, most cases were alert (64.5%) followed by drowsy (30.3%), sleepy (2%), convulsion (2%) and deep coma (1.3%).

This result was almost approved with a study conducted by Alazab et al. (2012) who collected their cases from the Poisoning Unit of a university hospital in Egypt, as 98.8% of cases were free, while 0.7% and 0.5% of cases presented with convulsion and hallucination respectively and this is also approved by Sowmya et al. (2014).

The CNS effects of drugs and chemicals can be divided into drugs that cause altered mental status, seizures, encephalopathy and movement disorders (Rivera et al., 2003).

150

DISCUSSION

Regarding to the relation between vital signs or CNS manifestations and outcome, there were significant relations (p<0.001). Where, most cases of normal, affected and 50% of shocked cases improved.

On other hand, most cases with different CNS manifestations also improved and discharged Also, regarding to the relation between vital signs or CNS manifestations and period of admission, there were significant relations between them. Where cases with affected vital signs and deep comatose cases were admitted for the longest period. Unfortunately, no papers studied these points.

Vital signs role in assessing severity of poisoned patients is still lack of evidence (Yu et al., 2012).

Not only the type, but also the number of abnormal vital signs, were predictive for adverse outcome (Barfod et al., 2012).

Regarding to 1st aid, it was not done in 62% of cases, while in 35% of case 1st aid was done but in wrong way.

This result is consistent with study conducted by Chibwana et al. (2001) who collected their cases from pediatric ward of the Queen Elizabeth central hospital, Blantyre, Malawi, about 81.9% 1st aid not done outside the hospital while 16% done in right way and 2.1% done but in wrong way.

Regarding to Treatment of cases, most cases took charcoal only (50.7%), while 27% of cases underwent to gastric lavage and took charcoal and finally 22.4% of cases did not undergo to decontamination treatment. Cases with available specific antidote were 19.7% of cases, while cases with no specific antidote were 55.3%.

151

DISCUSSION

This result approved with study conducted by Srinivasa et al. (2016) who collected their cases from the Department of Pediatrics of a tertiary care teaching hospital, Karnataka, India, as 70% took symptomatic treatment with no specific antidote, while 25% of cases took specific antidote.

As Different treatments are available, the choice of line of treatment is depending on the poison (Mowry et al., 2015).

This result disapproved with study conducted by Hegazy et al. (2012) who collected their cases from the routinely registered data during attendance of poisoned cases in the different Makkah Hospitals, KSA, as 59.8% took specific antidote, while 23.1% had no specific antidote. GIT decontamination was done in 46.4% of cases, while activated charcoal was given in 45.6%.

Our speculation, the Treatment changes according to the type of poisons and available facilities in each study.

Regarding to final outcome, most of cases (52.6%) improved and discharged, while 21.7% discharged on his parent responsibility, 3.3% complicated and 0.7% died.

In spite of our results showed the highest percentage of cases improved and discharged, while the least percentage died being in consistent with those of many studies, but concerning the percentage values that were disagreed with them. Where, in a study conducted by Hegazy et al. (2012) who collected their cases from the routinely registered data during attendance of poisoned cases in the different Makah Hospitals-KSA, as 74.6% of cases improved and discharged, while 0.6% of cases died and this is also approved with by Hassan & Siam, (2014). As the child toxicity is easily preventable and early and proper management allow complete recovery (Hyder et al., 2008).

152

DISCUSSION

CONCERNING POISON SEVERITY SCORING (PSS) AND ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION (APACHE) II SCORING DATA

Regarding to the relation between main type or amount of poison and PSS, showed significant relations (p <0.001) between them. Where majority of cases of household products (42.3%), pesticide (51.7%) and 50% of snake bite were of low severity, while majority of cases of medications (55.1%) and the other 50% of snake bite were of moderate severity. On the other hand, the PSS increased once the dose of poison increased, as most cases with low dose showed low severity while most cases with dose above toxic dose showed moderate and high severity.

This result approved with study conducted by Azab et al. (2016) who collected their cases from Ain Shams University's Poisoning Treatment Center - Egypt, as majority of cases of household products (90.4%) and pesticide (54.9%) were of low severity, while most cases of medication were of low and moderate severity.

The influence of intra- and interrater variation, and predominance of minor cases on the study findings should be taken into account when interpreting this data (McFarland et al., 2017).

Regarding to the relation between main types or amount of poison and APACHE II, there were significant relations (p<0.001) between them. Where APACHE II (%) was high in cases of drug abuse toxicity. Also, positive correlations between them were found. Where APACHE II (%) was the least in cases taking below toxic amount of poison and increased with the increasing of poison amount. Unfortunately, we couldn’t find any paper about these points.

153

DISCUSSION

There were significant correlations between APACHE II score and the following variables: plasma concentration, estimated ingested amount in different poisons for example paraquat (Huang et al., 2003).

Regarding to history of previous disease and APACHE II, there is significant relation (p <0.012) between them and positive correlation. Unfortunately, we couldn’t find paper about this point.

Our speculation, as APACHE II scoring scores for acute physiology and chronic health diseases so once the patient has previous history of disease this will increase the APACHE II scoring (Appendix 3).

Regarding to the relation between (vital signs and CNS manifestations) and PSS, as majority of alert cases showed low severity and all cases of deeply comatose cases showed high severity and this is showed significant relations (p<0.001). On the other hand, the patients with normal vital signs showed low severity, affected showed moderate severity and shocked showed high severity and this is showed significant relations (p<0.001). Unfortunately, we couldn’t find any paper about these points.

The severity of poisoning differs depending upon the nature of the compound and its quantity, the way through which the exposure has occurred and the time at which treatment is initiated as in organo-phosphorous (Kim et al., 2013).

Our speculation, as PSS scoring increases once the clinical manifestation severity increases from this clinical manifestation vital signs and CNS manifestations.

Regarding to (vital signs and CNS manifestations) and APACHE II, there were significant relations (p<0.012) between them and positive correlations. Unfortunately, we couldn’t find paper about these points.

154

DISCUSSION

Our speculation, as APACHE II scoring scores for acute physiology and chronic health diseases so once the acute physiology becomes more affected the APACHE II scoring will increase and vice versa.

Regarding to period of admission and (APACHE II and PSS), there were significant relations (p <0.001) between them and positive correlations. Unfortunately, we couldn’t find any paper about these points.

Our speculation, when the clinical manifestations become more sever the period of admission will increase.

Regarding to outcome and APACHE II, there were significant relations (p<0.001) between them and positive correlations. Unfortunately, we couldn’t find paper about this point.

As long as poisoning patients are treated appropriately, their mortality reduced.

The SOFA score is more useful than the APACHE II for predicting the outcomes of ICU poisoned patients, as the method for calculating SOFA scores is easier and simpler than that for APACHE II as in organophosphorous (OP) (Kim et al., 2013).

Regarding to outcome and PSS, majority of cases which showed low severity and moderate severity were improved and discharged, while most cases with high severity were complicated. This is showed significant relations (p<0.001). Unfortunately, we couldn’t find paper about this point.

Different approaches to the symptoms and signs in poisoning may better our understanding of the underlying mechanism that in turn may assist with the management of acutely poisoned patients as in OP (Peter et al., 2014).

155

CONCLUSION & RECOMMENDATIONS

CONCLUSION

From the present study, it was concluded that:

Toddlers were more commonly affected followed by (adolescents), (early childhood) and (late childhood). Accidental toxicity was more common than the suicidal toxicity in pediatric age group. Suicidal toxicity was common at adolescence & late childhood, while accidental toxicity was common at toddler & early childhood. Medications was the most common type of poison in age in accidental and suicidal toxicity. Toddlers & early childhood got the poison from low surface and open board, while adolescence & late childhood took their parents’ medications. Negligence and over curiosity were the most common cause of toxicity among toddler & early childhood, while family problems were the most common cause of toxicity among adolescence & late childhood. Home was the common location of toxicity in different age groups. Females were more affected than males. The majority of cases came from rural area. Suicidal toxicity was common at females and in urban cases, while accidental toxicity was common at males and rural cases. Medications and household were more common in females, while medications were more common in males. Pesticide was more common in rural area, while medications were more common in urban area. Negligence was the most common cause of toxicity among males and rural cases, while family problems were the most common cause of toxicity among females and urban cases. Most of 1st aid was done in wrong way in rural case and not done in urban area.

156

CONCLUSION & RECOMMENDATIONS

Most of rural cases got poison from low surface, while most of urban cases got poison as it was their parents’ medications. There is a significant relation between residence and hours of delay. The majority of cases in present study was preschool (nursery age) followed by secondary school, preparatory, primary and not educated . Suicidal toxicity was common among secondary school students and in law and moderate socio-economic level, while accidental toxicity was common among preschool age and in low socio-economic level. Medications were common poison among preschool, while pesticide was common poison among non-educated cases. Negligence was the most common cause of toxicity among preschool age, while family problems were the most common cause of toxicity among secondary school student. Most cases of high and moderate socio-economic level took their parents’ medications, while most cases of low socio-economic level got poison from law surface. There is a significant relation between socio-economic level and hours of delay. Most of available poisons were on low surface followed by parents’ medications. Medications were the most common poison in both accidental and suicidal toxicity followed by pesticide. Most cases ingested above the toxic dose of poison followed by unknown amount. Drug of abuse & household products were at low surface, while parents’ medications and most of pesticide were available at home and patients able to reach it Vital signs and CNS manifestations were commonly affected in drug of abuse and in high dose of poison. There is significant relations and positive correlations between type and amount of poison.

157

CONCLUSION & RECOMMENDATIONS

Positive correlation coefficient between hours of delay and period of admission. Most cases were alert and with normal vital signs. Most cases with different vital signs and CNS manifestations improved and discharged on other hand there is significant relations between period of admission and vital signs and CNS manifestation. majority of cases of household products, while majority of cases of medications were of moderate severity according to PSS. There is a significant relation and positive correlation between APACHE II and type and amount of poison, history of previous disease, vital signs, CNS manifestations, period of admission and outcome. According to PSS most cases of normal vital signs showed no severity, while most cases of affected showed moderate severity and most cases of shocked showed high severity. According to PSS majority of alert cases showed low severity and all cases of deeply comatose cases showed high severity. According to PSS most cases of low severity and moderate severity improved and discharged. There is positive relation and correlation between PSS and period of admission. Most of cases improved and discharged, while only 3.3% of cases complicated.

158

CONCLUSION & RECOMMENDATIONS

RECOMMENDATIONS

Simple safety measures are the best way to make sure your child cannot get access to poisons. When buying medications, household chemicals and garden products, choose childproof containers if possible. Ask for pills and tablets in blister packs and foil strips. Put all poisons out of reach of children after using or buying them and use child resistant locks on cupboards containing poisons. Always read the labels of all medications and follow the instructions when giving medication to your child. Do not confuse children by talking about pills and liquid medication as ‘lollies’ and store poisons and medications in their original containers. If you take pills, do so out of sight of children. Discard old medications, batteries and poisons. Your local council can advise you where to dispose of them. Parents and caregivers should consider doing a first aid course. Attention to the psychology of children, especially girls and give them more care. avoid the problems and do not involve children in it because they lead to psychological disorders and attempts to commit suicide. Take care of the working woman in the work and allow them to give proper care to her children for more attention to them. Raise the level of education And the culture of the parents Increase awareness of the parents about rapid presentation of their children to specialized center to treat cases of poisoning or even suspected poisoning. Aware of the parents to complete treatment and not rush to take their children to their responsibility before the completion of treatment. Post the poison control center number near the telephone. Training courses to junior doctors about how to deal with emergency cases of pediatric poisoning.

159

CONCLUSION & RECOMMENDATIONS

Increase awareness of doctor about the risk of poisoning on affected vital signs and CNS manifestations and this leads to increase severity of poisoning and its’ outcome. In school should give more care and support to children in different stages to avoid further stress on them. After attempt of suicide in pediatric age group we should refer the patient to specialized psychiatrist.

160

SUMMARY

Each year, huge number of patients under 6 years come to the emergency department with history of poisoning. Almost always accidental poisoning in children occurs under 5 year of age. In older children and adolescents, suicide attempts are more common. Poisoning may result from pica, thirst or hunger. It may be a manifestation of insecurity, self-injury due to guilty feelings or attention seeking behavior.

The present work was a descriptive, cross-sectional study, including one hundred and fifty two of Egyptian participant of both sexes (96 females and 56 males).

They were classified into 4 age groups; toddlers (1-<3 yrs) (44%), early childhood (3-<9 yrs) (14%), late childhood (9-<13 yrs) (7%) and adolescent (13-<18 yrs) (35%).

While according to manner of toxicity, they classified into 2 groups; accidental (unintentional) toxicity group (1) and suicidal toxicity (group 2). The number of accidental toxicity cases was 89 cases (58.6%), while the number of suicidal toxicity cases was 63 cases (41.4%). Relation between age and manner of toxicity in the present study was significant, as toddlers (1-<3yrs) represented the majority of accidental cases group 1 (75.3%) followed by early childhood, while adolescent (13-<18 yrs) represented the majority of suicidal cases group 2 (84.1%) .

161

SUMMARY

Relation between age and type and amount of poisons in the present study was significant, as medications were represented the common poisons in early childhood (68.2%), adolescent (58.5%) and late childhood (80%) respectively, while in toddlers the medications and household products represented the common poisons. Relations between age and availability of poison and the most probable cause of toxicity were significant, in group 1 most of toddlers reached the poison in low surface and the most probable cause of toxicity among them was negligence, while most childhood reached it on open board and the most probable cause of toxicity among them was over curiosity . In group 2 most of adolescent and late childhood took their parents’ medications and the most probable cause of toxicity among them was family problems. Sex distribution in the present study, females represented the majority of studied cases (63.2%) in comparison to males who represented (36.8%). Comparison between sex and manner of toxicity in the present study was significant, most of the cases in accidental toxicity group 1 were males (53.9%), while most of cases in suicidal toxicity group 2 were females (87.3%). Relation between sex and (type of poison and its amount) was significant, most of females took medications and household products above the toxic dose, while most of males took medications in unknown amount. Relation between sex and the most probable cause of toxicity, as the most common cause of toxicity in males was negligence, while the most probable cause of toxicity in females was family problems. While psychological disturbance, school problem, emotional disturbance and wrong medication were almost the other caused of toxicity in female children comparing to male children in significant relations.

162

SUMMARY

Residence distribution in the present study, cases came from rural area represented (52%), while cases came from urban area represented (48%). Residence and manner of toxicity in the present study, most of accidental cases came from rural area, while most of suicidal cases came from urban area and showed significant relation. Relation between residence and type of poison was significant, most of rural cases took pesticide, while most of urban cases took medications. Also, the snake bite was reported only in rural cases. Residence and 1st aid, and Relation between residence and hours of delay were significant, most of 1st aid was done in wrong way in rural case, while 1st aid not done in urban area. Relation between residence and (availability of poison & the most probable cause of toxicity) was significant, the most of rural cases got poison from low surface, while most of urban cases got poison as it was their parents medication. On other hand, regarding the most cause of toxicity among rural cases, it was negligence while among urban cases was family problems followed with negligence. Educational level of cases in the present study, majority of cases was preschool (nursery age) represented (52.6%) followed by secondary school, preparatory, primary and not educated representing (21.7%), (15.8%), (7.9%) and (2%) respectively. While, the relation between manner of toxicity and educational level of the patients, most of accidental cases (group1) was preschool age, while most of suicidal cases (group2) was in secondary school followed with preparatory. Relation between educational level and type & amount of poison was significant, medications were common poison among preschool, while pesticide was common poison among non-educated cases. Most of preschool and non-educated cases took unknown amount of toxin. Comparison between educational level and the most probable cause of toxicity was significant, the most probable cause in preschool cases was negligence, while in secondary school was family problems

163

SUMMARY

Educational level of participants' fathers in the present study, majority of their fathers were not educated and low education represented 50.6% followed by moderate education 27%. Educational level of participants' mothers in the present study, majority of mothers were not educated and low education represented 51.6% followed by high education and moderate education represented 27.9% and 20.4%. Concerning the employment status of participants' mothers parents in the present study, fathers were working in 94.7% of cases, while mothers were working in 30.2%. Relation between parents’ work & education and the manner of toxicity (in both studied groups), there were significant relations. Where most of accidental cases, their fathers were working and not educated, while most of suicidal cases, their fathers were working and moderate education. On other hand, shows that most of accidental cases the mother was housewife and not educated, while most of suicidal cases, mothers were (housewife and not educated) and (working and moderate educated) both of them represented. Relation between mother work & education and the availability of poison were significant. The cases of mother (working and high educated) and (working and moderate educated) took their parents’ medications, while most housewife and not educated mother’s cases took toxins at low surface. Concerning the relation between parents’ work & education and most probable cause of toxicity was significant, most cases of working and not educated or low education negligence was the most probable cause of toxicity. On other hand, most cases of housewife and not educated or educated and working even with high education the neglect was the most probable cause of toxicity.

164

SUMMARY

Relation between parents' work and education and (hours of delay), there is a significant relation between them and positive correlation between father work & education and hours of delay, also between mother work & education and hours of delay. Regarding to availability of poison, that most available poisons were on low surface (28.9%). According to type of poison, most cases poisoned with medication (52%) followed by pesticide (19%), household product (17%), drug of abuse (11%) and snake bite (1%). According to manner of toxicity in both studied groups and common type of poison, in group 1 (accidental cases) (43.8%), while in group 2 (suicidal cases) was (61.9%) took medications. According to location of exposure, majority of cases exposed to poison at home (89.5%), while the remaining cases exposed to poison outside home (10.5%). Relation between type of poison and its availability was significant, drug of abuse & household products were at low surface, while parents’ medications and most of pesticide were available at home and patients able to reach it. Comparison between type and amount of poison and vital signs was significant, most cases of toxicity with drug of abuse vital signs were affected. Relation between type & amount of poison and CNS manifestation was significant. where most cases of toxicity with drug of abuse and 50% 0f snake bite were drowsy. Regarding to type and amount of poison and period of admission, showed significant relations and Positive correlation coefficient between type and amount of poison and period of admission was found. Relation between type of poison and outcome was significant, most cases of drug of abuse, household products, medications, pesticide and 50% of snake bite improved and discharged.

165

SUMMARY

According to hospitalization (admission) in the present study, majority of cases admitted (78.3%), while the non-admitted cases represented (21.7%). Relation between hours of delay and decontamination treatment, it is showed a significant relation. Regarding to vital signs, 68% of cases were with normal vital signs, while 31% of cases were with affected vital signs and finally 1% was shocked. Regarding to CNS manifestations, most cases were alert (64.5%) followed by drowsy (30.3%), sleepy (2%), convulsion (2%) and deep coma (1.3%). Relations between vital signs or CNS manifestations and outcome was significant, where, most cases of normal, affected and 50% of shocked cases improved.

On other hand, most cases with different CNS manifestations also improved and discharged Also, Relation between vital signs or CNS manifestations and period of admission, there were significant relations between them. Where cases with affected vital signs and deep comatose cases were admitted for the longest period. Regarding to 1st aid, it was not done in 62% of cases, while in 35% of case 1st aid was done but in wrong way. Regarding to Treatment of cases, most cases took charcoal only (50.7%), while 27% of cases underwent to gastric lavage and took charcoal and finally 22.4% of cases did not undergo to decontamination treatment. Cases with available specific antidote were 19.7% of cases, while cases with no specific antidote were 55.3%. Regarding to final outcome, most of cases (52.6%) improved and discharged, while 21.7% discharged on his parent responsibility, 3.3% complicated and 0.7% died. Relations between main type or amount of poison and PSS were significant, Where majority of cases of household products (42.3%),

166

SUMMARY

pesticide (51.7%) and 50% of snake bite were of low severity, while majority of cases of medications (55.1%) and the other 50% of snake bite were of moderate severity. On the other hand, the PSS increased once the dose of poison increased, as most cases with low dose showed low severity while most cases with dose above toxic dose showed moderate and high severity. Regarding to the relation between main types or amount of poison and APACHE II, there were significant relations (p<0.001) between them. Where APACHE II (%) was high in cases of drug abuse toxicity. Also, positive correlations between them were found. Where APACHE II (%) was the least in cases taking below toxic amount of poison and increased with the increasing of poison amount. Regarding to history of previous disease. (vital signs and CNS manifestations), period of admission and out come and APACHE II, there were significant relations between them and positive correlations. Relations between (vital signs and CNS manifestations) and PSS were significant, as majority of alert cases showed low severity and all cases of deeply comatose cases showed high severity. On the other hand, the patients with normal vital signs showed low severity, affected showed moderate severity and shocked showed high severity. Regarding to outcome and PSS was significant, majority of cases which showed low severity and moderate severity were improved and discharged, while most cases with high severity were complicated.

167

REFERENCES

REFERENCES (A) Abd El-Megid L.A.N., & Salem E.M. (1995): Children poisoning, prevention strategies. Mansoura Journal of Forensic Medicine and Toxicology; 3 (2): 71-85. Abdolkarim, P.; Shahin, S.; Ali, R., et al (2004): Benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides, J. Physiol. Paris, 23 (12): 565-569. Afshari, R. & Ghooshkhanehee, H. (2009): Tramadol overdose induced seizure, dramatic rise of CPK and acute renal failure. J. Pak. Med. Assoc. 59: 178. Afshari, R.; Afshar, R. & Mégarbane, B. (2011): Tramadol overdose: review of the literature. Ré-animation. 20 (5): 436-441. Agarwal, G., Bithu, K.S., & Agarwal, R. (2016): An epidemiological study of acute poisoning in children in a tertiary care hospital of western Rajasthan, India. International Journal of Contemporary Pediatrics, 3 (4): 1249-1251. Aggarwal, B., Rana, S.K., & Chhavi, N. (2014): Pattern of Poisoning in Children, an Experience From a Teaching Hospital in Northern India, JK SCIENCE .16 (4): 174-178 Ahmad, B. (2014): Accidental childhood poisoning. Journal of Rawalpindi Medical College, 18 (2): 216-218. Ain-Shams Poison Control Center (2008): Total number of cases of pediatric poisoning (<18 year) admitted to Ain -Shams Poison Control Center during the year 2008 and examples of the most common pediatric poisoning admitted during this year. Akerele, E. & Olupona, T. (2017): Drugs of Abuse. Psychiatric Clinics, 40 (3): 501-17. Akhtar, S., Rani, G.R., & Al-Anizi, F. (2006): Risk factors in acute poisoning in children-A retrospective study. Kuwait Medical Journal, 38 (1), 33-36. Alazab RM, Elmougy MT, Fayad RA, et al. (2012): Risk factors of acute poisoning among children: A study at a poisoning unit of a University hospital in Egypt. South East Asia Journal of Public Health; 2 (2): 41-7.

168

REFERENCES

Alazab RM. (2012): Determinants of Acute Poisoning among Children (1-60) months old data Poisoning Unit of a University Hospital, Egypt, are Employed Mothers a Risk Factor? Retrospective Cohort Study. Journal of American Science.; 8 (9): 1107-17 Alcorn J & McNamara PJ . (2002): Ontogeny of hepatic and renal systemic clearance pathways in infants: part I. Clin Pharmacokinet 41: 959–998 Alcorn J & McNamara PJ. (2003): Pharmacokinetics in the newborn. Adv Drug Deliv Rev 55: 667–686 Algin, A., & Erdogan, M. O. (2017): The investigation of blood drug levels and course of acetaminophen poisoning due to application time. Biomedical Research, 28 (15): 6682-6686. Alije Keka, Ramosaj A, Toro H, et al (2014): Acute poisoning in children; changes over the years, data of pediatric clinic department of toxicology. P 56-8. Al-Naddawi, M., Al-Chalabi, M. A. Q., & Kamil, K. M. (2009): Kerosene Poisoning In Children. Iraq postgraduate medical journal, 8 (4); 350-356. American Academy of Pediatrics (2001): Acetaminophen Toxicity in Children. Pediatrics. 108: 4. Available at http: //pediatrics.aappublications. org/content/108/4/1020 Anderson BJ. (2012): Pharmacology in the very young: anaesthetic implications. Eur J Anaesthesiol; 29: 261–270. Anderson GD. (2010): Developmental pharmacokinetics. Semin Pediatr Neurol 17: 208–213 Anderson, G. D., & Lynn, A. M. (2009): Optimizing pediatric dosing: a developmental pharmacologic approach. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 29 (6); 680-690. Andiran N & Sarikayalar F. (2004): Pattern of acute poisonings in childhood in Ankara: what has changed in twenty years? The Turkish Journal of pediatrics. 46: 147-52 Anzenbacher P & Zanger UM. (2012): Metabolism of drugs and other xenobiotics. 1st ed. Weinheim, Germany: Wiley-VCH. Ardakani, Y.H. & Rouini, M-R. (2007): Pharmacokinetics of Tramadol and its Three Main Metabolites in Healthy Male and Female Volunteers. Biopharm. Drug Dispos. 28: 526–533.

169

REFERENCES

Armstrong SC., & Cozza KL. (2003): Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: Theory and clinical reality, Part II. Psychosomatics. 44: 515–520 Arunachalam, R., & Rammohan, A. (2016): Corrosive Injury of the Upper Gastrointestinal Tract: A Review. Arch Clin Gastroenterol.2 (1): 056-062. Ashok, A. H., Mizuno, Y., Volkow, N. D., et al (2017): Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta- analysis. JAMA psychiatry.74 (5): 511-519 Azab, S. M., Hirshon, J. M., Hayes, et al (2016): Epidemiology of acute poisoning in children presenting to the poisoning treatment center at Ain Shams University in Cairo, Egypt, 2009–2013. Clinical Toxicology, 54 (1), 20-26.

(B) Baber NS. (2005): Paediatric regulatory guidelines: do they help in optimizing dose selection for children? Br J Clin Pharmacol. 59 (6): 660–2 Balali, M. M. & Balali, M. K. (2005): Nerve agents. In: Brent J, (ed.): Critical Care Toxicology. 2nd ed., 1st Vol., Elsevier Mosby, Philadelphia, USA, Chap-3, 1379 – 1393. Balbakay, G (2014): The Legislations of the Rights of Children between Islamic and Ordinances Laws. Jil of Human Rights Journal. (5): 30-47. Bamouni YA, Bonkoungou P & Nacro B. (1999): Aspects radiologiques del’intoxication aigue au pe´trole en milieu hospitalier pe´diatrique. Med Afrique Noire.46: 78–82 Barakizou, H., Rjeb, Y. B., Gannouni, S., et al (2016): Acute Drug Poisoning in Tunisian Children & 58; About 150 Cases. Iranian Journal of Toxicology, 10 (3): 1-5. Barfod, C., Lauritzen, M. M. P., Danker, J. K., et al. (2012): Abnormal vital signs are strong predictors for intensive care unit admission and in-hospital mortality in adults triaged in the emergency department-a prospective cohort study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 20 (1), 28.

170

REFERENCES

Barile, F.A. (2004): Opioids and derivatives In Clinical toxicology. Principles and Mechanisms. Barile, F.A. (eds.) Taylor & Francis e- Library, Washington D.C. PP: 121-132. Bartelink, I.H.; Rademaker, C.M.; Schobben, A.F., et al (2006): Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin. Pharma-cokinet. 45, 1077-1097. Baselt, R.C. & Cravey, R.H. (2011): Disposition of toxic drugs and chemicals in man. Seal Beach: Biomedical publications. 8: 1712-1715. Basu M. (2016): Socio-demographic factors, symptoms, complications and treatment of kerosene oil poisoning in children: A hospital based cross-sectional study Sri Lanka Journal of Child Health.45 (2): 72-75 Bateman DN (2007): The epidemiology of poisoning. Medicine. 35 (10): 537-539. Bates, M.N. & Blakely, T.A. (1999): Role of cannabis in motor vehicles crashes. Epidemiol Rev. 21 (2): 222-232. Benedetti MS & Baltes EL. (2003): Drug metabolism and disposition in children. Fund Clin Pharmacol.17: 281–299 Benedetti, M.S.; Whomsley, R. & Canning, M. (2007): Drug metabolism in the paediatric population and in the elderly. Drug Discov. 12: 599-610 Benois, A., Petitjeans, F., Raynaud, L., et al (2009): Clinical and therapeutic aspects of childhood kerosene poisoning in Djibouti. Tropical doctor. 39 (4): 236-238. Bindu A., Kumar, R. S & Nanda, C. (2014): Pattern of Poisoning in Children, an Experience From a Teaching Hospital in Northern India. JK Science Journal of Medical Education and Research. Oct-Dec; 16 (4): 174-178. Blanco JG, Harrison PL, Evans WE., et al. (2000): Human cytochrome P450 maximal activities in pediatric versus adult liver. Drug Metab Disp.28: 379–382. Bonsignore, A., Groppi, A., Ventura, F., et al. (2016): Fatal methadone intoxication in an infant listed as a homicide. International journal of legal medicine.130 (5): 1231-1235.

171

REFERENCES

Bourne, C.; Gouraud, A.; Daveluy, A. et al. (2013): Tramadol and hypo-glycaemia: comparison with other step 2 analgesic drugs. Br J Clin Pharmacol. 75 (4): 1063-1067. Bozkurt, P. (2005): Review article Use of tramadol in children. Pediatric Anesthesia. 15 (12): 1041–1047. Bradberry SM & Vale JA. (2003): Poisons initial assessment and management. Clin Med. 3: 107–10. Bronstein AC, Spyker DA, Cantilena LR Jr, et al (2010): 2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila) 48 (10) : 979 - 1178. Buck, M.L. (2002): Naloxone for the reversal of opioid adverse effects. Pediatric Pharmacotherapy. 8 (8): 1-4. Buckley, N.A.; Eddleston, M. & Szinicz, L. (2005): Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst. Rev., 2 (1): 50-85. Budhathoki S, Poudel P, Bhatta NK, et al. (2009): Clinical profile and outcome of poisoning and intoxication in children: A hospital based study. Nepal Med Coll J.11 (3): 170-5. Butchart, A. & Finney, A. (2006): Preventing Child Maltreatment: A Guide to Taking Action and Generating Evidence, Geneva: World Health Organization and ISPCAN p 10.

(C) Cashman JR & Zhang J. (2006): Human flavin-containing monooxygenases. Annu Rev Pharmacol Toxicol.46: 65–100 Cavanagh K, Dobash RE & Dobash RP. (2005): Men who murder children inside and outside the family. Br J Soc Work.35 (5): 667e88 Chan CK, Tse ML & Lau FL. (2012): Dettol poisoning and the need for airway intervention. Hong Kong Med J. 18 (4): 270–5. Chan YH (2003a): Biostatistics102: Quantitative Data – Parametric & Non-parametric Tests. Singapore Med J.44 (8): 391-396. Chan YH (2003b): Biostatistics 103: Qualitative Data–Tests of Independence. Singapore Med J.44 (10): 498-503.

172

REFERENCES

Chan YH (2003c): Biostatistics 104: Correlational Analysis. Singapore Med J.44 (12) : 614-619. Charehsaz M, Gürbay A, Karakılıç ME, et al (2011): Theophylline Adverse effects, poisoning and treatment approaches. J Clin Anal Med .2: 157-163.5 Cheraghali F & Taymori M. (2006): Epidemiological Study of Drug Intoxication in Children. Acta Medica Iranica. 44 (1): 37-40 Chhetri, U. D., Ansari, I., & Shrestha, S. (2013): Pattern of pediatric poisoning and accident in Patan Hospital. Kathmandu University medical journal, 10 (3): 39-43. Chibishev AA, Simonovska N, Bozinovska C, et al. (2014): Respiratory complications from acute corrosive poisonings in adults. Mater Sociomed. 26 (2): 80–3. Chibwana, C., Mhango, T., & Molyneux, E. M. (2001): Childhood poisoning at the Queen Elizabeth Central Hospital, Blantyre, Malawi. East African medical journal, 78 (6), 292-295. Chien, C., Marriott, J. L., Ashby, K., et al. (2003): Unintentional ingestion of over the counter medications in children less than 5 years old. Journal of paediatrics and child health.39 (4), 264-269. Chowdhury, F. R., & Ruhan, A. M. (2016): Household Poisoning. In Clinical Pathways in Emergency Medicine. Springer India. (pp. 503- 512). Clarke DJ, Moghrabi N, Monaghan G, et al. (1997): Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias. Clin Chim Acta 266: 63–74 Coen M. (2015): Metabolic phenotyping applied to pre-clinical and clinical studies of acetaminophen metabolism and hepatotoxicity. Drug Metab Rev.47: 29–4 Cohen-Wolkowiez, M., Moran, C., Benjamin, et al. (2009): Pediatric antifungal agents. Curr. Opin. Infect Dis. 22: 553-558. Contini S & Scarpignato C. (2013): Caustic injury of the upper gastrointestinal tract: a comprehensive review. World J Gastroenterol. 19 (25): 3918-30

173

REFERENCES

Contini S, Swarray-Deen A & Scarpignato C. (2009): Oesophageal corrosive injuries in children: a forgotten social and health challenge in developing countries. Bull World Org . 87 (12): 950-4.

(D) Daubin, C.; Quentin, C.; Goulle, et al. (2007): Refractory shock and asystole related to tramadol overdose. Clin Toxicol (Phila). 45 (8): 961-964. De Wildt SN, Kearns GL, Hop WC, et al. (2002): Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol. 53 (4): 390-392. De Wildt SN, Kearns GL, Leeder JS, et al. (1999): Cytochrome P450 3A: Ontogeny and drug disposition. Clin. Pharmacokinet. 37: 485–505. De Wildt SN, Kearns GL, Leeder JS, et al. (1999): Cytochrome P450 3A: Ontogeny and drug disposition. Clin Pharmacokinet.37: 485–505 De Wildt, S.N.; Johnson, T.N. & Choonara, I. (2003): The effect of age on drug metabolism. Paediatr. Perinatal Drug Ther. 101-106 Dehghani, R., Fathi, B., Aboo-Saaidi, Z., et al. (2015): Epidemiology of Poisonings in Shahid Beheshti Hospital in Kashan, Iran. International Journal of Medical Toxicology and Forensic Medicine, 5 (3): 144-150. Devaranavadagi, R. A., Patel, S., & Shankar, P. (2017): A study on profile of poisoning in pediatric population. International Journal of Contemporary Pediatrics, 4 (3): 810-815. Dinis-Oliveira, R. J., Carvalho, F., Duarte, et al. (2010): Collection of biological samples in forensic toxicology. Toxicology Mechanisms and Methods.20 (7): 363-414. Dnyanesh, D. K., Dnyanesh, S., & Bellad, R. (2014): Profile of paediatric poisoning at a tertiary care center in Karnataka. International Journal of Applied Sciences and Biotechnology. 2 (2): 142-145. Drummer O. H. (2007): Requirements for bioanalytical procedures in postmortem toxicology. Anal Bioanal Chem. 388: 1495–503.

174

REFERENCES

Drummer O.H. & Gerostamoulos D. (2002): Postmortem drug analysis: analytical and toxicological aspects. Ther Drug Monit. 24: 199–209 Drummer, O. H. (2004): Postmortem toxicology of drugs of abuse. Forensic Science International. 142 (2): 101-113. Dvir, H.; Silman, I.; Harel, M., et al. (2010): Acetylcholinesterase: from 3D structure to function. Chem. Biol. Interact., 187: 10

(E) Ecobichon, D.J. (2001): “Carbamate insecticides”, Handbook of Eddleston, M.; Buckley, N.A.; Eyer, P., et al. (2008a): Management of acute organophosphorus pesticide poisoning. Lancet, 371: 597–607. Eddleston, M.; Dawson, A.H. & Karalliedde, L. (2004b): Early management after self-poisoning with an organophosphorus or carbamate pesticide — a treatment protocol for junior doctors. Crit. Care.8: 391–397. Eddleston, M.; Haggalla, S.; Reginald, K., et al. (2007): The hazards of gastric lavage for intentional self-poisoning in a resource poor location. Clin. Toxicol.45: 136-143. Eddleston, M.; Juszczak, E.; Buckley, N.A., et al. (2008b): Multiple- dose activated charcoal in acute self-poisoning: a randomized controlled trial. Lancet.371: 579-586. Eddleston, M.; Karalliedde, L. & Buckley, N. (2002): Pesticide poisoning in the developing world—a minimum pesticide list. Lancet.360: 1163–1167. Ellis, E. F. (2007): Theophylline. In Allergic Diseases . Humana Press. pp. 343-359 El-Naggar, A. E. R., Abdalla, M. S., El-Sebaey, et al. (2009): Clinical findings and cholinesterase levels in children of organophosphates and carbamates poisoning. European journal of pediatrics.168 (8): 951. El-Okdi, N.S.; Lumbrezer, D.; Karanovic, D. et al. (2014): Serotonin Syndrome after the Use of Tramadol and Ziprasidone in a Patient with a Deep Brain Stimulator for Parkinson Disease. Am J Ther. 21 (4): e97-99.

175

REFERENCES

Elshabrawi, M., & A-kader, H. H. (2011): Caustic ingestion in children. Expert review of gastroenterology & hepatology.5 (5): 637- 645. Even KM, Armsby CC, Bateman ST (2014): Poisonings requiring admission to the pediatric intensive care unit: a 5-year review. Clin Toxicol (Phila).; 52 (5): 519–24.

(F) Farzaneh, E.; Mostfazadeh, B. and Mehrpour, O. (2012a): Seizurogenic effects of low-dose Naloxone in Tramadol overdose. Iranian Journal of Pharmacology & Therapeutics. 11 (1): 6-9. Fernandez, E., Perez, R., Hernandez, A., et al. (2011): Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics, 3 (1), 53-72. Fisher, J. (2015): Theophylline overdose.Reactions.1569: 205-19. Flaherty, E.G. & Macmillan H.L. (2013): Macmillan Committee on Child Abuse and Neglect, Caregiver-fabricated illness in a child: a manifestation of child maltreatment Pediatrics.132: 590-597 Flanagan RJ, Connally G & Evans JM. (2005): Analytical toxicology. Guidelines for sample collection post-mortem. Toxicol Rev. 24: 63–71. Flockhart DA. (2007): Drug interactions: Cytochrome P450 drug interaction table. Indiana University School of Medicine. [Online]. Available from: http://medicine.iupui.edu/clin-pharm/ddis/clinical- table/ [last accessed 1 May 2015]. Furue M, Terao H, Rikihisa W, et al. (2003): Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. Br J Dermatol. 148 (1): 128-133.

(G) Gair, R. & Kent, D. (2010): Tramadol: toxicity and treatment. Toxic Update Newsletter. 6: 1-4. Garrett, P.M. (2004): Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesth. Intensive Care. 32: 575–577.

176

REFERENCES

George C. Rodgers Jr. & Matyuns N J. (2004): Poisonings: Drugs, Chemicals, and Plants. In: Behrman RE, Robert M. Kliegman, Hal B. Jenson. Nelson Textbook of Pediatrics, 17th ed., Philadelphia, WB Saunders. 2372-2373. Gero´nimo-Pardo M, Cuartero-del-Pozo AB, Jime´nez-Vizuete JM, et al. (2005): Clarithromycin-nifedipine interaction as possible cause of vasodilatory shock. Ann Pharmacother.39: 538–542 Ghannoum, M., Wiegand, T.J., Liu, K.D., et al. (2015): Extracorporeal treatment for theophylline poisoning: systematic review and recommendations from the EXTRIP work group. Clinical Toxicology. 53 (4): 215-229. Gibbs JP, Liacouras CA, Baldassano RN, et al. (1999): Up- regulation of glutathi-one S-transferase activity in enterocytes of young children. Drug Metab Dispos. 27 (12): 1466-1469. Giner, L., Guija, J. A., Root, et al. (2016): Nomenclature and Definition of Suicidal Behavior. In Understanding Suicide. Springer International Publishing. (pp. 3-17) Ginsberg GL, Foos BP & Firestone MP (2005): Review and analysis of inhalation dosimetry methods for application to children's risk assessment. J Toxicol Environ Health A 68: 573-615. Gomila, I., López-Corominas, V., Pellegrini, et al. (2016): Alimemazine poisoning as evidence of Munchausen syndrome by proxy: A pediatric case report. Forensic science international.266: e18- e22 Gong, L.; Stamer, U.M.; Tzvetkov, Altman, R. B., et al. (2014): Pharm GKB summary: tramadol pathway. Pharmacogenet Genomics. 24 (7): 374–380. Graham, G.G., Davies, M.J., Day, R.O., et al. (2013): The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology.21 (3): 201-232. Grond, S. & Sablotzki, A. (2004): Clinical Pharmacology of Tramadol. Clinical Pharmacokinetics. 43 (13): 879-923. Guengerich, F.P. (2003): Cytochromes P450, drugs, and diseases. Molecular interventions, 3 (4), 194.

177

REFERENCES

Gupta, S.K., Peshin, S.S., Srivastava, A., et al. (2003): A study of childhood poisoning at national poisons information centre, All India Institute of Medical Sciences, New Delhi. Journal of occupational health, 45 (3): 191-196. Gupte, G. L. (2016): Management of paracetamol overdose. Paediatrics and Child Health.26 (10): 459-463.

(H) Haig GM, Bockbrader HN, Wesche DL, et al. (2001): Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 41 (5): 507-514. Hakkola J, Pasanen M, Purkunen R, et al. (1994): Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochem Pharmacol 48: 59–64 Hall, W. & Solowij, N. (1998): Adverse effects of cannabis. THE LANCET. 352: 1611–1616. Hamdi, E.; Gawad, T.; Khoweiled, A. et al. (2013): Lifetime prevalence of alcohol and substance abuse in Egypt: a community survey. Substance Abuse. 34: 97–114. Hara, K.; Minami, K. & Sata T. (2005): The effects of Tramadol and its metabolite on glycine, gamma-aminobutyric acid, and N-methyl-D- aspartate receptors expressed in Xenopus oocytes. Anesthesia and Analgesia. 100 (5): 1400-1405. Hargrove VM & McCutcheon JR. (2008): Comparison of drug concentrations taken from clamped and unclamped vessels. J Anal Toxicol.32: 621–625. Hassan, B. A., & Siam, M. G. (2014): Patterns of acute poisoning in childhood in Zagazig, Egypt: an epidemiological study. International scholarly research notices, Article ID 245279; 1-5. Hassanian-Moghaddam H.; Farajidana, H.; Sarjami, S. et al. (2013): Tramadol-induced apnea. The American journal of emergency medicine. 31 (1): 26-31. Hawton K, Saunders KE & O'Connor RC. (2012b): Self-harm and suicide in adolescents. Lancet. 379: 2373e82.

178

REFERENCES

Hegazy, R., Almalki, W. H., & Afify, R. H. M. (2012): Pattern of acute poisoning in Makkah region Saudi Arabia. The Egyptian journal of community medicine, 30 (1): 21- 37 Hermanns-Clausen, M.; Kneisel, S.; Szabo, B. et al. (2013): Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction. 108 (3): 534-44. Hetterich, N., Lauterbach, E., Stürer, A., et al. (2014): Toxicity of anti-hypertensives in unintentional poisoning of young children. The Journal of emergency medicine.47 (2): 155-162. Hines RN. (2007): Ontogeny of human hepatic cytochromes P450. J Biochem Mol Toxicol. 21 (4): 169-175. Hines RN. (2008): The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacol Ther. 2: 250–267 Hoffman, R.S. (2006): Opioids. In Goldfrank's manual of Toxicologic Emergencies. Nelson, L.S.; Howland, M.A.; Lewin, N.E.; Flomenbaum, N.E.; Lewis, N.A.; Goldfrank, L.R. (eds.), 8th ed. New York, McGraw-Hill. PP: 327-328. Holley, D. (2017): Glossary. In: General Biology I: Molecules, Cells and Genes Indiana, Dog Ear publishing, p. 365 Hore, P.; Robson, M. & Freeman, N. (2005): Chlorpyrifos accumulation patterns for child-accessible surfaces and objects and urinary metabolite excretion by children for 2 weeks after crack- and- crevice application. Environ. Health Perspect. 113 (2): 211–219. Huang, N.C., Lin, S.L., Hung, Y.M., et al. (2003): Severity assessment in acute paraquat poisoning by analysis of APACHE II score. Journal of the Formosan Medical Association, Taiwan yizhi, 102 (11), 782-787. Hyder AA, Wali S, Fishman S, et al. (2008): The burden of unintentional injuries among the under-five population in South Asia. Acta Paediatrica. 97: 267-75.

(I) Ingelman-Sundberg M. (2005): Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 5: 6–13.

179

REFERENCES

(J) Jacqz-Aigrain E, Funck-Brentano C & Cresteil T. (2003): CYP2D6 and CYP3A-dependent metabolism of dextromethorphan in humans. Pharmacogenetics 3: 197–204. James, R.; Roberts.J., Catherine, J., et al. (2012): Pesticide Exposure in Children, Pediatric and Council On Environmental Health, J. Peds., (2): 27-58. Jayashree, M. & Singhi, S. (2011): “Changing trends and predictors of outcome in patients with acute poisoning admitted to the intensive care.” J. Trop. Pediatr., 57 (5): 340-346. Jensen, H.K.; Konradsen, F.; Jørs, E.; et al. (2010): “Pesticide Use and Self-Reported Symptoms of Acute Pesticide Poisoning among Aquatic Farmers in Phnom Penh, Cambodia, J. Toxicol., 5: 25-32. Jepsen, F., & Ryan, M. (2005): Poisoning in children. Current Paediatrics, 15 (7); 563-568. Jesslin J, Adepu R & Churi S (2010): Assessment of prevalence and mortality incidences due to poisoning in a South Indian tertiary care teaching hospital. Indian J Pharm Sci 72: 587-91. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. (2002): Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther. 71: 21–29 Johnsrud EK, Koukouritaki SB, Divakaran K, et al. (2003): Human hepatic CYP2E1 expression during development. J Pharmacol Exp Ther. 307: 402–407. Jokanović, M. & Prostran, M. (2009): Pyridinium oximes as cholinesterase reactivators. Structure–activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr. Med. Chem., 16: 2177–2188. Jokanović, M. (2009): Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol. Lett., 190: 107– 115. Jokanovic, M.; Stukalov, P.V. & Kosanovic, M. (2002): Organophosphate induced delayed polyneuropathy. Curr Drug Targets CNS Neurol. Disord ., 1: 593–602.

180

REFERENCES

Joshi, P., & Ross, M. P. (2017): Intensive Care of Pediatric Poisoning Cases. Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient, Springer.10; 205-222. Juris E. (2006): Personal communication. Washington, DC: American Association of Poison Control Centers.

(K) Kaess M, Parzer P, Haffner J, et al. (2011): Explaining gender differences in non-fatal suicidal behavior among adolescents: a population-based study. BMC Public Health. 11: 597–603.21. Kalamaridis D. & DiLoreto K. (2014): Drug Partition in Red Blood Cells. In: Caldwell G., Yan Z. (eds.) Optimization in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ Karhu, D.; El-Jammal, A.; Dupain, T. et al. (2007): Pharmaco- kinetics and dose proportionality of three Tramadol Contramid OAD tablet strengths. Biopharmaceutics and Drug Disposition.28 (6): 323- 330. Kearns, G.L.; Abdel-Rahman, S.M.; Alander, et al. (2003): Developmental pharmacology–drug disposition, action, and therapy in infants and children. N. Engl. J. Med. 349: 1157-1167 Kholi U & Kuttiat VS (2008): Profile of childhood poisoning at a tertiary care centre in north India. Indian J Pedia. 75: 791-4. Kiang TK, Ensom MH & Chang TK. (2005): UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther.106: 97–132. Kigawa G, Nakano H, Kumada K, et al. (2000): Improvement of portal flow and hepatic microcirculatory tissue flow with N-acetylcysteine in dogs with obstructive jaundice produced by bile duct ligation. Eur J Surg .166: 77–84 Kim, Y. H., Yeo, J. H., Kang, M. J., et al. (2013): Performance assessment of the SOFA, APACHE II scoring system, and SAPS II in intensive care unit organophosphate poisoned patients. Journal of Korean medical science, 28 (12), 1822-1826. Kintz P, Evans J, Villain M, et al. (2010): Interpretation of hair findings in children after methadone poisoning. Forensic Sci Int 196: 51–54

181

REFERENCES

Kitson, R. & Carr, B. (2005): Tramadol and severe serotonin syndrome. Anaesthesia. 60 (9): 934-935. Kleinschmidt, K.C.; Wainscott, M. and Ford, M.D. (2001): Opioid In Clinical Toxicology. Ford, M.D.; Delaney, K. A.; Ling, L.J. and Erickson, T. (eds.), 1st edition. W. B. Saunders Company, USA. PP: 1758-1762. Knaggs, R.D.; Crighton, I.M.; Cobby, T.F. et al. (2004): The pupillary effects of intravenous morphine, codeine, and Tramadol in volunteers, Anesthesia & Analgesia. 99 (1): 108-112. Kohli, U., Kuttiat, V. S., Lodha, R., et al. (2008): Profile of childhood poisoning at a tertiary care centre in North India. The Indian Journal of Pediatrics, 75 (8); 791. Koren G. (1997): Therapeutic drug monitoring principles in the neonate. National Academy of Clinical Biochemistry. Clin Chem 43: 222–227. Koukouritaki SB, Manro JR, Marsh SA, et al. (2004): Developmental expression of human hepatic CYP2C9 and CYP2C19. J Pharmacol Exp Ther 308: 965–974 Koukouritaki SB, Simpson P, Yeung CK, et al. (2002): Human hepatic flavin-containing monooxygenases-1 (FMO1) and 3 (FMO3) developmental expression. Pediatr Res 51: 236–243. Kozer, E., & Koren, G. (2001): Management of paracetamol overdose. Drug safety. 24 (7): 503-512. Krueger SK & Williams DE. (2005): Mammalian flavin-containing monooxygenases: Structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol Ther 106: 357– 387. Kwong, T.C. (2002): Organophosphate pesticides: biochemistry and clinical toxicology. Ther. Drug Monit . 24: 144–149.

(L) Lahti, A., Harju, A., Hakko, H., et al. (2014): Suicide in children and young adolescents: a 25-year database on suicides from Northern Finland. Journal of psychiatric research.58: 123-128. Lam LT. (2003): Childhood and adolescence poisoning in NSW, Australia: an analysis of age, sex, geographic, and poison types. Inj Prev. 9: 338-42.

182

REFERENCES

Larson, A. M., Polson, J., Fontana, et al. (2005): Acetaminophen- induced acute liver failure: results of a United States multicenter, prospective study. Hepatology.42 (6): 1364-1372. Leikin JB & Watson WA. (2003): Post-mortem toxicology: what the dead can and cannot tell us. J Toxicol Clin Toxicol .41: 47–56 Leppert, W. and Luczak, J. (2005): The role of Tramadol in cancer pain treatment. Support Care Cancer. 13: 5-17. Lerman J. (1992): Pharmacology of inhalational anaesthetics in infants and children. Paediatr Anaesth. 2: 191–203. Levine, B. (2009): Postmortem forensic toxicology. In Principles of forensic toxicology . AACC Press, Washington, DC (pp. 3-13). Levine, B. (Ed.). (2003): Principles of forensic toxicology. Amer. Assoc. for Clinical Chemistry. Lifshitz, M., Sofer, S., & Gorodischer, R. (2003): Hydrocarbon poisoning in children: a 5-year retrospective study. Wilderness & environmental Medicine.14 (2): 78-82. Linden CH & Lovejoy FH. (1998): Poisoning and drug over dosage: Hasselbacher (editors), Harrison's Principles of internal medicine. 14th ed, New York, McGraw-Hill, 2535. Lowry JA, Jarrett RV, Wasserman G, et al. (2001): Theophylline toxicokinetics in premature newborns. Arch Pediatr Adolesc Med.155: 934–939. Lu, H., & Rosenbaum, S. (2014): Developmental pharmacokinetics in pediatric populations. The Journal of Pediatric Pharmacology and Therapeutics, 19 (4); 262-276.

(M) Mahdi, B.M. & Kia, B.M. (2008): Neurotoxic Disorders of Organo- phosphorus Compounds and Their Managements. Arch. Iranian Med., 11 (1): 65 – 89. Mahmood, I. (2016): Developmental pharmacology: impact on pharmacokinetics and pharmacodynamics of drugs. In Fundamentals of Pediatric Drug Dosing Springer International Publishing. (pp. 23-44).

183

REFERENCES

Maklad AIA & El-Saleet GMA. (1999): Acute non-insecticidal poisoning in children admitted at Tanta University Hospital and El- Menshawy General Hospital during the year (1998). Proc. 14th Annual Conf. Tanta Faculty Of Medicine On Medicine Into The Next Century, Tanta. 7-9: 1-7. Malla T, Malla KK, Gauchan E, et al. (2011): A scenario of poisoning in Children in Manial Teaching Hospital. J Nepal Paediatr Soc. 31 (2): 83-8. Manikyamba, D., & Madhavi, N. (2015). Clinical profile of poisoning in children admitted in a tertiary care centre. Int J Sci Res, .4 (2): 975-8. Marquardt, K. A.; Alsop, J. A. & Timothy, E. (2005): Tramadol Exposures Reported to Statewide Poison Control System. Albertson Ann Pharmacother. 39: 1039-1044. Matalová, P., Urbánek, K., & Anzenbacher, P. (2016): Specific features of pharmacokinetics in children. Drug metabolism reviews, 48 (1); 70-79. Maurer, H. H. (2007): Current role of liquid chromatography–mass spectrometry in clinical and forensic toxicology. Analytical and bioanalytical chemistry, 388 (7), 1315-1325. May T, Jurgens U, Rambrek B, et al. (1999): Comparison between pre-mortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy. Epilepsy Res. 33: 57–65. Mazor, S.S.; Feldman, K.W.; Sugar, N.F. et al. (2008): Pediatric tramadol ingestion resulting in seizure like activity: a case series Pediatric Emergency Care. 24 (6): 380-381. McCarver DG & Hines RN. (2002): The ontogeny of human drug- metabolizing enzymes: Phase II conjugation enzymes and regulatory mechanisms. J Pharmacol Exp Ther 300: 361–366. McFarland, S.E., Bronstein, A.C., Banerji, et al. (2017): Comparison of the Poisoning Severity Score and National Poison Data System schemes for the severity assessment of animal poisonings: a pilot study. Clinical toxicology, 55 (7), 629-635. McGrath KK & Jenkins AJ. (2009): Detection of drugs of forensic importance in postmortem bone. Am J Forensic Med Pathol. 30: 40–4.

184

REFERENCES

McGregor T, Parkar M & Rao S (2009): Evaluation and management of common childhood poisonings. Am Fam Physician. P397–403. Meistelman, C.; Benhamou, D.; Barre, J.; et al. (1990): Effects of age on plasma protein binding of sufentanil. Anesthesiology. 72: 470- 473. Meredith T. (1999): Epidemiology of poisoning. Medicine.27: 1–3. Mesbah, H. (2014): Reporting on Suicide in the Egyptian Press: Did the Arab Spring Make a Difference?. GSTF Journal on Media & Communications (JMC), 1 (2). Michael S.T & Michele M.B. (2017): The Poisoned Pediatric Patient Pediatrics in Review, 38 (5): p 207-218. Miki Y, Suzuki T, Tazawa C, et al. (2005): Steroid and xenobiotic receptor (SXR), cytochrome P450 3A4 and multidrug resistance gene 1 in human adult and fetal tissues. Mol Cell Endocrinol. 231 (1-2): 75- 85. Miller, C.K., Rutter, M.J., von Allmen, D., et al. (2016): Swallowing dynamics status post caustic ingestion in a pediatric patient: A multidisciplinary case report. International journal of pediatric otorhinolaryngology, 86, 4-8. Health Org 2009; 87 (12): 950-4. Moller SE, Larsen F, Pitsiu M., et al. (2000): Effect of citalopram on plasma levels of oral theophylline. Clin Ther.22: 1494–1501. Morikawa N, Honna T, Kuroda T, et al. (2008): High dose intravenous methylprednisolone resolves esophageal stricture resistant to balloon dilatation with intralesional injection of dexamethasone. Pediatr Surg Int. 24 (10): 1161-4. Mowry, J.B., Spyker, D.A., Brooks, D.E., McMillan, N., & Schauben, J.L. (2015): 2014 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report. Clinical toxicology, 53 (10), 962-1147. Mowry, J.B., Spyker, D. A., Cantilena Jr, L. R., McMillan, N., & Ford, et al. (2014): 2013 annual report of the American Association of poison Control Centers’ National Poison Data System (NPDS): 31st Annual Report, ” Clinical Toxicology.. 52 (10): 1032–1283

185

REFERENCES

Murphy SA, Johnson LC, Wu L, et al. (2003): Bereaved parents’ outcomes 4 to 60 months after their children’s deaths by accident, suicide, or homicide: a comparative study demonstrating differences. Death Stud. 27 (1): 39-61. Mutlu M, Cansu A & Karakas T. (2010): Pattern of pediatric poisoning in the east Karadeniz region between 2002–2006: increased suicide poisoning. Hum Exp Toxicol. 29 (2): 131.

(N) Naik RR, & Vadivelan M. (2012): Corrosive Poisoning. Indian J Clinic Pract 23: 131-34. Nakamura K, Yokoi T, Inoue K, et al. (1996): CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics 5: 449–457 Narayan Reddy KS. (2000): Toxicology. In: Narayan Reddy KS (ed). The synopsis of forensic medicine and toxicology. 14th Edn. Hyderabad. Medical Book Company. 221-293. Narayan Reddy KS. (2008): The essential of Forensic Medicine and Toxicology, 27th edition, Medical Book Company. 95: 440-456.

(O) Olguin HJ, Garduño LB, Pérez JF, et al. (2011): Frequency of suicide attempts by ingestion of drugs seen at a tertiary care pediatric hospital in Mexico. J Popul Ther Clin Pharmacol 18: e161-5. Osaghee DO & Sule G. (2013): Socio-demographic factors in accidental poisoning in children. Journal of Medicine and Medical Sciences. 4 (1): 13-6.

(P) Pach J, Persson H, Sancewicz-Pach K, et al. (1999): Comparison between the poisoning severity score and specific grading scales used at the Department of Clinical Toxicology in Krakow. Przegl Lek.56 (6): 401–8.

186

REFERENCES

Park KS. (2014): Evaluation and management of caustic injuries from ingestion of Acid or alkaline substances. Clin Endosc .47 (4): 301-7. Patton GC, Coffey C, Sawyer SM, et al. (2009): Global patterns of mortality in young people: a systematic analysis of population health data.Lancet.374: 881e92 Pawar, S.N.; Jangame C.M., & S.S. Mulaje (2015): Formulation & Evaluation of Tramadol Hydrochloride Sustained Release Matrix Tablets by Using Natural Polymers. World Journal of Pharmacy and Pharmaceutical Sciences. 4 (6): 1564-1573. Péry, A.R., Brochot, C., Zeman, et al. (2013): Prediction of dose- hepatotoxic response in humans based on toxicokinetic/toxicodynamic modeling with or without in vivo data: A case study with acetaminophen. Toxicology letters, 220 (1): 26-34. Peter J.B (2010): Theophylline. Pharmaceuticals, 3 (3): 725-747 Peter, J.V., Sudarsan, T.I., & Moran, J.L. (2014): Clinical features of organophosphate poisoning: A review of different classification systems and approaches. Indian Journal of Critical Care Medicine: Peer-Reviewed, Official Publication of Indian Society of Critical Care Medicine, 18 (11), 735. Poinern G.E.J., Brundavanam S & Fawcett D. (2012): "Biomedical Magnesium Alloys: A Review of Material Properties, Surface Modifications and Potential as a Biodegradable Orthopaedic Implant", American Journal of Biomedical Engineering. 2 (6): 218-240 Poklis, A. (2001): Analytic/forensic toxicology. Casarett and Doull’s toxicology, the basic science of poisons, 1089-1108. Pooni, P. A., & Bansal, V. (2016): Management of Poisonings in Children. Journal of Pediatric Critical Care, 84.

(R) Raffa, R.B.; Wu, C.; Stone, D.J. et al. (2000): Determination of the adsorption of tramadol hydrochloride by activated charcoal in-vitro and in-vivo. Journal of Pharmacological and Toxicological Methods. 43 (3): 205-210. Raghavendra, R., Kokatanur, C. M., Havanur, B., et al. (2017): Comprehensive Analysis of Fatal Poisoning Cases: An Autopsy Study. Indian Journal of Forensic Medicine & Toxicology, 11 (2); 181-185.

187

REFERENCES

Rahimi, H.R.; Soltaninejad, K & Shadnia, S. (2014): Acute tramadol poisoning and its clinical and laboratory findings. J Res Med Sci. 19 (9): 855–859. Ramasamy K & Gumaste VV. (2003): Corrosive ingestion in adults. J ClinGastroenterol.37 (2): 119–24. Rehni, A.K.; Singh, I.; & Kumar, M. (2008): Tramadol-Induced Seizurogenic Effect: A Possible Role of Opioid-Dependent Gamma Aminobutyric Acid Inhibitory Pathway. Basic & Clinical Pharmacology & Toxicology, 103: 262-266. Richardson T. (2000): Pitfalls in forensic toxicology. Ann ClinBiochem.37: 20–44. Ring JA, Ghabrial H, Ching MS, et al. (1999): Fetal hepatic drug elimination. Pharmacol Ther 84: 429–445 Riordan, M., Rylance, G., & Berry, K. (2002): Poisoning in children 5: rare and dangerous poisons. Archives of disease in childhood.87 (5): 407-410. Rivera, W; Gracia R. and Velez L.I. (2003): Central Nervous System Manifestations of Drug Toxicity, AHD media https: //www.ahcmedia.com/articles/21748-central-nervous-system- manifestations-of-drug-toxicity Robson, P. (2001): Therapeutic aspects of cannabis and cannabinoids. Br. J. Psychiatry. 178: 107-115. Ron Marczyk (2013): Worth Repeating: Scientific Studies Show Cannabis Is Medicine available on Rosenbaum SE. (2011): Basic Pharmacokinetics and Pharmaco- dynamics: An Integrated Textbook and Computer Simulations. Hoboken, NJ: John Wiley & Sons. Rosman, Y.; Makarovsky, I.; Bentur, Y.; et al. (2009): “Carbamate poisoning: treatment recommendations in the setting of a mass casualties event.”, Am. J. Emerg. Med.27: 1117-1124. Routledge, P.A. (1994): Pharmacokinetics in children. J. Antimicrob. Chemother. 34 (Suppl. A): 19-24.

188

REFERENCES

(S) Saadeh R. & Klaunig J. (2014): Childs Development and Respiratory System Toxicity Journal of Environmental & Analytical Toxicology. 4 (5); 1-8. Sahin S, Carman KB & Dinleyici C. (2011): Acute poisoning in children; Data of a Emergency Unit. Iranian journal of pediatrics. 21 (4): 479-84. Sam, K. G., Kondabolu, K., Pati, D., et al. (2009): Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning. Journal of forensic and legal medicine.16 (5): 239-247. Sandritter, L.; McLaughlin, M.; Artman M.; et al. (2017): The Interplay between Pharmacokinetics and Pharmacodynamics Pediatrics in Review.38: 195 Santoso, M. (2016): Islamic perspective on the rights of child : their consequences for the roles of state and civil society (especially in education), 2 (1); 18-25. Selcen, D.; Fukuda, T.; Shen, et al. (2004): Are MuSK antibodies the primary cause of myasthenic symptoms? Neurology.62: 1945–1950. Seyberth HW, Rane A, & Schwab M. (2011): Pediatric clinical pharmacology. Heidelberg, Germany Springer Seymour, F. K., & Henry, J. A. (2001): Assessment and management of acute poisoning by petroleum products. Human & experimental toxicology.20 (11): 551-562 Shadnia, S.; Brent, J.; Mousavi-Fatemi, K. et al. (2012): Recurrent Seizures in Tramadol Intoxication: Implications for Therapy Based on 100 Patients. Basic & Clinical Pharmacology & Toxicology. 111: 133- 136. Shaffer, D.R., & Kipp, K. (2013): Introduction to developmental psychology and its research strategies. Developmental psychology: Childhood and adolescence. 9th edition. Cengage Learning pp 4- 10. Sheemona, C.; Rajasri, B. & Dibyajyoti, B. (2014): Acute organophosphorus poisoning . Clinica Chimica Acta., 431: 66–76.

189

REFERENCES

Shiraishi, M.; Minami, K.; Uezono, Y. et al. (2002): Inhibitory effects of Tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing α7receptors. British Journal of Pharmacology. 136: 207-216. Shotar AM. (2005): Kerosene poisoning in children: A 6 year prospective study at the Princess Rahmat Teaching Hospital. Neuroendocrinology Letters. 26 (6): 835-8. Shou M, Korzekwa KR, Crespi CL, et al. (1994): The role of 12 cDNA-expressed human, rodent, and rabbit cytochromes P450 in the metabolism of benzo[a]pyrene and benzo[a]pyrene trans-7,8- dihydrodiol. Mol Carcinog 10: 159–168 Shub MD. (2015): Therapy of caustic ingestion: new treatment considerations. Curr Opin Pediatr .27 (5): 609-13. Singh M. (2007): Medical emergencies in children.4thed. New Delhi: Sagar. Singh, S. and Sharma, N. (2000): Neurological syndromes following organophosphate poisoning. Neurol. India., 48: 308–313. Skopp G. (2004): Preanalytic aspects in post-mortem toxicology. Forensic Sci Int. 142: 75–100. Sneitz N, Court MH, Zhang X, et al. (2009): Human UDP- glucuronosyl-transferase UGT2A2: cDNA construction, expression, and functional characterization in comparison with UGT2A1 and UGT2A3. Pharmacogenet Genomics 19: 923– 934. Sonnier M. & Cresteil T. (1998): Delayed ontogenesis of CYP1A2 in the human liver. Eur J Biochem 251: 893–898 Soori H (2001): Developmental Risk Factors for Unintentional Childhood Poisoning, Saudi Med J; Vol. 22 (3): 227-230. Sowmya, S.G., Avabratha, S., Varghese, et al. (2014): Poisoning in children: experience at a tertiary care hospital in Mangalore. Shock. 1: 1-8. Srinivasa, B.S., Manuprakash, S.K., Ara, S.S., et al. (2016): Socio- demographic profile of poisoning in children admitted to a tertiary hospital. Indian Journal of Child Health, 3 (3): 238-240. Stamer UM & Stu¨ber F. (2007): Codeine and tramadol analgesic efficacy and respiratory effects are influenced by CYP2D6 genotype. Anaesthesia 62: 1294–1295.

190

REFERENCES

Stephenson, T. (2005): How children's responses to drugs differ from adults Br J Clin Pharmacol. 59 (6): 670–673 Strolin Benedetti, M.; Whomsley, R. & Baltes, E.L. (2005): Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin. Drug Metab. Toxicol.1: 447-471. Sumpter A & Anderson BJ. (2009): Pediatric pharmacology in the first year of life. Curr Opin Anaesthesiol.22 (4): 469-475.

(T) Taheri, A., & Fard, A. S. (2015): A comparative study of children's rights from the perspective of Quran and the CRC.WALIA journal 31 (S2): 37-42. Takahashi H, Ishikawa S, Nomoto S, et al. (2000): Developmental changes in pharmacokinetics and pharmacodynamics of warfarin enantiomers in Japanese children.. Clin Pharmacol Ther. 68 (5): 541- 55. Tashakori, A. & Afshari, R. (2010): Tramadol overdose as a cause of serotonin syndrome: a case series. Clinical Toxicology. 48: 337-341. Tassaneeyakul W, Mohamed Z, Birkett DJ, et al. (1992): Caffeine as a probe for human cytochromes P450: Validation using cDNA- expression, immunoinhibition and microsomal kinetic and inhibitor techniques. Pharmacogenetics 2: 173–18 Tetelbaum M, Finkelstein Y, Nava-Ocampo AA, et al. (2005): Back to basics: understanding drugs in children: pharmacokinetic maturation. Pediatr Rev. 26 (9): 321-328. Thalhammer GH, Eber E & Zach MS. (2005): Pneumonitis and pneumatoceles following accidental hydrocarbon aspiration in children. Wien Klein Wochenschr 117: 150-153. Tovar, R., & Leikin, J.B. (2015): Irritants and corrosives. Emergency Medicine Clinics 33 (1): 117-131. Trangadia M, Kharadi R & Gupta BD (2016): Epidemiologic Study of Fatal and Non-Fatal Poisoning Case in Pediatric, Around Jamnagar Region, Gujarat in India (January-December 2013)International Journal of Medical Toxicology and Forensic Medicine. 6 (3): 128-134.

191

REFERENCES

Turner AR & Agrawal S. (2017): Toxicity, Marijuana. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 Jun-. Available from: https: //www.ncbi.nlm.nih.gov/books/NBK430823

(U) Urganci N, Usta M, Kalyoncu D, et al. (2014): Corrosive substance ingestion in children. Indian JPediatr.81 (7): 675-9.

(V) Vajda, F. (2014): Epilepsy: Effects of exposure to antiepileptic drugs during development. Nature Reviews Neurology.10 (1): 11-12. Van den Anker JN, Schoemaker RC, Hop WC, et al. (1995): Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age. Clin Pharmacol Ther 58: 650–659 van der Schans, M.J.; Lander, B.J.; Wiel, H.; et al. (2003): Toxicokinetics of the nerve agent (±) VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration. Toxicol. Appl. Pharmacol., 191: 48-62. Vargas-Bernal, R., Rodríguez-Miranda, E., & Herrera-Pérez, G. (2012): Evolution and expectations of enzymatic biosensors for pesticides. In Pesticides-Advances in Chemical and Botanical Pesticides. In Tech. Velez, L.I., Shepherd, J.G., Goto, C.S., et al. (2012): Approach to the child with occult toxic exposure. Up To Date ONLINE, 15. Vichova P & Jahodar L. (2003): Plant poisonings in children in the Czech Republic, 1996–2001. Hum Exp Toxicol.22 (9): 467–72. Vranković J. (2016): Age Related Changes in Antioxidant and Glutathione S Transferase Enzyme Activities in the Asian Clam, Biochemistry (Moscow). 81 (3), 224-232.

(W) Williams, R.H., & Erickson, T. (2015): Evaluating digoxin and theophylline intoxication in the emergency setting. Laboratory Medicine.29 (3): 158-162.

192

REFERENCES

Wu p., Hoven, C.W., Liu, X., et al. (2004): Substance Use, Suicidal Ideation and Attempts in Children and Adolescents Suicide and Life- Threatening Behavior .34 (4) : 408-421 Wu, W.N.; McKown, L.A., & Liao, S. (2002): Metabolism of the analgesic drug ULTRAM (tramadol hydrochloride) in humans: API- MS and MS/MS characterization of metabolites. Xenobiotica. 32 (5): 411-425.

(Y) Yang, C.C. & Deng, J.F. (2007): Intermediate syndrome following organophosphate insecticide poisoning. J. Chin. Med. Assoc.70: 467– 472. Yeung CK, Lang DH, Thummel KE, et al. (2000): Immuno- quantitation of FMO1 in human liver, kidney, and intestine. Drug Metab Dispos 28: 1107–1111 Yim EY, Kang HR, Jung JW, et al. (2013): CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics. Asia Pac Allergy. 3: 231–240 Yokoi T. (2009): Essentials for starting a pediatric clinical study (1): Pharmacokinetics in children. J Toxicol Sci 34: P307– SP312 Yoon Y, Park HD, Park KU., et al. (2006): Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/ theophylline ratios. Eur J Clin Pharmacol. 62: 627–631. Young, J.C., & Widom, C.S. (2014): Long-term effects of child abuse and neglect on emotion processing in adulthood. Child abuse & Neglect. 38 (8): 1369-1381. Yu, J. H., Weng, Y. M., Chen, K. F., et al. (2012): Triage vital signs predict in-hospital mortality among emergency department patients with acute poisoning: a case control study. BMC health services research, 12 (1), 262.

(Z) Zanger UM & Schwab M. (2013): Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther.138: 103–141

193

REFERENCES

Zarezadeh, M., & Bahrampour, A. (2011): Poisoning Survey of Referred Children to Afzalipour Hospital in Kerman in 2009-2010. Iranian Journal of Toxicology, 4 (4); 397-401. Zisowsky, J.; Krause, A. & Dingemanse, J. (2010): Drug Development for Pediatric Populations: Regulatory Aspects. Pharmaceutics. 2: 364-388.

194

APPENDICES

APPENDIX I

195

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

ﻳﻌﺪ اﻟﺘﺴﻤﻢ ﺣﺎﻟﺔ ﻃﻮارئ هﺎﻣﺔ وﻣﺸﻜﻠﺔ آﺒﻴﺮة ﻓﻲ اﻟﻔﺌﺎت اﻟﻌﻤﺮﻳﺔ ﻟﻸﻃﻔﺎل ﻓﻲ ﺟﻤﻴﻊ أﻧﺤﺎء اﻟﻌﺎﻟﻢ . ﺗﺘﻨﻮع أﺳﺒﺎب اﻟﺘﺴﻤﻢ وأﻧﻮاﻋﻪ ﻓﻲ أﻧﺤﺎء ﻣﺨﺘﻠﻔﺔ ﻣﻦ اﻟﻌﺎﻟﻢ وداﺧﻞ اﻟﺒﻠﺪ ًأﻳﻀًﺎ ﺣﺴﺐ ﻋﻮاﻣﻞ ﻣﺜﻞ اﻟﺘﻌﻠﻴﻢ واﻟﺪﻳﻤﻮﻏﺮاﻓﻴﺎ واﻟﻌﻮاﻣﻞ اﻻﺟﺘﻤﺎﻋﻴﺔ- اﻻﻗﺘﺼﺎدﻳﺔ واﻟﻌﺎدات واﻟﻤﻌﺘﻘ ﺪات اﻟﻤﺤﻠﻴﺔ .

ﻳﺄﺗﻲ آﻞ ﻋﺎم ﻋﺪد آﺒﻴﺮ ﻣﻦ اﻟﻤﺮﺿﻰ ﺗﺤﺖ ﺳﻦ ﺳﺖ ﺳﻨﻮات إﻟﻰ ﻗﺴﻢ اﻟﻄﻮارئ ﻣﻊ أﻋﺮاض اﻟﺘﺴﻤﻢ . ً ﻓﺪاﺋﻤًﺎ ﻣﺎ ﻳﺤﺪث اﻟﺘﺴﻤﻢ اﻟﻌﺮﺿﻲ ﻟﻸﻃﻔﺎل دون ﺳﻦ اﻟﺨﺎﻣﺴﺔ . ﺑﻴﻨﻤﺎ ﻓﻲ اﻷﻃﻔﺎل اﻷآﺒﺮ ًﺳﻨًﺎ واﻟﻤﺮاهﻘﻴﻦ، ﺗﻜﻮن ﻣﺤﺎوﻻت اﻻﻧﺘﺤﺎر أآﺜﺮ ًﺷﻴﻮﻋًﺎ . وﻗﺪ ﻳﻨﺘﺞ اﻟﺘﺴﻤﻢ ﻣﻦ ﺑﻴﻜﺎ أو ﻋﻄﺶ أو ﺟﻮع . آﻤﺎ ﻗﺪ ﻳﻜﻮن هﺬا ﻣ ﻈ ﻬ ﺮ ًاً ﻣﻦ ﻣﻈﺎهﺮ اﻧﻌﺪام اﻷﻣﻦ ، أو ﻹﻳﺬاء اﻟﺬات ﻧﺘﻴﺠﺔ ﻟﻤﺸﺎﻋﺮ ﻣﺬﻧﺒﺔ أو ﺳﻠﻮك ﻳﺴﻌﻰ إﻟﻰ ﺟﺬب اﻻهﺘﻤﺎم .

آﺎن اﻟﺒﺤﺚ اﻟﺤﺎﻟﻲ ﻋﺒﺎرة ﻋﻦ دراﺳﺔ وﺻﻔﻴﺔ ﻣﺴﺘﻌﺮﺿﺔ ، ﺿﻤﺖ ﻣﺎﺋﺔ واﺛﻨﻴﻦ وﺧﻤﺴﻴﻦ ﻣﻦ اﻟﻤﺸﺎرآﻴﻦ اﻟﻤﺼﺮﻳﻴﻦ ﻣﻦ آﻼ اﻟﺠﻨﺴﻴﻦ ( ٩٦ أﻧﺜﻰ و ٥٦ ذآﻮر ).

ﺗﻢ ﺗﺼﻨﻴﻔﻬﻢ إﻟﻰ ٤ ﻓﺌﺎت ﻋﻤﺮﻳﺔ ؛ اﻷﻃﻔﺎل اﻟﺼﻐﺎر ( ١- < ٣ ﺳﻨﻮات ) ( ٤٤ ٪ ) ، اﻟﻄﻔﻮﻟﺔ اﻟﻤﺒﻜﺮة ( ٣- ٩ ﺳﻨﻮات ) ( ١٤ ٪ ) ، ﻣﺮﺣﻠﺔ اﻟﻄﻔﻮﻟﺔ اﻟﻤﺘﺄﺧﺮة ( ٩- < ١٣ ﺳﻨﺔ ) ( ٧ ٪ ) واﻟﻤﺮاهﻖ ﻳﻦ ( ١٣- < ١٨ ً ﻋﺎﻣًﺎ ) ( ٣٥ ٪ ). ﺑﻴﻨﻤﺎ وﻓﻘﺎ ﻟﻄﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ، ﺗﻢ ﺗﺼﻨﻴﻔﻬﺎ ﻓﻲ ﻣﺠﻤﻮﻋﺘﻴﻦ . ﻣﺠﻤﻮﻋﺔ ﺳﻤﻴﺔ ﻋﺮﺿﻴﺔ ( ﻏﻴﺮ ﻣﺘﻌﻤﺪة ) ( ١ ) وﺳﻤﻴﺔ اﻻﻧﺘﺤﺎر ( اﻟﻤﺠﻤﻮﻋﺔ ٢ ). وآﺎن ﻋﺪد ﺣﺎﻻت اﻟﺴﻤﻴﺔ اﻟﻌﺮﺿﻴﺔ ٨٩ ﺣﺎﻟﺔ ( ٥٨٫٦ ٪ ) ، ﻓﻲ ﺣﻴﻦ ﺑﻠﻎ ﻋﺪد ﺣﺎﻻت اﻟﺴﻤﻴﺔ اﻻﻧﺘﺤﺎرﻳﺔ ٦٣ ﺣﺎﻟﺔ ( ٤١٫٤ ٪ ).

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﻌﻤﺮ وﻃﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ، ﺣﻴﺚ آﺎن اﻷﻃﻔﺎل اﻟﺼﻐﺎر ( ١- < ٣ ﺳﻨﻮات ) ﻳﻤﺜﻠﻮن ﻏﺎﻟﺒﻴﺔ اﻟ ﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ اﻟﻤﺠﻤﻮﻋﺔ ١ ( ٧٥٫٣ ٪ ) ﻳﻠﻴﻬﺎ اﻟﻄﻔﻮﻟﺔ اﻟﻤﺒﻜﺮة ، ﻓﻲ ﺣﻴﻦ آﺎن ﻓﺘﺮة اﻟﻤﺮاهﻘﺔ ( ١٣- < ١٨ ﺳﻨﺔ ) ﻣﻤﺜﻠﺔ ﻏﺎﻟﺒﻴﺔ ﺣﺎﻻت اﻻﻧﺘﺤﺎر اﻟﻤﺠﻤﻮﻋﺔ ٢ ( ٨٤٫١ ٪ ).

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﻌﻤﺮ وﻧﻮع اﻟﺴﻤﻮم وﻣﻘﺪارهﺎ ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ آﺎﻧﺖ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، ﺣﻴﺚ ﻣﺜﻠﺖ اﻷدوﻳﺔ اﻟﺴﻤﻮم اﻟﺸﺎﺋ ﻌﺔ ﻓﻲ ﻣﺮﺣﻠﺔ اﻟﻄﻔﻮﻟﺔ اﻟﻤﺒﻜﺮة ( ٦٨٫٢ ٪ ) واﻟﻤﺮاهﻘﺔ ( ٥٨٫٥ ٪ ) واﻟﻄﻔﻮﻟﺔ اﻟﻤﺘﺄﺧﺮة ( ٨٠ ٪ )، ﺑﻴﻨﻤﺎ ﻓﻲ اﻷﻃﻔﺎل اﻟﺼﻐﺎر ﺗﻤﺜﻞ اﻷدوﻳﺔ واﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ اﻟﺴﻤﻮم اﻟﻤﺸﺘﺮآﺔ .

آﺎﻧﺖ اﻟﻌﻼﻗﺎت ﺑﻴﻦ اﻟﻌﻤﺮ وﺗﻮاﻓﺮ اﻟﺴﻢ وأهﻢ أﺳﺒﺎب اﻟﺴﻤﻴﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ، ﻓﻲ اﻟﻤﺠﻤﻮﻋﺔ ١، ﺑﻠﻎ ﻣﻌﻈﻢ اﻷﻃﻔﺎل اﻟﺼﻐﺎر اﻟﺴﻢ ﻓﻲ ﺳﻄﺢ ﻣﻨﺨﻔﺾ وآﺎن اﻟﺴﺒﺐ اﻷآﺜﺮ اﺣﺘﻤﺎﻟﻴﺔ ﻟﻠﺴﻤﻴﺔ ﺑﻴﻨﻬﻢ هﻮ اﻹهﻤﺎل ، ﻓﻲ ﺣﻴﻦ وﺻﻠﺖ ﻣﻌﻈﻢ اﻷﻃﻔﺎل إﻟﻰ اﻟﺴﻤﻮم ﻓﻲ اﻟﺤﺎوﻳﺎت اﻟﻤﻔﺘﻮح ة . وآﺎن اﻟﺴﺒﺐ اﻷآﺜﺮ اﺣﺘﻤﺎﻻ ﻟﻠﺴﻤﻴﺔ ﺑﻴﻨﻬﻢ هﻮ

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

اﻟﻔﻀﻮل . ﻓﻲ اﻟﻤﺠﻤﻮﻋﺔ اﻟﺜﺎﻧﻴﺔ أﺧﺬ ﻣﻌﻈﻢ اﻟﻤﺮاهﻘﻴﻦ واﻟﻄﻔﻮﻟﺔ اﻟﻤﺘﺄﺧﺮة ﻣﻦ ﻣﺮاﺣﻞ اﻟﻄﻔﻮ ﻟﺔ أدوﻳﺔ ﺁﺑﺎﺋﻬﻢ وآﺎن اﻟﺴﺒﺐ اﻷآﺜﺮ ﺷ ﻴ ﻮ ﻋ ﺎً ً ﻟﻠﺘﺴﻤﻢ ﺑﻴﻨﻬﻢ ﻣﺤﺎوﻟﺔ اﻻﻧﺘﺤﺎر ﻣﻦ اﻟﻤﺸﺎآﻞ اﻷﺳﺮﻳﺔ .

اﻟﺘﻮزﻳﻊ اﻟﻨﺴﺒﻲ ﻟﻠﻨﻮع ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ، ﺗﻤﺜﻞ اﻹﻧﺎث ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت اﻟﻤﺪروﺳﺔ ( ٦٣٫٢ ٪ ) ﻣﻘﺎرﻧﺔ ﺑﺎﻟﺬآﻮر اﻟﺬﻳﻦ ﻣﺜﻠﻮا ( ٣٦٫٨ ٪ ).

آﺎﻧﺖ اﻟﻤﻘﺎرﻧﺔ ﺑﻴﻦ اﻟﺠﻨﺲ وﻃﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ﻓﻲ اﻟﺪر اﺳﺔ اﻟﺤﺎﻟﻴﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، وآﺎﻧﺖ ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﻓﻲ ﻣﺠﻤﻮﻋﺔ اﻟﺴﻤﻴﺔ اﻟﻌﺮﺿﻴﺔ ١ ﻣﻦ اﻟﺬآﻮر ( ٥٣٫٩ ٪ )، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﻓﻲ اﻟﻤﺠﻤﻮﻋﺔ اﻟﺴﻤﻴﺔ اﻻﻧﺘﺤﺎرﻳﺔ ٢ آﺎﻧﺖ ﻣﻦ اﻹﻧﺎث ( ٨٧٫٣ ٪ ).

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﺠﻨﺲ و ( ﻧﻮع اﻟﺴﻢ وآﻤﻴﺘﻪ ) آﺎﻧﺖ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، أﺧﺬت ﻣﻌﻈﻢ اﻹﻧﺎث اﻷ دوﻳﺔ واﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ ﻓﻮق اﻟﺠﺮﻋﺔ اﻟﺴﺎﻣﺔ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ اﻟﺬآﻮر ﺗﻨﺎوﻟﻮا اﻷدوﻳﺔ ﺑﻜﻤﻴﺎت ﻣﺠﻬﻮﻟﺔ .

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﺠﻨﺲ واﻟﺴﺒﺐ اﻷآﺜﺮ ا ﺣ ﺘ ﻤ ﺎ ًﻻً ﻟﻠﺴﻤﻴﺔ ، ﺣﻴﺚ أن اﻟﺴﺒﺐ اﻷآﺜﺮ ﺷ ﻴ ﻮ ﻋ ًﺎً ﻟﻠﺘﺴﻤﻢ ﻟﺪى اﻟﺬآﻮر هﻮ اﻹهﻤﺎل ، ﻓﻲ ﺣﻴﻦ أن اﻟﺴﺒﺐ اﻷآﺜﺮ ا ﺣ ﺘ ﻤ ﺎ ﻻً ً ﻟﻠﺴﻤﻴﺔ ﻓﻲ اﻹﻧﺎث هﻮ اﻟ ﻤﺸﺎآﻞ اﻷﺳﺮﻳﺔ . ﻓﻲ ﺣﻴﻦ أن اﻻﺿﻄﺮاب اﻟﻨﻔﺴﻲ و اﻟﻤﺸﺎآﻞ اﻟﺪراﺳﻴﺔ واﻻﺿﻄﺮاب اﻟﻌﺎﻃﻔﻲ واﻷدوﻳﺔ اﻟﺨﺎﻃﺌﺔ آﺎﻧﺖ هﻲ اﻷﺧﺮى ﺳﺒﺐ ل ﻟﺴﻤﻴﺔ ﻓﻲ اﻷﻃﻔﺎل اﻹﻧﺎث ﻣﻘﺎرﻧﺔ ﻣﻊ اﻷﻃﻔﺎل اﻟﺬآﻮر .

ﺗﻮزﻳﻊ ﺣﺴﺐ اﻹﻗﺎﻣﺔ ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ، ﺟﺎءت اﻟﺤﺎﻻت ﻣﻦ اﻟﻤﻨﺎﻃﻖ اﻟﺮﻳﻔﻴﺔ ﻣﻤﺜﻠﺔ ( ٥٢ ٪ ) ، ﺑﻴﻨﻤﺎ ﺟﺎءت اﻟﺤﺎﻻت ﻣﻦ اﻟﻤﻨﺎﻃﻖ اﻟﺤﻀﺮﻳﺔ ﻣﻤﺜﻠﺔ ( ٤٨ ٪ ).

اﻹﻗﺎﻣﺔ وﻃﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ، ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ ﺟﺎءت ﻣﻦ اﻟﻤﻨﺎﻃﻖ اﻟﺮﻳﻔﻴﺔ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ ﺣﺎﻻت اﻻﻧﺘﺤﺎر ﺟﺎءت ﻣﻦ اﻟﻤﻨﺎﻃﻖ اﻟﺤﻀﺮﻳﺔ وأﻇﻬﺮت ﻋﻼﻗﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ﻣﻬﻤﺔ .

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻹﻗﺎﻣﺔ وﻧﻮع اﻟﺴﻢ آﺎﻧﺖ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﺮﻳﻔﻴﺔ أﺧﺬت ﻣﺒﻴﺪات اﻵﻓﺎت ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﺤﻀﺮﻳﺔ ﺗﻨﺎوﻟﺖ اﻷدوﻳﺔ . أﻳﻀﺎ ، ﺗﻢ اﻹﺑﻼغ ﻋﻦ ﻟﺪﻏﺔ اﻟﺜﻌﺎﺑﻴﻦ ﻓﻘﻂ ﻓﻲ اﻟﺤﺎﻻت اﻟﺮﻳﻔﻴﺔ .

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻹﻗﺎﻣﺔ واﻹﺳﻌﺎﻓﺎت اﻷوﻟﻴﺔ ، واﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻹﻗﺎﻣﺔ وﺳﺎﻋﺎت اﻟﺘﺄﺧﻴﺮ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، وﺗﻤﺖ ﻣﻌﻈﻢ اﻹﺳﻌﺎﻓﺎت اﻷوﻟﻴﺔ ﺑﻄﺮﻳﻘﺔ ﺧﺎﻃﺌﺔ ﻓﻲ اﻟﺤﺎﻟﺔ اﻟﺮﻳﻔﻴﺔ ، ﻓﻲ ﺣﻴﻦ أن اﻹﺳﻌﺎﻓﺎت اﻷوﻟﻴﺔ ﻟﻢ ﺗﺘﻢ ﻓﻲ اﻟﻤﻨﺎﻃﻖ اﻟﺤﻀﺮﻳﺔ .

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻹﻗﺎﻣﺔ ( و ﺗﻮاﻓﺮ اﻟﺴﻤﻮم وﺳﺒﺐ اﻟﺴﻤﻴﺔ اﻷآﺜﺮ ا ﺣ ﺘ ﻤ ﺎ ًﻻً ) آﺎﻧﺖ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﻓﻲ اﻟﻤﻨﺎﻃﻖ اﻟﺮﻳﻔﻴﺔ ﺣﺼﻠﺖ ﻋﻠﻰ اﻟﺴ ﻢ ﻣﻦ ﺳﻄﺢ ﻣﻨﺨﻔﺾ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﺤﻀﺮﻳﺔ ﺣﺼﻠﺖ ﻋﻠﻰ اﻟﺴﻢ اﻟﻤﺘﻮﻓﺮ وهﻮ ﻋﻼج واﻟﺪﻳﻬﻢ . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى ، ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ب اﻟﺴﺒﺐ اﻷآﺜﺮ ﻟﻠﺴﻤﻴﺔ ﺑﻴﻦ اﻟﺤﺎﻻت اﻟﺮﻳﻔﻴﺔ آﺎن اﻹهﻤﺎل ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ ﺑﻴﻦ اﻟﺤﺎﻻت اﻟﺤﻀﺮﻳﺔ اﻟﻤﺸﺎآﻞ اﻟﻌﺎﺋﻠﻴﺔ ﺗﻠﻴﻬﺎ اﻹهﻤﺎل .

اﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ ﻟﻠﺤﺎﻻت ﻓ ﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ، آﺎﻧﺖ ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت ﻓﻲ ﻣﺮﺣﻠﺔ ﻣﺎ ﻗﺒﻞ اﻟﻤﺪرﺳﺔ ( ﻋﻤﺮ اﻟﺤﻀﺎﻧﺔ ) ﺑﻨﺴﺒﺔ ( ٥٢٫٦ ٪ ) ﺗﻠﺘﻬﺎ اﻟﻤﺪرﺳﺔ اﻟﺜﺎﻧﻮﻳﺔ واﻹﻋﺪادﻳﺔ واﻻﺑﺘﺪاﺋﻴﺔ ﺑﻨﺴﺒﺔ ( ٢١٫٧ ٪ ) ، ( ١٥٫٨ ٪ )، ( ٧٫٩ ٪ ) و ( ٢ ٪ ) ﻋﻠﻰ اﻟﺘﻮاﻟﻲ . ﻓﻲ ﺣﻴﻦ أن اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻃﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ واﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ ﻟﻠﻤﺮﺿﻰ ، وﻣﻌﻈﻢ ا ﻟﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ ( اﻟﻤﺠﻤﻮﻋﺔ ١ ) آﺎﻧﺖ ﻓﻲ ﺳﻦ ﻣﺎ ﻗﺒﻞ اﻟﻤﺪرﺳﺔ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ ﺣﺎﻻت اﻻﻧﺘﺤﺎر ( اﻟﻤﺠﻤﻮﻋﺔ ٢ ) آﺎﻧﺖ ﻓﻲ اﻟﻤﺪرﺳﺔ اﻟﺜﺎﻧﻮﻳﺔ ﺗﻠﻴﻬﺎ اﻹﻋﺪادﻳﺔ .

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ وﻧﻮع وآﻤﻴﺔ اﻟﺴﻢ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ، وآﺎﻧﺖ اﻷدوﻳﺔ هﻲ ﺷﺎﺋﻌﺔ ﺑﻴﻦ ﻣﺮﺣﻠﺔ ﻣﺎ ﻗﺒﻞ اﻟﻤﺪرﺳﺔ ، ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ اﻟﻤﺒﻴﺪات هﻲ ًاﻟﺸﺎﺋﻌًﺔ ﺑﻴﻦ اﻟﺤﺎﻻت ﻏﻴﺮ اﻟﻤﺘﻌﻠﻤﺔ . ﻣﻌﻈﻢ ﺣﺎﻻت ﻣﺎ ﻗﺒﻞ اﻟﻤﺪرﺳﺔ وﻏﻴﺮ اﻟﻤﺘﻌﻠﻤﺔ أﺧﺬت آﻤﻴﺔ ﻏﻴﺮ ﻣﻌﺮوﻓﺔ ﻣﻦ اﻟﺴﻢ .

ﻣﻘﺎرﻧﺔ ﺑﻴﻦ اﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ واﻟﺴﺒﺐ اﻷآﺜﺮ اﺣﺘﻤﺎﻻ ﻟﻠﺴﻤﻴﺔ آﺎن ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، آﺎن اﻟﺴﺒﺐ اﻷآﺜﺮ اﺣﺘﻤﺎﻻ ﻓﻲ ﺣﺎﻻت ﻣﺎ ﻗﺒﻞ اﻟﻤﺪ رﺳﺔ هﻮ اﻹهﻤﺎل ، ﺑﻴﻨﻤﺎ ﻓﻲ اﻟﻤﺪرﺳﺔ اﻟﺜﺎﻧﻮﻳﺔ آﺎﻧﺖ اﻟﻤﺸﺎآﻞ اﻟﻌﺎﺋﻠﻴﺔ .

اﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ ﻵﺑﺎ ء اﻟﻤﺸﺎرآﻴﻦ ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﻴﺔ ، ﻟﻢ ﺗﻜﻦ ﻏﺎﻟﺒﻴﺔ ﺁﺑﺎ ئ هﻢ ّ ﻣﺘﻌﻠّﻤﻴﻦ وآﺎﻧﺖ ﻧﺴﺒﺔ اﻟﺘﻌﻠﻴﻢ اﻟﻤﻨﺨﻔﺾ ٥٠٫٦٪ ﻳﻠﻴﻬﺎ اﻟﺘﻌﻠﻴﻢ اﻟﻢ ﺗﻮﺳﻂ ٢٧ ٪ .

اﻟﻤﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ ﻷﻣﻬﺎت اﻟﺤﺎﻻت اﻟﻤﺸﺎرآﺔ ﻓﻲ اﻟﺪر اﺳﺔ اﻟﺤﺎﻟﻴﺔ ، ﻟﻢ ﺗﻜﻦ ﻏﺎﻟﺒﻴﺔ اﻷﻣﻬﺎت ﻣﺘﻌﻠﻤﺎت وﺗﻢ ﺗﻌﻠﻴﻤﻬﻦ ﺑﻨﺴﺒﺔ ﻣﻨﺨﻔﻀﺔ ﺑﻠﻐﺖ ٥١٫٦٪ ﺛﻢ اﻟﺘﻌﻠﻴﻢ اﻟﻌﺎﻟﻲ واﻟﺘﻌﻠﻴﻢ اﻟﻤﺘﻮﺳﻂ ﺑﻨﺴﺒﺔ ٢٧٫٩ ٪ و ٢٠٫٤ ٪ .

ﻣﻘﺎرﻧﺔ ﻣﻊ اﻟﻮﺿﻊ اﻟﻮﻇﻴﻔﻲ ﻟﻶﺑﺎء واﻷﻣﻬﺎت اﻟﻤﺸﺎرآﻴﻦ ﻓﻲ هﺬﻩ اﻟﺪراﺳﺔ ، آﺎن اﻵﺑﺎء ﻳﻌﻤﻠﻮن ﻓﻲ ٩٤٫٧ ٪ ﻣﻦ اﻟﺤﺎﻻت، ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ اﻷ ﻣﻬﺎت ﻳﻌﻤﻠﻦ ﻓﻲ ٣٠٫٢ ٪ .

اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻋﻤﻞ اﻟﻮاﻟﺪﻳﻦ واﻟﺘﻌﻠﻴﻢ وﻃﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ( ﻓﻲ آﻠﺘﺎ اﻟﻤﺠﻤﻮﻋﺘﻴﻦ ﺑﻬﺬا اﻟﺒﺤﺚ ) ، آﺎﻧﺖ هﻨﺎك ﻋﻼﻗﺎت ﻣﻬﻤﺔ . ﻓﻲ ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ ، آﺎن ﺁﺑﺎ ؤ هﻢ ﻳﻌﻤﻠﻮن وﻟﻴﺴﻮا ﻣﺘﻌﻠﻤﻴﻦ ، ﺑﻴﻨﻤﺎ ﻣﻌﻈﻢ ﺣﺎﻻت اﻻﻧﺘﺤﺎر ، آﺎن ﺁﺑﺎؤهﻢ ﻳﻌﻤﻠﻮن واﻟﺘﻌﻠﻴﻢ م ﺗﻮﺳﻂ . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى ، ﺗﺒﻴﻦ أن ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ آﺎﻧﺖ اﻷم رﺑﺔ ﻣﻨﺰل وﻏﻴﺮ ﻣﺘﻌﻠﻤﺔ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ ﺣﺎﻻت اﻻﻧﺘﺤﺎر ، آﺎﻧﺖ اﻷﻣﻬﺎت ( رﺑﺎت اﻟﺒﻴﻮت وﻏﻴﺮ ﻣﺘﻌﻠﻤﺎت ) و ( اﻟﻌﺎﻣﻼت وال م ﺗﻌﻠﻤﺎت ﺗﻌﻠﻴﻢ م ﺗﻮﺳﻂ ) ﻟﻬﻦ ﻧﻔﺲ اﻟﻨﺴﺒﺔ .

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻋﻤﻞ اﻷم واﻟﺘﻌﻠﻴﻢ وﺗﻮاﻓﺮ اﻟﺴﻢ ذات د ﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ . وﻗﺪ أﺧﺬت ﺣﺎﻻت اﻷم ( اﻟﻌﺎﻣﻠﺔ واﻟﻤﺘﻌﻠﻤﺔ ﺗ ﻌ ﻠ ﻴ ﻤ ًﺎً ﻋ ﺎ ﻟ ﻴ ًﺎً ) و ( اﻟﻌﺎﻣﻠﺔ واﻟﻤﺘﻌﻠﻤﺔ ال ﻣﺘﻮﺳﻂ ) أدوﻳﺔ ﺁﺑﺎﺋﻬﻢ ، ﻓﻲ ﺣﻴﻦ أن ﻣﻌﻈﻢ رﺑﺎت اﻟﺒﻴﻮت وغ اﻟﺒﻴﺔ ﺣﺎﻻت اﻷم اﻟﻤﺘﻌﻠﻤﺔ أﺧﺬت اﻟﺴﻤﻮم ﻣﻦ ﺳﻄﺢ ﻣﻨﺨﻔﺾ .

وﻣﻼﺣﻈﺔ أﺧﺮى ﻣﻘﺎرﻧﺔ ﺑﻴﻦ ﻋﻤﻞ ا ﻵﺑﺎ ء وا ﻟﺘﻌﻠﻴﻢ وا ﻟﺴﺒﺐ اﻷآﺜﺮ ا ﺤﺘﻤﻼً ﻟﻠﺴﻤﻴ ة، أن اﻹهﻤﺎل ﻓﻲ ﻣﻌﻈﻢ ﺣﺎﻻ ت ا ﻟﻌﻤﺎ ل و ﺘﻌﺬ ر اﻟﺘﻌﻠﻴﻢ أو ا ﻟﺘﻌﻠﻴﻢ ا ﻟﻤﻨﺨﻔﺾ هﻮ ا ﻟﺴﺒﺐ ا ﻷ آﺜﺮ ا ﺤﺘﻤﻼً ﻟﻠﺴﻤﻴﺔ . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى ، ﻓﺈن ﻣﻌﻈﻢ ﺣﺎﻻت رﺑﺎت اﻟﺒﻴﻮت وﻏﻴﺮ اﻟﻤﺘﻌﻠﻤﺎت أو اﻟﻤﺘﻌﻠﻤﺎت وﻳﻌﻤﻠﻦ ﺣﺘﻰ ﻣﻊ اﻟﺘﻌﻠﻴﻢ اﻟﻌﺎﻟﻲ آﺎن اﻹهﻤﺎل هﻮ اﻟﺴﺒﺐ اﻷآﺜﺮ ا ﺣ ﺘ ﻤ ﺎ ًﻻً ﻟﻠﺴﻤﻴﺔ .

اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻋﻤﻞ اﻟﻮاﻟ ﺪﻳﻦ واﻟﺘﻌﻠﻴﻢ و ( ﺳﺎﻋﺎت اﻟﺘﺄﺧﻴﺮ ) ، هﻨﺎك ﻋﻼﻗﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ﺑﻴﻦ اﻟﻌﻼﻗﺔ اﻹﻳﺠﺎﺑﻴﺔ ﺑﻴﻦ ﻋﻤﻞ اﻷب واﻟﺘﻌﻠﻴﻢ وﺳﺎﻋﺎت اﻟﺘﺄﺧﻴﺮ، وأﻳﻀﺎ ﺑﻴﻦ اﻟﻌﻤﻞ اﻷم واﻟﺘﻌﻠﻴﻢ وﺳﺎﻋﺎت اﻟﺘﺄﺧﻴﺮ .

ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ﺑﺘﻮاﻓﺮ اﻟﺴﻢ ، ﻓﺈن ﻣﻌﻈﻢ اﻟﺴﻤﻮم اﻟﻤﺘﺎﺣﺔ آﺎﻧﺖ ﻋﻠﻰ ﺳﻄﺢ ﻣﻨﺨﻔﺾ ( ٢٨٫٩ ٪ ).

وﻓﻘﺎ ﻟﻨﻮع اﻟﺴﻢ ، ﺗﺴﻤﻤﺖ ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﺑﺎﻷدوﻳﺔ ( ٥٢ ٪ ) ﻳﻠﻴﻬﺎ ﻣﺒﻴﺪ اﻵﻓﺎت ( ١٩ ٪ )، واﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ ( ١٧ ٪ ) ، واﻟﻤﺨﺪرات ( ١١ ٪ ) وﻋﻀﺔ اﻟﺜﻌﺎﺑﻴﻦ ( ١ ٪ )

وﻓﻘﺎ ﻟﻄﺮﻳﻘﺔ اﻟﺴﻤﻴﺔ ﻓﻲ آﻞ ﻣﻦ اﻟﻤﺠﻤﻮﻋﺎت اﻟﻤﺪروﺳﺔ وﻧﻮع اﻟﺴﻢ وم اﻟﺸﺎﺋﻌﺔ، ﻓﻲ اﻟﻤﺠﻤﻮﻋﺔ ١ ( اﻟﺤﺎﻻت اﻟﻌﺮﺿﻴﺔ ) ( ٤٣٫٨ ٪ )، ﺑﻴﻨﻤﺎ ﻓﻲ اﻟﻤﺠﻤﻮﻋﺔ ٢ ( ﺣﺎﻻت اﻻﻧﺘﺤﺎر ) آﺎن ( ٦١٫٩ ٪ ) ﺗﻨﺎول اﻷدوﻳﺔ .

وﻓﻘﺎ ﻟﻤﻮﻗﻊ اﻟﺘﻌﺮض ، ﻓﺈن ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت اﻟﺘﻲ ﺗﻌﺮﺿﺖ ﻟﻠﺴﻢ ﻓﻲ اﻟﻤﻨﺰل ( ٨٩٫٥ ٪ ) ، ﻓﻲ ﺣﻴﻦ أن اﻟﺤﺎﻻت اﻟﻤﺘﺒﻘﻴﺔ ﺗﺘﻌﺮض ﻟﻠﺴﻤﻮم ﺧﺎرج اﻟﻤﻨﺰل ( ١٠٫٥ ٪ ).

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻧﻮع اﻟﺴﻢ وﺗﻮاﻓﺮﻩ آﺒﻴﺮة ، وآﺎﻧﺖ اﻟﻤﺨﺪرات واﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ ﻋﻠﻰ ﻣﺴﺘﻮى ﻣﻨﺨﻔﺾ ، ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ أدوﻳﺔ اﻟﻮاﻟﺪﻳﻦ وﻣﻌﻈﻢ ﻣﺒﻴﺪات اﻵﻓﺎت ﻣﺘﻮﻓﺮة ﻓﻲ اﻟﻤﻨﺰل واﻟﻤﺮﺿﻰ ﻗﺎدرون ﻋﻠﻰ اﻟﻮﺻﻮل إﻟﻴﻬﺎ .

ﻣﻘﺎرﻧﺔ ﺑﻴﻦ ﻧﻮع وآﻤﻴﺔ اﻟﺴﻢ واﻟﻌﻼﻣﺎت اﻟﺤﻴﻮﻳﺔ آﺎن ذات د ﻻﻟﺔ إ ﺣﺼﺎﺋﻴﺔ ، وﺗﺄﺛﺮ ﻣﻌﻈﻢ ﺣﺎﻻت اﻟﺴﻤﻴﺔ ﻣﻊ اﻟﻤﺨﺪرات ﻋﻠﻰ اﻟﻌﻼﻣﺎت اﻟﺤﻴﻮﻳﺔ .

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻧﻮع وآﻤﻴﺔ ال ﺳﻢ و أﻋﺮاض اﻟﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي ﻣﻬﻤﺔ . ﺣﻴﺚ آﺎﻧﺖ ﻣﻌﻈﻢ ﺣﺎﻻت اﻟﺴﻤﻴﺔ ﻣﻊ اﻟﻤﺨﺪرات و ٥٠٪ ﻟﺪﻏﺔ ﺛﻌﺒﺎن.

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

ﺑﺎﻟﻨﺴﺒﺔ إﻟﻰ ﻧﻮع وآﻤﻴﺔ اﻟﺴﻢ وﻓﺘﺮة اﻟﻘﺒﻮل ﻟﻼﺳﺘﺸﻔﺎء ( اﻟﺤﺠﺰ ﺑﺎﻟﻤﺴﺘﺸﻔﻰ ) ، ﻓﻘﺪ أﻇﻬﺮت ﻋﻼﻗﺎت ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ وﻋﻼﻗﺔ ارﺗﺒﺎط ﻣﻮﺟﺒﺔ ﺑﻴﻦ ﻧﻮع وآﻤﻴﺔ اﻟﺴﻢ وﻓﺘﺮة اﻟﻘﺒﻮل .

آﺎﻧﺖ اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻧﻮع اﻟﺴﻢ واﻟﻨﺘﻴﺠﺔ ذات دﻻﻟﺔ إ ﺣﺼﺎﺋﻴﺔ، وﻣﻌﻈﻢ ﺣﺎﻻت اﻟﻤﺨﺪرات ، واﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ، واﻷدوﻳﺔ، وﻣﺒﻴﺪات اﻵﻓﺎت و ٥٠ ٪ ﻣﻦ ﻋﻀﺔ اﻟﺜﻌﺎﺑﻴﻦ ﺗﺤﺴﻨﺖ و ﺗﻢ ﺧﺮوﺟﻬﺎ .

وﻓﻘﺎ ﻟﻠﺤﺠﺰ ﺑﺎﻟﻤﺸﻔﻰ ﻓﻲ هﺬﻩ اﻟﺪراﺳﺔ ، ﻓﺈن ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت ﺗﻢ ﺣﺠﺰهﺎ ( ٧٨٫٣ ٪ )، ﻓﻲ ﺣﻴﻦ ﺗﻤﺜﻞ اﻟ ﺤﺎﻻت ﻟﻢ ﻳﺘﻢ ﺣﺠﺰهﺎ ( ٢١٫٧ ٪ ).

اﻟﻌﻼﻗﺔ ﺑﻴﻦ ﺳﺎﻋﺎت اﻟﺘﺄﺧﻴﺮ واﻟﺘﺨﻠﺺ ﻣﻦ اﻟﺴﻤﻮم، ﺗﻈﻬﺮ ﻋﻼﻗﺔ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ .

ﺑﺎﻟﻧﺳﺑﺔ ﻟﻟﻌﻼﻣﺎ ت ا ﻟﺣﻳ و ﻳﺔ، ﮐﺎﻧت ٦٨٪ ﻣ ن ا ﻟﺣﺎﻻت ذات ﻋﻼﻣﺎت ﺣﻳ و ﻳﺔ ﻃﺒﻴﻌﻴﺔ، ﺑﻳﻧﻣﺎ ﮐﺎﻧ ت ٣١٪ ﻣن ا ﻟﺣﺎﻻت ﻣﻊ ا ﻟﻌﻼﻣﺎ ت ا ﻟﺣﻳ و ﻳﺔ ا ﻟﻣﺗﺄﺛ رة وهﺒﻮط ﺣﺎد ﻓﻲ اﻟﻤﺆﺷﺮات اﻟﺤﻴﻮﻳﺔ٪ ١ .

ﺑﺎﻟﻨﺴﺒﺔ ل أﻋﺮاض اﻟﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي ، آﺎﻧﺖ ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﻓﻲ ﺣﺎﻟﺔ ﻃﺒﻴﻌﻴﺔ ( ٦٤٫٥ ٪ ) ﻳﻠﻴﻬﺎ اﻟﻨﻌﺎس ( ٣٠٫٣ ٪ ) واﻟﺘﺸﻨﺞ ( ٢ ٪ ) واﻟﻐﻴﺒﻮﺑﺔ اﻟﻌﻤﻴﻘﺔ ( ١٫٣ ٪ ).

ﮐﺎﻧ ت ا ﻟﻌﻼﻗﺎ ت ﺑﻳ ن ا ﻟﻌﻼﻣﺎ ت ا ﻟﺣﻳ و ﻳﺔ و أﻋﺮاض ﻣﺨﺘﻠﻔﺔ ﻟﻠﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي وا ﻟﻧﺗﺎﺋﺞ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ ، ﺣﻳ ث ﺗﺣﺳﻧ ت ﻣﻌ ﻇﻢ ا ﻟﺣﺎﻻ ت ذات ﻣﺆﺷﺮات ﺣﻴﻮﻳﺔ ط ﺑﻳﻌﻳﺔ و ﻣﺗﺄﺛ رة و ٥٠ ٪ ﻣ ن ا ﻟﺣﺎﻻ ت ذات هﺒﻮط ﻓﻲ اﻟﻮﻇﺎﺋﻒ اﻟﺤﻴﻮﻳﺔ و ﻗﺪ ﺗﻢ ﺧﺮوﺟﻬﺎ ﺑﻌﺪ اﻻﺳﺘﺸﻔﺎء ﺗﻤﺎﻣﺎ . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى ، ﻓﺈن ﻣﻌﻈﻢ اﻟﺤﺎﻻت ذات أﻋﺮاض ﻣﺨﺘﻠﻔﺔ ﻟﻠﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي ﻗﺪ ﺗﺤﺴﻨﺖ أﻳﻀﺎ وﻗﺪ ﺗﻢ ﺧﺮوﺟﻬﺎ ، اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﻌﻼﻣﺎت اﻟﺤﻴﻮﻳﺔ و أﻋﺮاض اﻟﺠﻬ ﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي وﻓﺘﺮة اﻟﻘﺒﻮل ﻟﻼﺳﺘﺸﻔﺎء ، آﺎﻧﺖ هﻨﺎك ﻋﻼﻗﺎت هﺎﻣﺔ ﺑﻴﻨﻬﻤﺎ . ﺣﻴﺚ ﺗﻢ ﻗﺒﻮل اﻟﺤﺎﻻت ذات اﻟﻌﻼﻣﺎت اﻟﺤﻴﻮﻳﺔ اﻟﻤﺘﺄﺛﺮة وﺣﺎﻻت اﻟﻐﻴﺒﻮﺑﺔ اﻟﻌﻤﻴﻘﺔ ﻷﻃﻮل ﻓﺘﺮة .

ﺑﺎﻟﻨﺴﺒﺔ ﻟﻟﻣﺳﺎﻋ دة ا ﻷ و ﻟﻳﺔ، ﻟم ﻳﺗ م إ ﺟ راؤهﺎ ﻓﻲ ٦٢٪ ﻣ ن ا ﻟﺣﺎﻻ ت، ﺑﻳﻧﻣﺎ ﻓﻲ ٣٥٪ ﻣ ن ا ﻟﺣﺎﻻت ﺗم إ ﺟ را ﺋﻬﺎ ﺑ ﻃﺮ ﻳﻘﺔ ﺧﺎ ط ﺋﺔ .

ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ﺑﻤﻌﺎﻟﺠﺔ اﻟﺤﺎﻻت ، ﺗﻨﺎول ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﻔﺤﻢ ﻓﻘﻂ ( ٥٠٫٧ ٪ )، ﻓﻲ ﺣﻴﻦ ﺧﻀﻊ ٢٧٪ ﻣﻦ اﻟﺤﺎﻻت ﻟﻐﺴﻞ اﻟﻤﻌﺪة وأﺧﺬ اﻟﻔﺤﻢ اﻟﻨﺸﻂ ، ٢٢٫٤ ٪ ﻣﻦ اﻟﺤﺎﻻت ﻟﻢ ﺗﺨﻀﻊ إﻟﻰ ﻣﻌﺎﻟﺠﺔ إزاﻟﺔ اﻟﺴﻤﻮم . آﺎﻧﺖ اﻟﺤﺎﻻت اﻟﺘﻲ ﺣﺼﻠﺖ ﻋﻠﻰ ﺗﺮﻳﺎق ﻣﺤﺪد ١٩٫٧ ٪ ﻣﻦ اﻟﺤﺎﻻت ، ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ اﻟﺤﺎﻻت اﻟﺘﻲ ﻻ ﻳﻮﺟﺪ ﻟﻬﺎ ﺗﺮﻳﺎق ﻣﺤﺪد ٥٥٫٣ ٪ . ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ﺑﺎﻟﻨﺘﻴﺠﺔ اﻟﻨﻬﺎﺋﻴﺔ ، ﻓﺈن ﻣﻌﻈﻢ اﻟﺤﺎﻻت ( ٥٢٫٦ ٪ ) ﻗﺪ ﺗﺤﺴﻨﺖ و ﺗﻢ ﺧﺮوﺟﻬﺎ ، ﻓﻲ ﺣﻴﻦ أن ٢١٫٧ ٪ ﺗﻢ ال ﺧﺮوج ﻋﻠﻰ ﻣﺴﺆوﻟﻴ ﺔ اﻟﻮاﻟﺪﻳﻦ، ٣٫٣ ٪ ﻣﻌﻘﺪ و ٠٫٧ ٪ ﻣﺎﺗﻮا .

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

آﺎﻧﺖ اﻟﻌﻼﻗﺎت ﺑﻴﻦ اﻟﻨﻮع و آﻤﻴﺔ اﻟﺴﻢ و درﺟﺔ ﺧﻄﻮرة اﻟﺴﻤﻮم آﺒﻴﺮة ، ﺣﻴﺚ آﺎﻧ ﺖ ﻏﺎﻟﺒﻴﺔ ﺣﺎﻻت اﻟﻤﻨﺘﺠﺎت اﻟﻤﻨﺰﻟﻴﺔ ( ٤٢٫٣ ٪ ) ، وﻣﺒﻴﺪات اﻵﻓﺎت ( ٥١٫٧ ٪ ) و ٥٠ ٪ ﻣﻦ ﻟﺪﻏﺎت اﻟﺜﻌﺎﺑﻴﻦ ﻣﻨﺨﻔﻀﺔ اﻟﺸﺪة ، ﻓﻲ ﺣﻴﻦ أن ﻏﺎﻟﺒﻴﺔ ﺣﺎﻻت اﻷدوﻳﺔ ( ٥٥٫١ ٪ ) و ٥٠ أﺧﺮى ﻣﻦ ﻟﺪﻏﺔ اﻟﺜﻌﺎﺑﻴﻦ آﺎﻧﺖ ﻣﻌﺘﺪﻟﺔ اﻟﺸﺪة . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى، ازدادت درﺟﺔ ﺧﻄﻮرة اﻟﺴﻤﻮم ﺑﻤﺠﺮد زﻳﺎدة ﺟﺮﻋﺔ اﻟﺴﻢ ، ﺣﻴﺚ أﻇ ﻬﺮت ﻣﻌﻈﻢ اﻟﺤﺎﻻت ذات اﻟﺠﺮﻋﺔ اﻟﻤﻨﺨﻔﻀﺔ ﺷﺪة ﻣﻨﺨﻔﻀﺔ، ﺑﻴﻨﻤﺎ أﻇﻬﺮت ﻣﻌﻈﻢ اﻟﺤﺎﻻت ﺑﺠﺮﻋﺔ أﻋﻠﻰ ﻣﻦ اﻟﺠﺮﻋﺔ اﻟﺴﻤﻴﺔ ﺷﺪة ﻣﻌﺘﺪﻟﺔ و ﻋﺎﻟﻴﺔ .

ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ﺑﺎﻟﻌﻼﻗﺔ ﺑﻴﻦ ﻧﻮع و آﻤﻴﺔ اﻟﺴﻢ واﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ اﻟﺤﺎدة واﻷﻣﺮاض اﻟﻤﺰﻣﻨﺔ ٢، آﺎﻧﺖ هﻨﺎك ﻋﻼﻗﺎت ﻣﻬﻤﺔ ﺑﻴﻨﻬﻤﺎ . ﺣﻴﺚ آﺎن اﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ اﻟﺤﺎدة واﻷﻣﺮاض اﻟﻤﺰﻣﻨﺔ ٢ ًﻋﺎﻟﻴًﺎ ﻓﻲ ﺣﺎﻻت ﺳﻤﻴﺔ اﻟﻤﺨﺪرات . أﻳﻀﺎ ، ﺗﻢ اﻟﻌﺜﻮر ﻋﻠﻰ اﻻرﺗﺒﺎﻃﺎت اﻹﻳﺠﺎﺑﻴﺔ ﺑﻴﻨﻬﻤﺎ . ﺣﻴﺚ آﺎن اﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ اﻟﺤﺎدة واﻷﻣﺮاض اﻟﻤﺰﻣﻨﺔ ٢ هﻮ اﻷﻗﻞ ﻓﻲ اﻟﺤﺎﻻت اﻟﺘﻲ أﺧﺬت أﻗﻞ ﻣﻦ اﻟﻜﻤﻴﺔ ا أهﻤﻴﺔ، ن اﻟﺴﻢ وزادت ﻣﻊ زﻳﺎدة آﻤﻴﺔ اﻟﺴﻢ .

اﻟﻌﻼﻗﺔ ﺑﻴﻦ اﻟﺘﺎرﻳﺦ اﻟﻤﺮﺿﻰ اﻟﺴﺎﺑﻖ ، ( ال ﻋﻼﻣﺎت ال ﺣﻴﻮﻳﺔ و أﻋﺮاض اﻟﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي )، وﻓﺘﺮة اﻟﻘﺒﻮل واﻟﻨﺘﻴﺠﺔ اﻟﻨﻬﺎﺋﻴﺔ واﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ اﻟﺤﺎدة واﻷﻣﺮاض اﻟﻤﺰﻣﻨﺔ ٢ آﺎﻧﺖ هﻨﺎك ﻋﻼﻗﺎت هﺎﻣﺔ ﺑﻴﻨﻬﻤﺎ وﻋﻼﻗﺎت إﻳﺠﺎﺑﻴﺔ .

آﺎﻧﺖ اﻟﻌﻼﻗﺎت ﺑﻴﻦ ( اﻟﻌﻼﻣﺎت اﻟﺤﻴﻮﻳﺔ و أﻋﺮاض اﻟﺠﻬﺎز اﻟﻌﺼﺒﻲ اﻟﻤﺮآﺰي ) و درﺟﺔ ﺧﻄﻮرة اﻟﺴﻤ ﻮم ذات أهﻤﻴﺔ ، ﺣﻴﺚ أﻇﻬﺮت ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت ذات درﺟﺔ وﻋﻰ ﻃﺒﻴﻌﻴﺔ ﺷﺪة ﻣﻨﺨﻔﻀﺔ وآﺎﻧﺖ ﺟﻤﻴﻊ ﺣﺎﻻت اﻟﻐﻴﺒﻮﺑﺔ اﻟﻌﻤﻴﻘﺔ ﺷﺪﻳﺪة اﻟﺨﻄﻮرة . ﻣﻦ ﻧﺎﺣﻴﺔ أﺧﺮى، أﻇﻬﺮ اﻟﻤﺮﺿﻰ اﻟﺬﻳﻦ ﻳﻌﺎﻧﻮن ﻣﻦ ﻋﻼﻣﺎت ﺣﻴﻮﻳﺔ ﻃﺒﻴﻌﻴﺔ ﺷﺪة ﻣﻨﺨﻔﻀﺔ، وﺣﺎﻻت هﺒﻮط اﻟﻮﻇﺎﺋﻒ اﻟﺤﻴﻮﻳﺔ أﻇﻬﺮت ﺷﺪة ﻋﺎﻟﻴﺔ .

ﻓﻴﻤﺎ ﻳﺘﻌﻠﻖ ب اﻟﻌﻼ ﻗﺔ ﺑﻴﻦ اﻟﻨﺘﺎﺋﺞ و درﺟﺔ ﺧﻄﻮرة اﻟﺴﻤﻮم آﺎﻧﺖ ذات دﻻﻟﺔ إﺣﺼﺎﺋﻴﺔ، ﺗﻢ ﺗﺤﺴﻦ ﻏﺎﻟﺒﻴﺔ اﻟﺤﺎﻻت اﻟﺘﻲ أﻇﻬﺮت ﺷﺪة ﻣﻨﺨﻔﻀﺔ وﺷﺪة ﻣﻌﺘﺪﻟﺔ وﺧﺮوﺟﻬﺎ ، ﻓﻲ ﺣﻴﻦ آﺎﻧﺖ ﻣﻌﻈﻢ اﻟﺤﺎﻻت اﻟﻤﻌﻘﺪة ذات ﺷﺪة ﻋﺎﻟﻴﺔ .

ﺑﻌﺾ اﻟﺘﻮﺻﻴﺎت ﻟﻠﺤﺪ ﻣﻦ ﺣﺎﻻت اﻟﺘﺴﻤﻢ ﺑﻴﻦ اﻷﻃﻔﺎل:

اﻻﺣﺘﻔﺎظ ﺑﺎﻷدوﻳﺔ واﻟﻤﻮاد اﻟﺴﺎﻣﺔ ﺑﻌﻴﺪ ا ﻋﻦ ﻣﺘﻨﺎول اﻷﻃﻔﺎل، ﻋﺪم ﺗﻨﺎول اﻷدوﻳﺔ أﻣﺎم اﻷﻃﻔﺎل، ﻋﺪم ﺗﺸﺒﻴﻪ اﻟﺪواء ﻟﻬﻢ ﺑﺎﻟﺤﻠﻮى آﻲ ﻳﺘﻨﺎوﻟﻪ. ﻋﻤﻞ دورات ﺗﺪرﻳﺒﻴﺔ ﻟﻶﺑﺎء واﻷﻣﻬﺎت ﻓﻲ اﻟﻤﺴﺎﻋﺪات اﻷوﻟﻴﺔ، وﺗﺄهﻴﻠﻬﻢ ﻟﻠﺘﻌﺎﻣﻞ ﻣﻊ أوﻻدهﻢ ﻓﻲ اﻟﻤﺮاﺣﻞ اﻟﻌﻤﺮﻳﺔ اﻟﻤﺨﺘﻠﻔﺔ و ﺧﺎﺻﺔ اﻟﻤﺮاهﻘﺔ. رﻓﻊ ﻣﺴﺘﻮى اﻟﺘﻌﻠﻴﻤﻲ و اﻟﺜﻘﺎﻓﻲ ﻟﻠﻮاﻟﺪ ﻳﻦ، ورﻓﻊ اﻟﻮﻋ ﻲ ﻟﺪﻳﻬﻢ ﺑﺴﺮﻋﺔ اﻟﺘﻮﺟﻪ ﻟﻠﻤﺮاآﺰ اﻟﺘﺨﺼﺼﻴ ﺔ ﻓﻲ ﺣﺎل ﺗﻌﺮض اﻷﻃﻔﺎل ﻟﻠﺘﺴﻤﻢ أو اﻻﺷﺘﺒﺎﻩ ﻓﻲ ذﻟﻚ.

اﻟﻤﻠﺨﺺ اﻟﻌﺮﺑﻲ

اﻻهﺘﻤﺎم ﺑﻨﻔﺴﻴﺔ اﻷﻃﻔﺎل وﺧﺎﺻﺔ اﻹﻧﺎث و اﻻﻋﺘﻨﺎء ﺑﻬﻦ . ﺗﺠﻨﺐ اﻟﻤﺸﺎآﻞ أﻣﺎم اﻷﻃﻔﺎل وﻋﺪم ﺟﻌﻞ اﻷﻃﻔﺎل ﺟﺰء ﻣﻨﻬﺎ . اﻻهﺘﻤﺎم ﺑﺎﻟﻤﺮأة اﻟﻌﺎﻣﻠﺔ واﻟﺴﻤﺎح ﻟﻬﺎ ﺑﺎﻻﻧﺘﺒﺎﻩ ﻷﻃﻔﺎ ﻟﻬﺎ. ﻋﻤﻞ دورات ﺗﺪرﻳﺒﻴﺔ ﻟﻸﻃﺒﺎء اﻟﺠﺪد ﻓﻲ آﻴﻔﻴﺔ اﻟﺘﻌﺎﻣﻞ ﻣﻊ ﺣﺎﻻت ﺗﺴﻤﻢ اﻷﻃﻔﺎل، زﻳﺎدة اﻟﻮﻋﻲ ﻟﺪى اﻷﻃﺒﺎء ﻋﻦ ﺧﻄﻮرة اﻟﺴﻤﻮم اﻟﺘﻲ ﺗﺆﺛﺮ ﻋﻠﻰ اﻟﻤﺆﺷﺮات اﻟﺤﻴﻮﻳﺔ و درﺟﺔ اﻟﻮﻋﻲ ﻟﺪى اﻷﻃﻔﺎل.

ﺣﺎﻻت ﺗﺴﻤﻢ اﻷﻃﻔﺎل اﻟﻤﺘﻌﻤﺪ ﻓﻲ ﻣﻘﺎﺑﻞ ﺣﺎﻻت ﺗﺴﻤﻢ اﻷﻃﻔﺎل اﻟﻐﻴﺮ ﻣﺘﻌﻤﺪ ﺑﺎﻟﻤﺮآﺰ اﻟﻘﻮﻣﻲ ﻷﺑﺤﺎث اﻟﺴﻤﻮم اﻟﺒﻴﺌﻴﺔ واﻹآﻠﻴﻨﻴﻜﻴﺔ

رﺳﺎﻟﺔ ﻣﻘﺪﻣﺔ ﻣﻦ اﻟﻄﺒﻴﺒﺔ/ راﻧﻴﺎ ﻣﺤﺴﻦ ﻋﺒﺪ اﻟﺮﺣﻴﻢ إﺑﺮاهﻴﻢ ﺑﻜﺎﻟﻮرﻳﻮس اﻟﻄﺐ واﻟﺠﺮاﺣﺔ ﻣﻌﻴﺪ ﺑﻘﺴﻢ اﻟﻄﺐ اﻟﺸﺮﻋﻲ واﻟﺴﻤﻮم اﻹآﻠﻴﻨﻴﻜﻴﺔ آﻠﻴﺔ ﻃﺐ ﻗﺼﺮ اﻟﻌﻴﻨﻲ

ﺗﻮﻃﺌﺔ ﻟﻠﺤﺼﻮل ﻋﻠﻰ درﺟﺔ اﻟﻤﺎﺟﺴﺘﻴﺮ

ﻓﻲ

اﻟﻄﺐ اﻟﺸﺮﻋﻲ واﻟﺴﻤﻮم اﻹآﻠﻴﻨﻴﻜﻴﺔ

ﺗﺤﺖ إﺷﺮاف

أ.د. دﻳﻨﺎ ﻋﻠـﻲ ﺷﻜﺮي أﺳﺘﺎذ ورﺋﻴﺲ ﻗﺴﻢ اﻟﻄﺐ اﻟﺸﺮﻋﻲ واﻟﺴﻤﻮم اﻹآﻠﻴﻨﻴﻜﻴﺔ آﻠﻴﺔ ﻃﺐ ﻗﺼﺮ اﻟﻌﻴﻨﻲ

أ.د. هﺪى ﻋﺒﺪ اﻟﻤﺠﻴﺪ اﻟﻐﻤﺮي أﺳﺘﺎذ اﻟﻄﺐ اﻟﺸﺮﻋﻲ واﻟﺴﻤﻮم اﻹآﻠﻴﻨﻴﻜﻴﺔ آﻠﻴﺔ ﻃﺐ ﻗﺼﺮ اﻟﻌﻴﻨﻲ

د. ﻣﺮوة اﺳﺤﻖ ﻣﺤﻤﺪ ﻣﺪرس اﻟﻄﺐ اﻟﺸﺮﻋﻲ واﻟﺴﻤﻮم اﻹآﻠﻴﻨﻴﻜﻴﺔ آﻠﻴﺔ ﻃﺐ ﻗﺼﺮ اﻟﻌﻴﻨﻲ

آﻠﻴﺔ اﻟﻄﺐ ﺟﺎﻣﻌﺔ اﻟﻘﺎهﺮة ٢٠١٨