Primary Care RAP August 2018 Written Summary

Editor-in-Chief: Neda Frayha MD ​ Associate Editor: Kenji Taylor MD, MSc ​

Intro - Good Samaritan Laws Brandon Grove MD, Neda Frayha MD

Pearls: ● Good Samaritan Laws provide guidance on medical liability for medical and non-medical providers who offer care as bystanders or “samaritans”. They vary by state and country but generally protect medical providers from medical liability assuming the provider is practicing within their scope.

● Good Samaritan Laws: ○ General laws that deal with medical liability and obligation to provide care in the case of a medical provider as a bystander (ie: airplane, baseball field, walking down the street) ○ Differ by state, country and even airline ■ US, Canada and Britain are similar ■ France, Germany and other countries actually obligate aid and if not offered may result in fines or imprisonment ■ States vary: some protect medical providers from legal suits while others protect all samaritans ○ US law does not obligate us to act while our ethical duty would suggest we do ■ The Aviation Medical Assistance Act of 1998 was put into place to: ● 1. Protect the airline and “samaritan” if: ○ The samaritan is medically qualified (ie: a psychiatrist treating an MI may or may not be covered) ○ The samaritan needs to act voluntarily ○ The samaritan acts in good faith ○ The samaritan does not engage in gross negligence or willful misconduct ○ The samaritan does not receive compensation, though travel vouchers and upgrades do not count ● 2. Required standardization of medical supplies on an airplane ○ General tips before providing medical care as a samaritan: ​

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■ 1. Assess your own state of mind. If you’ve had something to drink or an ativan before getting on a plane, you may not be able to provide care. ■ 2. If possible, obtain verbal consent from the person ■ 3. Use an interpreter if available ■ 4. Utilize ground-based medical services as they are often available ■ 5. If you think diversion is medically indicated, it is your call to make. ■ 6. Document what happened ■ 7. Don’t practice outside your scope of medicine

Interstitial Lung Disease Made Simple Nirav Shah MD, Neda Frayha MD

Pearls: ● Interstitial lung diseases are a large and diverse group of ailments that can be divided into four main groups: smoking-related, steroid-responsive, connective tissue-related and exposure-related. ● Diagnosis includes pulmonary function tests and high resolution CT. ● Treatment is dependent on the type. Do not start steroids until you know what you’re dealing with because it may cause further complications and muddy the diagnostic window.

● Interstitial Lung Disease (aka: diffuse parenchymal lung disease): diverse and large group ​ of lung diseases (more than 140 different ones) that can be thought of as follows: ○ 1. Smoking-related ○ 2. Steroid-responsive ○ 3. Connective tissue-related ○ 4. Exposure-related ● Clinical presentation concerning for ILD ○ Shortness of breath or dyspnea: may initially be with exertion and then progress to be even at rest. ○ Cough ○ Headache given chronic hypoxia ○ Back tightness and back pain ○ Crackles on lung exam (velcro-like or dry crackles) ○ Non-acute, insidious process ● Smoking-related ILD: ​ ○ Types: ■ Desquamative interstitial (DIP) ■ Respiratory interstitial lung disease (RBILD) ■ Pulmonary Langerhans cell histiocytosis (PLCH)

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■ Idiopathic (IPF): whole upcoming episode on this diseases ○ Thought of as a continuum of diseases in all people who smoke but not all progress to interstitial lung disease ○ Counseling: STOP SMOKING. Definitive treatment for PLCH is smoking cessation. ● Steroid-responsive ILD: ○ Types: ■ ● Thought to be genetic predisposition plus environmental trigger but exact cause is unknown ● 6-9 months of early prednisone taper results in symptoms improvement and resolution of abnormalities found on imaging ■ Organizing pneumonia - if no cause is found it is called cryptogenic organizing pneumonia ● Lung heals itself from the outside in, so you get peripheral sparing on CT scan ● Pearl: Often these patients have presented with , cough and ​ consolidation on imaging. They are treated with and their symptoms don’t resolve. They then have a biopsy or further imaging for diagnosis and treatment with steroids. ■ ● Steroids dampen the eosinophilic response ■ Hypersensitivity pneumonia ● Needs to remove the trigger and treat with steroids ● Connective tissue-related: ○ Types: ■ Rheumatoid arthritis: often times presents with RA symptoms first or the lung disease is caught first while on hindsight they had typical RA symptoms all along ■ Lupus ■ Scleroderma ■ Polymyositis ■ Dermatomyositis ○ Treatment: if you treat the underlying connective tissue disease you also treat the lung disease; hence, serologies to identify the underlying disease is really important. ■ Often times steroid-sparing agents like methotrexate ● Exposure-related: ​ ○ Types: ■ Asbestos: huge latency between exposure and disease onset ■ Amiodarone ■ Coal ■ Silica

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■ Beryllium ○ Treatment: remove the exposure and protect against future exposure ● Focus of history: ​ ○ Characterize dyspnea severity (flight of stairs, walk to mailbox), duration and compensation ○ Characterize cough ■ Sputum color ■ Chronic ■ Worse at night, humid or dry settings, laying flat, taking a shower ● Physical exam: ○ General breathing pattern at rest and with conversation ○ Ambulatory oxygenation ○ Thorough skin exam ○ Lung and cardiac exam ● Work-up: ○ Full set of pulmonary function tests looking for restrictive lung pattern → ​ ​ ■ Decreased forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and decrease in total lung capacity (TLC). Normal or even elevated ratio of FEV1 to FVC. ■ May also see decrease in diffusion lung capacity (DLCO) ○ Often will order inspiratory and expiratory mouth pressures because it tells whether or not they are having any weakness associated with the ILD ○ High resolution CT scan ○ May also do inspiratory/expiratory or prone/supine films to see how much air trapping there is ● Treatment: ○ If hypoxic, give them oxygen for at rest or with exertion ○ Don’t start steroids unless you know you have a steroid-responsive interstitial lung disease ○ Referral to pulmonology ○ Health maintenance: flu and pneumonia vaccine

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Post Syncope ECG Red Flags Malcolm Thaler MD, Matthew Delaney MD

Pearls: ● The ECG is a simple and cost effective tool to use in the evaluation of syncope. ● The red flags patterns (and details below) to look for in an ECG are: ○ 1. Hypertrophic cardiomyopathy ○ 2. Long QT syndrome ○ 3. Wolff-Parkinson-White ○ 4. Brugada’s ○ 5. Arrhythmogenic right ventricular cardiomyopathy

● Clinical Case: 35 year-old healthy male training for a half marathon, runs three times per ​ week. When he’s running halfway through his 4 or 5 miles, he feels like he is going to pass out. This has happened twice and a third time he actually passed out while running. Physical exam is normal. ECG is normal. What else about the ECG should really get us concerned? ● ECG red flags in syncopal-related events: ​ ○ 1. Hypertrophic cardiomyopathy ○ 2. Long QT syndrome ○ 3. Wolff-Parkinson-White ○ 4. Brugada’s ○ 5. Arrhythmogenic right ventricular cardiomyopathy ● 1. Hypertrophic cardiomyopathy: hypertrophy of the left ventricle and particularly the ​ left ventricular septum that leads to obstruction of the outflow tract, impaired ventricular filling which is a set up for arrhythmias that generate themselves and cause problems. ○ Common - the leading cause of sudden cardiac death in young people ○ Autosomal dominant with high penetrance ○ Caused by disorganized muscle fibers that leads to hypertrophy ○ Diagnostic criteria on ECG: ​ ■ Left ventricular hypertrophy ■ Sharp, narrow and deep Q waves in the lateral and inferior leads ○ Treatment: ​ ■ Beta blockers and calcium channel blockers to reduce the excitability of the heart muscle and reduce contraction ■ If the patient has come in with a prior episode of syncope or sudden cardiac death from which they were resuscitated, you’ll want to put in an implantable cardiac defibrillator ○ Pearl: ​ ■ Get a good family history because a history of other families with syncope or sudden cardiac death may support the diagnosis. You may also consider screening other family members with serial ECGs and echos

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■ The hypertrophy and disease can evolve over time so screening family members every couple of years is a good idea ■ Ask about drowning: there is thought to be an association between drowning and several congenital arrhythmias ● 2. Long QT syndrome (congenital): ​ ○ Definition: ■ Men - 0.45 seconds ■ Women - 0.47 seconds ■ Pearl: cardiologist don’t worry about it until >0.5 seconds. Also, 10% of ​ patients with long QT syndrome will have a normal QT on resting ECG. ○ Many causes: ■ Drugs: antiarrhythmics, macrolides, quinolone antibiotics, non-sedating ​ antihistamines, antifungal drugs, psychotropics, tricyclics, SSRIs) that can lead to a lethal torsades de pointes. ■ Electrolytes: low K, low Ca, low Mg ​ ■ Congenital: common in both men and women ​ ○ Management of congenital: ■ Treated with beta blockers and occasionally implantable cardiac defibrillators ■ Avoidance of competitive sports to avoid adrenaline surges; however, modest exercise is ok ■ Counseling family members since it is inherited ○ Short QT syndrome: ■ Also congenital with increased risk of both atrial and ventricular arrhythmias ■ Also acquired forms from hyperkalemia and hypercalcemia ● 3. Wolff-Parkinson-White ○ Accessory pathway connects the atria and ventricles, bypassing the AV node and delivering the current more quickly into the ventricles ■ The pathway may be between right atria to right ventricle, left atria to left ventricle or even within the AV node itself, which would not generate a delta wave ○ Short PR (<0.12 seconds) and early uptick of the QRS complex (delta wave) that represents early depolarization of part of the ventricles ○ At risk for both atrial and ventricular arrhythmias ■ You may classically see someone with atrial fibrillation with a rate of about 300 because the AV node cannot block the conduction from the atria to ventricles ■ You may also see AV reciprocating ventricular tachycardia that may look like ventricular tachycardia. Treat it as though its ventricular tachycardia because you’re not going to do any harm and it is more lethal. ○ Fortunately, the first episode is usually not fatal and the accessory pathway is easily identified and ablated

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● 4. Brugada’s ○ Autosomal dominant with variable expression affecting the sodium channels leading to disrupted repolarization and fatal arrhythmias ○ Fatal sudden death arrhythmias are more common when patient is either sleeping or has a fever ○ ECG findings: ■ Right bundle branch pattern - rabbit ears in V1 and V2 ■ ST elevation in V1 through V3 ■ Flipped T waves in V1 and V2 ○ Screen family members ○ Get to cardiologist more urgently as this is more likely to lead to fatal arrhythmias ● 5. Arrhythmogenic right ventricular cardiomyopathy ○ Genetic condition leading to fatty deposits in the right and left ventricle and mutation in the way cells adhere as well as communicate with each other ○ ECG finding: ■ Epsilon wave - tiny positive deflection in the QRS complex ​

Source: ECGpedia.org ■ T wave inversions in V1 and V3 ○ Screen family members ○ Refer to cardiology ○ Restrict competitive activities ○ Beta blockers have been shown to decrease the risk of arrhythmias

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Weight Gain in Middle Age: The Problems and The Solutions Ava Port MD, Neda Frayha MD

Pearls: ● Weight gain in middle age can be explained in part in women by a decrease in estradiol and rise in FSH that leads to changes in body fat distribution, decrease in lean body mass and decrease in overall metabolic rate. ● When evaluating a patient, remember to look over their meds as common ones like steroids, beta-blockers, antidepressants, antipsychotics and diabetes meds can cause weight gain. ● On a physical exam, be on the lookout for pathology such as Cushing’s disease or hyperandrogenism that may have an underlying cause. ● Checking FSH and estradiol levels is not helpful and won’t change management. Consider a TSH. ● Remember your toolbox for addressing weight gain: caloric deficit through meal planning and activity monitoring, medications and surgery.

● Reader question: Hippo Education, I was wondering if you ever take requests on topics. I am really struggling with this one. Women in their 40's with weight gain. They always think it's from some hormone imbalance. Is that possible? Should I be checking the FSH or estradiol or LH? I want to just tell them it's diet and exercise, but they don't believe me. I would love to hear your thoughts." ● What happens to the physiology in 40’s or perimenopause, 10 years prior to onset of menopause? ○ As ovarian follicles start dropping off, patients age, fertility declines → estradiol levels decrease and FSH levels rise leading to the following changes: ■ Body fat distribution to a more central visceral fat depot versus fat collecting at the hip and thigh area → increased risk for metabolic disease ■ Decrease in lean body mass ■ Decrease in overall metabolic rate: need about 200 calories less per day ● What is your approach to these patients? ○ Determine a baseline: have they always struggles with weight or is this weight gain relatively rapid ○ Med reconciliation for those that can cause weight gain: ■ Steroids ■ Beta-blockers ■ Antipsychotics ■ Antidepressants ■ Diabetes meds ○ Stressors that have led to lifestyle changes (ie: surgery, depression, job changes) ○ History of eating disorders ○ Sleep problems ○ Diet factors

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■ How often do you eat? ■ When do you eat? ■ Are you eating close to bedtime? ■ Who’s cooking and doing the shopping? ■ Sugar beverage intake? ○ Activity habits: when somebody is starting a weight loss program, you may recommend against strenuous burst exercise because it drives your hunger to compensate. Instead, gradually increase lower impact cardio and once you get to a point of weight maintenance, ramp it up to build more lean mass to help keep your metabolic rate a little higher. ● Physical exam? ○ Acanthosis nigricans, darkening around the nape of the , groin folds and armpits is a sign of insulin resistance. ○ Skin tags are more prevalent but not necessarily pathologic in obese individuals. ○ Signs of Cushing’s disease: ​ ■ Lipodystrophy with fat around the trunk and neck are despite very lean limbs ■ Striae - thick, purple or pinkish because the skin is stretched so thin ■ Dorsocervical fat pad or buffalo hump (firm fat pocket not be confused with a more generalized adiposity in people who are morbidly obese) ○ Acne and hirsutism may be a sign of hyperandrogenism associated with PCOS or a virilizing tumor ● Work-up? ○ Checking FSH and estradiol levels are not super helpful because they have to be taken in context of the menstrual cycle. ○ Also confirming a patient is perimenopausal with an estrogen level isn’t going to change your management of a weight loss program. ○ Many patients may want their thyroid checked and the prevalence is higher in women in their 40’s to 50’s → check a TSH but interpret carefully! ● Weight loss: ○ 1. Start by setting a calorie goal to promote weight loss by creating a calorie deficit. ■ If female patient less than 250 pounds, typically calorie goal of 1200-1500 calories ■ If female patient over 250 pounds, typically goal of 1500-1800 calories ● Roughly 10-15 kilocalories per kilogram of weight per day ■ Given them a reasonable goal based on historically how they have weighed when they were younger to set them up for successes early on. ○ 2. Meal planning advice: ■ Try to minimize each meal itself by eating no more than 500 calories at once ■ If looking at carb content, try not to have more than 30g per day (can of soda, two slices of bread, medium banana, 8 cups of bell pepper). The average American consumes 350g per day

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■ High quality calories are important. Get away from fried foods and animal fats ■ High fiber foods are slower to digest and will cause your blood sugar to spike less ○ 3. Medications (check out November 2015 episode of Primary Care RAP for more detail): ■ Estrogen replacement therapy has not been helpful in managing people’s weight. It may attenuate weight gain in premenopausal women but certainly not after menopause. ■ When to start thinking about medications? ● BMI of or greater than 27 and comorbidity (diabetes, arthritis, PCOS) or a BMI of or greater than 30 without comorbidity ● May help motivate people in early stages to reinforce healthy habits ■ Potential for weight regain at about 6 to 12 months so really great for use in highly motivated people ■ GLP-1 agonists: ​ ● Great for use in diabetics trying to lose weight ● Approved for long-term use ● Few side effects (rarely pancreatitis or hypoglycemia unless used in combination with secretagogues) ● Suppress appetite and gastric emptying ● Also can be used in non-diabetics in the form of liraglutide (injectable) ■ Stimulants (ie: phentermine): ● Appetite stimulants ● Not FDA-approved for long-term use because tendency to build up tolerance in 3 to 6 months ● Intermittent use (every other day) has demonstrated good success rates from studies in the 1980’s ■ Appetite and behavioral-modulating: ​ ● Contrave© (buproprion and naltrexone) ○ Works well with people who are bingers or cravers to try to interrupt the reward pathway ● Lorcaserin - targets serotonin pathways in the brain ○ May work well with mood-related eating ● Only about ⅓ of payers cover appetite suppressants → otherwise they are expensive ○ 4. Surgery: ■ Criteria: BMI > 35 with comorbidity or >40 with no comorbidity. ● Lower cutoffs in some Asian populations ● BMI > 40 is where there is definitely benefit over medications

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Diaper Rash Mizuho Spangler DO, Matthieu DeClerck MD & Brittney DeClerck MD

Pearls: ❏ Use ointments instead of creams in the treatment of diaper rash. The first line treatment for mild cases is a topical zinc paste ❏ Use a hair dryer on low heat to remove any moisture between diaper changes

BACKGROUND ● Diaper rash is an irritant contact dermatitis caused by the combination of urine and feces together. ● The breakdown of skin and a moist environment can lead to secondary with the most common being candida, staph and strep.

DIFFERENTIAL DIAGNOSIS ● Patients with diaper rash that is refractory to standard medical management may have an allergic contact dermatitis to the baby wipes or the diaper. ● Eczema, atopic dermatitis and severe seborrheic dermatitis can involve the diaper area mimicking diaper rash. ● Inverse psoriasis which appears on the groin, perianal area, breasts and axilla instead of the extensor surfaces, can also look like diaper rash. ● Langerhans cell histiocytosis is a hematologic malignancy that will appear similar to a severe case of seborrheic dermatitis on the groin. The rash will be erythematous, with a yellow-brown hue with petechiae. ● Zinc deficiency, in areas where malnutrition is common, can cause a rash on the groin and buttocks. ● Jacquet's erosive dermatitis is a severe form of diaper rash that has characteristic punched out erosions.

MANAGEMENT ● If the baby already has a painful macerated diaper rash, consider rinsing the baby’s buttocks with lukewarm water instead of using wipes that have irritating preservatives ● Ointment is the preferred topical medium of choice, rather than creams, in the treatment of diaper rash. ● For all patients with diaper rash good hygiene including frequent diaper changes, effective drying and diaper-free time are critical interventions ● Dry the baby’s bottom with a dryer on a low heat setting to maximize moisture removal between diaper changes. ● For mild forms of diaper rash use a topical zinc paste in lower concentrations (12% or 13%). Apply the zinc paste diligently to get maximum effect ● For moderate to severe diaper rash:

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○ First apply a nystatin and mupirocin ointment. ○ Second, apply a layer of zinc paste over the ointment. Higher percentages of zinc can be used for more intense rashes. ○ A 1% hydrocortisone ointment can also be applied, in the minimal amount necessary, to reduce inflammation.

Mononucleosis Matt Delaney, MD and Sol Behar, MD

Pearls: ❏ Typical symptoms of Epstein Barr virus (EBV) are , , and in a teenager ❏ When testing for EBV, Monospot is good in older kids, especially after illness has been around >5-7 days. Younger kids don’t make heterophile Ab as often so you should send EBV titers in this population to make the diagnosis ❏ Rash after administration is a common side effect in kids with EBV infection, especially if it is ampicillin, less so with PCN’s. It is NOT an allergic reaction

● Mononucleosis is caused by Epstein Barr virus ● Peak age of incidence is 10-19 years. ● Symptoms include: ○ ○ lymphadenopathy (posterior) ○ palatal petechiae ○ tonsillar swelling ○ sometimes splenomegaly (which we are not great at detecting) ○ younger kids may have Fever of Unknown Origin as only presenting symptom ● EBV is spread through saliva and has a long incubation period (weeks) ● EBV infection must be differentiated from strep throat, as there are many overlapping symptoms. Patients can test (+) for both- the question becomes: are you colonized with strep or is it a true infection? ○ Adults have ~30% rate of colonization with strep, while younger children have a lower incidence of ~10% ○ If fevers persist for more than 48 hrs while on antibiotics in child (+) for both EBV and strep, this probably reflects the body responding to EBV ○ ● Testing: ○ Monospot- tests for presence of Heterophile antibody. It is a good test in older kids, esp after illness has been present for at least 5-7 days . ○ Younger kids don’t make heterophile antibody as often as older ones. Use EBV titers to make the diagnosis in this age group. EBV VCA IgM is elevated in kids with recent new EBV infection.

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○ EBV PCR is a very sensitive test, but values are not standardized. Therefore it is mostly used in research settings or for screening purposes in those with rare malignancies, or in children s/p transplant . ○ CBC: shows atypical lymphocytosis, low/normal platelets counts. ○ LDH and transaminases (AST/ALT) can be elevated.

● Complications: ○ Splenomegaly and rupture is a rare (0.05-0.1%) but a concern for ​ those in contact sports ■ Keep out of sports for 3 weeks-1 month ■ Can present with left sided abdominal pain or life-threatening hemorrhagic shock ■ Delaney uses to determine absence or presence of splenomegaly in a child who wants to return to sports in less than 1 month ○ Rash after antibiotic administration is a common side effect, esp if it is ampicillin (95-100% incidence), less so with PCN’s (~50%)- NOT an allergy! ○ Airways obstruction (the most common cause of pediatric hospitalization in EBV). ○ Rarely, aseptic meningitis or autoimmune hemolytic anemia can occur. ○ EBV plays a role in development of lymphoproliferative disorder in immunosuppressed children or kids with transplants. ● Treatments: ○ Steroids may help with short term pain at 12 hours, some clinicians will use it in ​ setting of upper . ○ There is no evidence to support longer courses of steroids in EBV infection. ○ Antivirals play no role in the otherwise healthy patient with EBV infection. ​ ​ ​

New Stroke Guidelines Andrew Buelt DO

Pearls: ● The DAWN and DEFUSE trials demonstrated patients with acute ischemic stroke who were randomized to endovascular intervention and met very specific criteria had both significant functional and survival benefits at 90 days. ● These two trials have changed stroke guidelines. Review below and let us know how this will change your practice at Primary Care RAP online!

● Updated stroke guidelines: ○ Patients should be considered for thrombectomy in under six hours after stroke onset if they meet the following criteria: ■ Pre-stroke modified Rankin Scale Score of 0 to 1

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■ Causative occlusion of the internal carotid artery or middle cerebral artery segment ■ Age of 18 ■ National Institutes of Health Stroke Scale Score of six or greater ■ Alberta Stroke Program Early CT Score of six or greater ○ Patients eligible for IV alteplase should receive IV alteplase even if thrombectomy is being considered ○ Patients undergoing consideration from mechanical thrombectomy, observation after IV alteplase to assess for clinical response should not be performed ○ Recommend thrombectomy in eligible patients 6 to 16 hours after a stroke (level 1A) ○ Reasonable for patients to undergo mechanical thrombectomy from 16 to 24 hours after stroke (level 2A) ● Trials supporting the latest guidelines: ○ DAWN Trial: ■ Background: ● The NIH stroke scale (NIHSS) scores patients from 0 to 4 on level of ​ ​ consciousness, orientation, command following, gaze, visual fields, facial palsy, ataxia using nose and heel to shin, description of a picture and extinction. Normal is zero. A score of 6 is abnormal. ■ Method: multi-center prospective randomized open label trial that enrolled 206 patients with stroke meeting specific criteria randomized to thrombectomy + standard care or just standard care alone. ● Primary endpoints: ○ Mean score for disability on Utility-Weighted Modified Rankin Scale which ranges from 0 (death) to 10 (no symptoms or no disability at all) ○ Rate of functional independence at 90 days ● Inclusion criteria: ○ Age over 18 ○ NIHSS scale greater than 10 ○ Randomized between 6 and 24 hours of last well known ○ No significant prestroke disability ○ Anticipated to live longer than 6 months ○ Able to attend follow up visits ○ Less than one third of the middle cerebral artery territory involved as evidenced by CT or MRI ○ Occlusion of the intracranial internal carotid artery, and/or the middle cerebral artery as evidenced by MRA ○ Clinical imaging mismatch defined by MRI diffuse weighted imaging or CT perfusion ■ Perfusion software algorithms determine salvageable brain tissue

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● Results: ○ Mean time of last known well was 13.6 hours ○ Functional independence at 90 days in thrombectomy arm was 49% vs. standard arm 13%. ○ No difference in stroke related death at 90 days in symptomatic intracranial hemorrhage ● Limitation: stopped early because intervention was better and therefore limited power of some of the analysis ● Conclusion: In patients with acute anterior ischemic stroke last known to be normal or well 6 to 24 hours and had a perfusion mismatch on imaging thrombectomy appeared to improve their functional independence at 90 days. ■ Nogueira RG et. al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. PMID: ​ 29129157. ​ ■ ○ DEFUSE: ■ Method: multi-center randomized open label trial with blinded outcome assessment looking at thrombectomy + medical therapy vs. medical therapy alone in 180 patients 6 to 16 hours after stroke symptoms with some ischemic brain tissue. ● Primary endpoints: ○ Modified Rankin Score at 90 days ● Inclusion criteria: ○ Age 18-90 ○ NIHSS greater than 6 ○ Ability to undergo endovascular therapy between 6 to 16 hours from when you were last normal ○ Occlusion of a cervical or intracranial internal carotid artery or proximal middle cerebral artery on CTA or MRA ○ Initial infarct size of less than 70 ml or a ratio of volume of ischemic tissue on perfusion imaging to infarct volume of greater than 1.8 ● Results: ○ Mean time of last known well was 10.5 hours ○ Functional independence at 90 days in thrombectomy arm was 45% vs. standard arm 17% ○ Mortality in endovascular group was 13% and in medical only group was 23% ○ No significant difference in serious adverse events ● Limitation: stopped early because endovascular intervention superior

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● Conclusion: In patients with acute large vessel ischemic stroke last known to be normal or well 6 to 16 hours and had a perfusion mismatch on imaging thrombectomy appeared to improve their functional independence and survival at 90 days. ■ Albers GW et. al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. PMID: ​ 29364767. ​ ○ Takeaways: ■ If we can get patients to centers where they are able to do endovascular interventions, it can lead to better outcomes in both function and survival ● Inform patients that meet study criteria of these additive benefits ● Learn what hospitals have endovascular capabilities so that post-tPA they can be transferred

Things I Do But Should I: Skin Tags Vanessa Cardy MD, Adrien Selim MD

Pearls: ● Acrochordon or skin tags are common benign pedunculated lesions that can be snipped off or frozen off. ● For hemostasis when snipping them off, consider silver nitrate or Monsel’s solution. ● For anesthesia, local lidocaine works but a faster and more effective option is ethyl chloride.

● Acrochordon (aka: skin tags): ​ ○ Benign skin-colored pedunculated lesion on a narrow stalk that vary in size from 1mm to 1cm ○ Found on 25-50% of adult population ○ Increase in frequency with age and occur in sites of friction, particularly the neck, axilla, inframammary and inguinal regions ○ Do not have to be removed but can be for cosmetic reasons or if they become a nuisance by getting caught on things (ie: jewelry or clothing) ○ Differential: ​ ■ If seen around perianal region, remember it could be a sign of Crohn’s disease ■ If seen with fibrofolliculomas (tumor of hair follicles) or trichodiscomas (tumor of hair disc) it may be a sign of Birt-Hogg-Dube syndrome ​ ​

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Source: Wikipedia ● Rare autosomal dominant disease characterized by non-cancerous skin tumors ○ Treatment Options: ■ Do nothing - they don’t have to be removed but often times patients request removal for cosmetic purposes ■ Snip and pull method: ​ ● : ○ Monsel’s solution: ferric sulfate provides rapid hemostasis ​ when applied to a small bleeding area. Helpful when snipping multiple small skin tags and best applied when the wound isn’t too wet with blood! ○ Silver nitrate: sticks will also help with bleeding but can lead ​ to skin pigmentation changes. ● Anesthesia: ​ ○ Lidocaine: may or may not use lidocaine solution to numb ​ the area but often times injecting each lesion hurts worse than just snipping the lesion ○ Ethyl Chloride: anesthetic spray that vaporizes immediately ​ on contact, cooling the skin and providing local anesthesia. Study in 2015 found it also improved antiseptic effect of betadine skin prep so there were less post-procedure complications. ○ Old versions of the spray were known to self-combust with reports of emergency doctors lighting patients on fire! Make sure to get the right spray. ● Cryotherapy: good for larger or numerous lesions ​

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Paper Chase #1 - Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes Andrew Buelt DO and Joe Weatherly DO

Bjerregaard LG et. al. Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes. N Engl J Med. 2018 Jun 28;378(26):2537-2538. PMID: 29949486. ​ ​

Pearls: ● If you don't want to have increased risk of diabetes, then lose the weight before the age of 13, otherwise the risk persists into adulthood. Start good habits early!

● Objective: determine whether the remission of overweight children before early ​ adulthood reduces the risk of diabetes. ● Background: More than 23% of children worldwide are obese or overweight. ​ ● Method: Cohort study of 62,000 Danish males where weight/height were measured at 7, ​ 13 and once between 17-26 years old. Using a health registry they found who had type II diabetes at 30 or older. ● Results: ○ If overweight in adulthood, more likely to develop type II diabetes (hazard ratio (HR) of 3.2) and increased (HR of 4.1) if you started overweight and remained overweight ○ If you were overweight that resolved by age 13, there was no increased risk of developing type II diabetes when compared to those who had never been overweight. ● Bottomline: If you don't want to have increased risk of diabetes, then lose the weight ​ before the age of 13, otherwise the risk persists into adulthood. Start good habits early!

Paper Chase #2 - Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Andrew Buelt DO and Joe Weatherly DO

Cipriani A et. al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. PMID: 29477251. ​ ​

Pearls:

Primary Care RAP August 2018 Written Summary | hippoed.com/pc 18 ​ ​

● Varied benefits of antidepressants. Amitriptyline was most effective for acute treatment of depression. Agomelatine and fluoxetine were the most acceptable and only ones with fewer dropouts than placebo.

● Objective: update on antidepressant effectiveness in acute depression and cross class ​ differences. ● Method: meta-analysis. ​ ● Results: ○ 82% of the included trials were at moderate to high risk of bias and the certainty of evidence was moderate to very low ○ Amitriptyline, mirtazapine, duloxetine, venlafaxine and paroxetine were among the most effective for acute depression ○ Fluoxetine was in the bottom four drugs for effectiveness but was one of the most acceptable drugs ○ Trazodone was both ineffective and poorly tolerated ● Bottomline: Varied benefits of antidepressants. Amitriptyline was most effective for acute ​ treatment of depression. Agomelatine and fluoxetine were the most acceptable and only ones with fewer dropouts than placebo.

Paper Chase #3 - Vest prevention of early sudden death trial Andrew Buelt DO and Joe Weatherly DO

Olgin JE. Vest prevention of early sudden death trial. Presented at the American College of Cardiology ​ conference, Orlando, FL, March 2018. ​

Pearls: ● The unpublished data from the trial demonstrated a statistically significant decrease in all-cause mortality but not in the primary endpoint - sudden cardiac death.

● Objective: determine if the wearable cardioverter defibrillator actually works ​ ● Background: Not yet published, this study was released at a major cardiology conference. ​ ● Method: randomized control trial of 2300 patients after acute MI with an ejection fraction ​ less than 35%. ○ 3 months follow-up during the 40 to 90 day waiting period for ICD placement after an MI ○ Primary endpoint: sudden death ● Results: ○ Sudden death occurred in 1.6% of those who wore vests and 2.4% in the control group → did not reach statistical significance ○ Overall mortality reached statistical significance (3.1% vs. 4.9%) in favor of wearing the vest ● Discussion:

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○ The vest is to prevent sudden death and did not do that. It also costs $10,000 for 3 months. It did, however, somehow lead to a decrease in overall mortality. ● Bottomline: The unpublished data from the trial demonstrated a statistically significant ​ decrease in all-cause mortality but not in the primary endpoint - sudden cardiac death.

Paper Chase #4 - A way to reverse CAD? Andrew Buelt DO and Joe Weatherly DO

Esselstyn CB Jr, Gendy G, Doyle J, Golubic M, Roizen MF. A way to reverse CAD? J Fam Pract. 2014 Jul;63(7):356-364b. PMID: 25198208. ​ ​

Pearls: ● Volunteer patients with CVD that sustained plant-based diets for a mean of 3.7 years, experienced a low rate of cardiac events with some seeing reversal in their coronary artery disease.

● Objective: long-term follow up on the effect of plant-based nutrition ​ ● Background: ● Method: cohort study of patients with CVD that were interested in starting a plant-based ​ diet ○ Diet: encouraged whole grains, legumes, lentils with vitamin B12/multivitamin supplementation; no meats, dairy or processed foods/oils. ● Results: ○ 89% adherence ○ Of the 117 patients that stuck to the diet, only one had recurrent stroke while of the 21 non-adherent patients, 13 had an adverse event ○ Vegan diets for about 3 years led to an 81% improvement in disease, 22% with disease reversal and no reported cardiac death ○ Among those who were non-adherent, 62% had worse disease after 3 years and 10% died from cardiac-related death ● Bottomline: Volunteer patients with CVD that sustained plant-based diets for a mean of ​ 3.7 years, experienced a low rate of cardiac events with some seeing reversal in their coronary artery disease.

Primary Care RAP August 2018 Written Summary | hippoed.com/pc 20 ​ ​

Paper Chase #5 - Association of E-Cigarette Use With Smoking Cessation Among Smokers Who Plan to Quit After a Hospitalization: A Prospective Study Andrew Buelt DO and Joe Weatherly DO

Rigotti NA et. al. Association of E-Cigarette Use With Smoking Cessation Among Smokers Who Plan to Quit After a Hospitalization: A Prospective Study. Ann Intern Med. 2018 May 1;168(9):613-620. PMID: ​ 29582077. ​

Pearls: ● If you want to quit smoking when you get out of the hospital, then it is best that you don't try to use E-Cigarettes as a crutch.

● Objective: Determine whether E-Cigarette use after hospital discharge is associated with ​ quitting smoking ● Background: E-cigarette use has increased significantly since 2010 with many adults ​ saying they are using it to help them reduce or stop smoking ● Method: randomized control trial of of 1300 hospitalized patients who smoked and ​ intended to quit after discharge. ○ Completed self-reported surveys at 1 and 3 months after discharge ○ Biochemical testing at 6 months ● Results: ○ At 3 months, 28% reported e-cigarette use. E-cigarette users were not as likely to refrain from smoking (10% refrained) at 6 months as non-users of e-cigarettes (26% refrained). ● Bottomline: If you want to quit smoking when you get out of the hospital, then it is best ​ that you don't try to use E-Cigarettes as a crutch.

SUMMARY Mailbag - Group A vs Group B Strep Throat Brandon Grove MD, Neda Frayha MD

Pearls: ● Mailbag discussion: Our reader posed a question about treatment of strep throat with Group B strep (GBS) positive culture. GBS is an uncommon pharyngeal pathogen but treatment may be considered if the patient is at increased risk of sequelae of GBS infection (ie: immunocompromised, contact with pregnant women/neonates/immunocompromised people).

● Mailbag Discussion: Strep throat treatment, especially group B strep positive culture ​ versus Group A strep positive cultures.

Primary Care RAP August 2018 Written Summary | hippoed.com/pc 21 ​ ​

○ Strep: ■ Strep are facultative (“capable but not bound to”) anaerobes, so they can make ATP with or without oxygen ■ Some strep have antigens that identify them - Group A and B. Others do not - strep pneumonia/mutans/viridans ■ Some strep hemolyze the blood on the blood agar petri dish leaving a clear strip where they have been smeared ○ Group A strep (pyogenes): ■ Cause many different diseases: strep pharyngitis, necrotizing fasciitis, toxic shock syndrome, immune-related scarlet fever and post-strep ■ Treatment is recommended to prevent peritonsillar , mastoiditis, and decrease spread to other contacts. ■ No treatment recommended for asymptomatic carriers. Noted these carriers can get recurrent viral pharyngitis. ○ Group B strep (GBS) ■ Asymptomatic carriers in GI and genital tract common → often checking pregnant women who then get prophylactic antibiotics to prevent pneumonia or in the newborn ■ Uncommonly causes pharyngeal infections but may cause sepsis, particularly in already sick patients. Positive blood cultures in a sick patient should warrant an ID consultation. ■ Consider treating if the patient is at risk of sequelae of GBS infection or in close contact with those who are at risk of sequelae of GBS infection (ie: pregnant women, neonates, immunocompromised people)

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