Primary Care RAP February 2019 Written Summary

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

Intro: Female Alopecia Aisha Lofters MD, Neda Frayha MD

Pearls: ● Androgenetic alopecia is the most common form of hair loss for both men and women. ● A good history and physical that includes examining the presence or absence of hair follicles is generally sufficient for diagnosis. ● For women, the only evidence-based treatment is topical 2% minoxidil.

● Hair follicle: ○ 3 stages ■ Anagen (growth), 80-90% of hair follicles should be in this state ■ Catagen (transition) ■ Telogen (resting) ○ Normal shedding is 100 hairs per day ● History of hair loss: ○ Duration - acute or chronic ○ Pattern - diffuse or one spot ○ Any changes - meds, diet ○ Family history ● Physical ○ Examine for erythema or or scaling ○ Examine follicles: are they present or are they absent (scarred) ○ Examine distribution of hair ○ Pull test: take about 60 hairs between thumb/index/middle fingers and give a pull. Negative ​ test is if 6 or fewer hairs come out in your hand which is consistent with normal shedding. Patient should not have washed hair for 24 hours. ○ Look for signs of androgen excess (acne, hirsutism) ● Diagnostics ○ indicated if you don’t see hair follicles and instead see scarring → punch biopsy can help diagnose , sarcoid, fungal or cancers. If biopsy nondiagnostic, start thinking about hereditary disorders or trauma (burns, radiation). ○ If androgen excess: total and free testosterone, DHEA, prolactin ○ Other labs: TSH, ANA, ferritin, VDRL, vitamin D ● Androgenetic alopecia ○ Most common form for men and women ○ In the presence of androgens, genes that shorten the anagen (growth) phase are going to be activated leading to less growth, shorter and thinner hair ○ Worse in frontal and parietal areas

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○ For women, not usually going to be lots of hormonal imbalance so doing hormonal workup is low yield unless other signs of androgen excess ○ No relation to frequency of washing hair ○ Treatment: ■ Minoxidil 2% - increases time follicles spend in growth phase, wakes up out of resting phase and enlarged the follicles themselves. ● One double-blind randomized control trial showed 50% had minimal hair growth and 13% and moderate hair growth compared to placebo ● Hair growth more pronounced at vertex than frontal areas ● Takes about 4 months to really show ● If patient stops taking it, hair loss resumes pretty quickly ● 5% dose more effective in men but shown to have more side effects in women (ie: more hair growth in other areas on the face). No good literature to support this dose in women. ■ Spironolactone - questionable data, consider in those with androgen excess ■ Finasteride - used in men but not women, especially of child-bearing age because of teratogenicity ■ Latanoprost - prostaglandin analog used for showing early data that it increases hair density but not mainstream ■ Transdermal injections of plasma rich in growth factor in Spain ■ Vitamins like biotin - no data substantiates their benefit. Biotin may impair thyroid assays ■ Hair transplant from one part of the scalp to another has good cosmetic outcomes but is expensive ● Other types: ○ Alopecia areata - autoimmune condition presents as well circumscribed oval patches of hair loss with exclamation point hairs at the periphery of the patch ■ Spontaneous recurrence and remission ■ Treated with intralesional steroids and topical anthralin cream ○ Telogen effluvium - diffuse hair loss caused by anything that shifts the follicles from anagen to telogen. Patients complain of lots of hair loss on pillow or in shower/tub ■ Common causes of stress, childbirth, hypothyroidism, severe infection, drugs (heparin, ACE inhibitors, anticonvulsants) ■ Hair will regrow on its own over time ○ Traumatic alopecia - traction from tight braiding or harsh brushes or trichotillomania

Reference: https://www.aafp.org/afp/2003/0301/p1007.html https://www.aafp.org/afp/2003/0701/p93.html https://www.aafp.org/afp/2009/0815/p356.html https://www.aafp.org/afp/2017/0915/p371.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582478/

Jacobs JP, Szpunar CA, Warner ML. Use of topical minoxidil therapy for androgenetic alopecia in women. Int J Dermatol. 1993;32:758–62. ​ ​

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DeVillez RL, Jacobs JP, Szpunar CA, Warner ML. Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution. Arch Dermatol. 1994;130:303–7. ​ ​ Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad ​ Dermatol. 2008 Oct. 59(4):547-66; quiz 567-8. ​ Motofei IG, Rowland DL, Baconi DL, et al. Androgenetic alopecia; drug safety and therapeutic strategies. Expert Opin Drug Saf. 2018 Jan 24. ​ ​ https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1610-0379.2011.07802.x http://jddonline.com/articles/dermatology/S1545961614P0809X/1

Asymptomatic Hypertension Matthew Delaney MD & Joe Martinez MD

Pearls: ❏ Blood pressure control is important, but it's most important in the longer term and patients can suffer adverse events if it is lowered too quickly.

Terminology: ● Hypertensive emergency - hypertension which causes end organ damage: ○ ACS - STEMI/NSTEMI ○ ○ Renal failure ○ Pulmonary edema ○ Encephalopathy or ○ Eclampsia ● Hypertensive urgency - patients with a systolic BP ≥180 or a diastolic ≥110 mmHg who are ​ minimally symptomatic or asymptomatic and have no evidence of end organ damage.

Management ● Patients who are truly asymptomatic and who are not at significant risk for developing rapidly progressive target organ damage should follow up with their PCP for blood pressure management. ● Evaluate for potential causes of elevated hypertension such as pain, substance withdrawal or rebound hypertension from stopping blood pressure medications. ● The American College of Emergency Physicians states that for asymptomatic patients with markedly elevated blood pressure, routine screening for acute target organ injury (eg, serum creatinine, urinalysis, ECG) and routine ED medical intervention is not required. ● There is overwhelming evidence that the short term risk of adverse events for patients with asymptomatic hypertension is exceptionally low and hospitalization is of no benefit:

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○ A 2016 JAMA study found that patients who were sent to the hospital for hypertensive urgency had similar rates of major adverse cardiovascular events (MACE) compared to those that were sent home. The rates of MACE in both groups was extremely low as well at ~1% (Patel et al, 2016). ○ A study published by Masood et al. in 2016 in the Annals of found that in a retrospective cohort of patients that were sent to the ED with asymptomatic hypertension only 8% were admitted. The risk of mortality was similar between the group sent home versus those that were admitted ( 1% within 90 days, 2.5% within a year, 4% in 2 years). ● In the entirety of the medical literature, there's never been a single study to show that abruptly reducing blood pressure is beneficial for patients that are asymptomatic, but there's been myriads of studies that show that it has the great potential to cause harm.

Reference: 1. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2527389 2. https://www.acep.org/patient-care/clinical-policies/asymptomatic-elevated-blood-pressu re/#sm.00000dnhqhmnuzf3guaxypz8x2i5z 3. http://journals.sagepub.com/doi/abs/10.1177/1060028016644756 4. 2017 Guideline for the Prevention, Detection, Evaluation, and ...

Personality Disorders Part 1 and 2: Tricks of the Trade Shawn Hersevoort MD, Mizuho Spangler DO

Pearls: ● Personality disorders are common in primary care. ● They are clustered into A (weird), B (wild) and C (worried). For A and B types, you may need to give less time. For C types, they may need more time to feel taken care of. In all instances, keep yourself safe (emotionally and physically) and document well. ● Other than dialectical behavior therapy for borderline personality disorders, there is no “treatment”. Accepting and working with these patients in- is probably the best approach.

● Personality - individual pattern of thoughts, emotions and behaviors which tend to be stable over ​ time ● Personality disorder - markedly inflexible deviation in personality from cultural norms that are ​ manifested in at least two areas (cognition, affect, interpersonal functioning and interpersonal control) and cause significant trouble/impairment, usually beginning by adolescence or early adulthood ○ About 4% in the US fit criteria for personality disorders ○ About 1% are severe

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○ Up to 10% in primary care settings with variation depending on type of primary care setting ○ Up to 50% in psychiatry settings ○ Up to 70% in the prison setting ○ Generally come from neglect, abuse, especially with cluster B ● Clusters: ​ ○ A (weird) ■ Paranoid ■ Schizoid ■ Schizotypal ○ B (wild) ■ Histrionic - dramatic and emotional, needs to get all the attention ■ Narcissistic - grandiose, has to be the ‘most’ ■ Borderline - labile and shifting mood, impulsive; often confused with bipolar disorder ■ Antisocial - love to violate rules and rights not because they’re labile ○ C (worried) ■ Avoidant ■ Dependent ■ Obsessive-compulsive ● “Difficult Patient” ○ Research term that is essentially synonymous with those with personality disorder ○ Multiple unexplained chronic and refractory symptoms that are disproportionately disabling ○ Poor treatment adherence ○ Emotional dysregulation ○ Make us feel like bad doctors ○ Insight varies ● Strategies for the difficult patient: ○ Get on the right side: “It’s going to be you and me versus the symptoms, the system.” ○ Acknowledge feelings without acknowledging they are right or wrong: “Wow, that sounds really frustrating. If any doctor didn’t listen to me, I’d be really angry, too.” ○ Don’t worry so much about diagnosis as patients are often in distress and not at their best. Instead, its most important to recognize something is wrong. ■ Treatment is a misnomer because mostly it is about managing and working with personality disorders ○ Make sure it is not you: are you angry about something that happened earlier? Are you tired or particularly stressed? ○ Remain calm, clear and professional ○ Avoid being abused and abusing ● Strategies for patients in cluster A: ○ Minimize time with them because social interaction makes them extremely uncomfortable ○ Consider increasing interval follow-up slightly because pushing too far can end up pushing them away ○ Try not to go to great lengths to get them on your side or have the most detailed history. They are not going to be able to give it to you ● Strategies for patients in cluster B: ○ Decrease contact time for self-preservation ○ Tolerate some level of rudeness but set clear boundaries/limits

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○ Rely on the textbook to defend your actions: “The standard of care for the symptoms you are describing is X, so I am not going to be able to offer the treatment you’re recommending because I don’t think it is safe and it is not recommended.” ● Strategies for patients in cluster C: ○ Increase contact time because they need to feel taken care of ○ Give them more information ○ Set limits: “Well, I’m still going to make the final recommendations here, and you can’t come in more frequently than I think is reasonable, although I’ll do my best to accomodate you.” ● Strategies for yourself as the provider taking care of these patients: ○ Be safe - patients can be emotionally and physically dangerous ○ Document well - most litigious patients. Especially cluster B and C patients that may meticulously document everything you have done. Important to document specific examples with quotes. ○ If patient cannot stop violating you or clinic rules, they need to go. Behavioral plans are important. ● Treatment for personality disorders: ○ Best to keep in-house and try to manage co-morbid conditions ○ Exception is borderline personality disorder where dialectical behavioral therapy is effective

Reference: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.

Bateman AW, Gunderson J, Mulder R. Treatment of personality disorder. Lancet 2015; 385(9969):735-43.

Leichsenring F, Leibing E. The effectiveness of psychodynamic therapy and cognitive behavior therapy in the treatment of personality disorders: a meta-analysis. Am J Psychiatry 2003; 160:1223.

Leichsenring F, Rabung S. Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. JAMA 2008; 300:1551.

Tyrer P, Reed GM, Crawford MJ. Classification, assessment, prevalence, and effect of personality disorder. Lancet 2015; 385(9969):717-26.

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Eosinophilia Tom Robertson MD, Neda Frayha MD

Pearls: ● Don’t brush off eosinophilia, especially in asthmatic patients. ● If elevated eosinophils think: , medications, . ● Strongyloides (common in immigrant populations) and aspergillus are two infections that can lead to eosinophilia.

● Eosinophils: ○ White blood cells found mostly in tissue and not circulating blood ○ Eosinophilia plays a part in the immune response but dysregulation can wreak havoc on tissue leading to fibrosis, thrombosis, and pathologic inflammation ○ Normal eosinophil count is 50 to 500 ○ Eosinophilia (take % eosinophils x total WBC to get absolute eosinophils) ■ Mild = 500 - 1500 ■ Moderate = 1500 - 5000 ■ Severe > 5000 ● Symptoms and findings in eosinophilia: ○ Fatigue ○ Myalgias ○ Cough, dyspnea, wheezing ○ ○ Rash, hyperpigmentation ○ Diarrhea ○ Lymphadenopathy ○ Signs of allergies ● Warrants further testing: ○ 1. Moderate eosinophilia ○ 2. Mild eosinophilia with signs of organ involvement (rash, elevated , abnormal chest x-ray) ○ 3. Mild eosinophilia with a history of travel to parasite endemic areas ● Differential: ○ Clonal - resulting from hematologic malignancy → refer to hematology ○ Reactive - underlying pathology is causing immune response ■ Allergens - in western world, accounts for 80% of eosinophilia, majority are mild to moderate, may have some prognostic value in asthmatics ● Drugs (antibiotics, antiepileptics, NSAIDs, xanthine oxidase inhibitors) ● ■ Infection - parasites, helminths, fungus ● Strongyloides: non-specific abdominal or pulmonary symptoms, up to 46% of immigrants in the US tested positive, rule out before giving steroids because immunocompromise can lead to disseminated infection ● Aspergillus: may cause allergic bronchopulmonary aspergillosis in those with underlying lung disease

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■ Malignancy - up to 7% solid organ malignancies and 20% of hematologic malignancies may result in eosinophilia ■ Connective tissue disease - eosinophilic granulomatosis with polyangitis (ie: Churg-Strauss), Addison’s, lupus, sarcoid ● Work-up: ○ CBC with differential trend ○ Peripheral smear ○ BMP for creatinine ○ LFT for liver function ○ Troponin for signs of myocarditis ○ Serologies for strongyloides ○ Quantitative immunoglobulins, especially IgE levels as that is elevated in atopy ○ HIV ○ If pulmonary symptoms: chest x-ray, PFTs, aspergillus ○ If entire work-up negative, refer to hematology

Reference: 1. Montgomery ND, Dunphy CH, Mooberry M, et al. Diagnostic complexities of eosinophilia. Arch Pathol Lab Med. 2013 ​ Feb;137(2):259-69

2. Kamfar HZ, Koshak EE, Milaat WA: Is there a role for automated eosinophil count in severity assessment. J Asthma 1999; 36(2):153-158.

3. Ulrik CS, Frederiksen J: Mortality and markers of risk of asthma death among 1,075 outpatients with asthma.. Chest 1995; 108:10-15.

4. Masi AT, et al. The American College of 1990 criteria for the classification of Churg-Strauss Syndrome. ​ Arthritis Rheum. 1990 Aug;33(8):1094-100.

5. Isaacson NH, Rapoport P. Eosinophilia in malignant tumors; its significance. Ann Intern Med. 1946;25(6):893–902. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​

6. Vaughan Hudson B, Linch DC, Macintyre EA, et al;British National Lymphoma Investigation. Selective peripheral blood eosinophilia associated with survival advantage in Hodgkin's disease (BNLI report no 31). J Clin Pathol. ​ ​ 1987;40(3):247–250.

7. Murata K, Yamada Y, Kamihira S, et al. Frequency of eosinophilia in adult T-cell leukemia/lymphoma. Cancer. ​ ​ 1992;69(4):966–971.

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It's the System: Organizational Strategies for Burnout Aisha Lofters MD, Neda Frayha MD

Pearls: ● Organizations can put in place strategies to combat burnout that include acknowledging burnout, encouraging team-based care, protecting time for wellness and administrative work, and supporting those who do feel burned out.

● Burnout is a specific syndrome characterized by a high degree of emotional exhaustion, depersonalization and a low sense of personal accomplishment in the work environment ○ About 50% of physicians in the US report significant levels of burnout with primary care providers towards the top ○ The Institute for Healthcare Improvement highlights one issue in medicine being the focus on self-sacrifice instead of on personal wellness ● Strategies for organizations to combat physician burnout: ○ 1. Acknowledge that burnout exists ■ Develop wellness committees that have the same stature and respect as others ■ Survey staff to get a sense of wellbeing and be prepared to act on it ○ 2. Encourage team-based care ■ Distribute administrative tasks ■ Team huddles ○ 3. Protect time for support and wellness ■ Balint groups: regular meeting during protected time of 6-10 members and a trained external facilitator for a conversation around an interpersonal issue. These groups have been shown to increase provider’s ability to cope ○ 4. Support leave time ■ Floating locums can help fill gaps when there are leaves ○ 5. Support and expectation to unplug from the EMR ○ 6. Protected administrative time ○ 7. Involve professionals in major and minor organizational decisions to give back a sense of control ○ 8. Clear and well-publicized process of what to do if feeling burnout

Reference: https://news.aamc.org/medical-education/article/fight-burnout-medical-faculty-foster-resilience /?utm_source=newsletter&utm_medium=email&utm_campaign=AAMCNews031418#.WqlK8q5 TV0w.email http://www.ihi.org/education/IHIOpenSchool/resources/Pages/CaseStudies/DealingWithBurnou t.aspx http://www.nejm.org/doi/full/10.1056/NEJMp1716845 https://www.cma.ca/Assets/assets-library/document/en/practice-management-and-wellness/1- Keynote-Shanafelt-e.pdf#search=burnout

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http://www.nejmcareercenter.org/article/targeting-physician-burnout-/ http://www.cfp.ca/content/58/3/245 https://hbr.org/cover-story/2017/01/beat-generosity-burnout https://www.medscape.com/features/slideshow/lifestyle/2017/overview https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2532788 ​ https://www.ahrq.gov/professionals/clinicians-providers/ahrq-works/burnout/index.html http://policybase.cma.ca/dbtw-wpd/Policypdf/PD18-01.pdf https://nam.edu/initiatives/clinician-resilience-and-well-being/

Maslach Burnout Index manual

Sinsky C, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: a time and motion study in 4 specialties. Ann Intern Med 2016;165:753-760.

Shanafelt TD, Hasan O, Dyrbye LN, et al. Changes in burnout and satisfaction with work-life balance in physicians and the general US working population between 2011 and 2014. Mayo Clin Proc 2015;90:1600-1613.

Panagioti M, Panagopoulou E, Bower P, et al. Controlled interventions to reduce burnout in physicians: a systematic review and meta-analysis. JAMA Intern Med 2017;177:195-205. Physician burnout is a public health crisis: a message to our fellow health care CEOs. Health Affairs Blog. March 28, 2017 (https://www.healthaffairs.org/action/showDoPubSecure?doi=10.1377%2Fhblog20170328.05939 ​ 7&format=full). ​ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495474/

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DOAC Reversal Tarlan Hedayati MD, Matthieu Delaney MD & Neda Frayha MD

Pearls: ❏ Direct oral anticoagulants are becoming popular choices for patients needing anticoagulation and we need to be comfortable reversing these agents. ❏ For patients with life threatening bleeding, know that the evidence supporting the use of these specific reversal agents is poor but may be the only option you have in treating these patients.

BACKGROUND ● There are two types of direct oral anticoagulants: the direct thrombin inhibitors (i.e. dabigatran) and factor Xa inhibitors (i.e. rivaroxaban, apixaban, edoxaban). ● The benefit to these oral anticoagulants is that there is a fixed dose regimen, they don’t need frequent lab checks (ex. INR), there is no need for bridging and there are few dietary restrictions. ● The downside is that they can be difficult to reverse, we can’t directly measure their anticoagulant effects and because some are renally cleared it requires extra caution in patients with CKD. ● There is a decreased risk of intracranial hemorrhage with DOACs compared to warfarin but a higher chance of GI bleed.

GENERAL MANAGEMENT 1. Send labs including CBC, BMP (to assess renal function), coagulation studies (PT/INR, PTT), type & screen. 2. Transfuse patient with blood products (based on blood loss, hemodynamic instability, etc). 3. Give 4 Factor PCC, if available, to reverse anticoagulants. It is preferred over FFP because it is rapidly available, works faster, does not requiring thawing and is a smaller volume. 4. Consider giving a specific reversal agent if available.

DABIGATRAN ● The specific reversal agent for dabigatran is idarucizumab. ● Two prior papers that looked at the use of idarucizumab for the treatment of uncontrolled bleeding raised serious questions regarding its true efficacy. ● Ultimately, if you have a sick patient with life-threatening bleeding who is on dabigatran, consider using 4 factor-PCC and, if available, idarucizumab until we have better information on how to best control bleeding in these patients.

APIXABAN + RIVAROXABAN (-XABANS) ● The specific reversal agent for the -xabans is andexanet alfa. ● Andexanet alfa was recently approved, expensive antidote that, much like idarucizumab, shows questionable results in the trials used to get the drug approved.

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References: ● Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016;375(12):1131-41. ● Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015;373(25):2413-24. ● Pollack CV, Reilly PA, Van ryn J, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017;377(5):431-441. ● Almegren M. Reversal of direct oral anticoagulants. Vasc Health Risk Manag. 2017;13:287-292. ●

Reference: 1. https://www.nejm.org/doi/full/10.1056/NEJMoa1607887 2. https://www.nejm.org/doi/full/10.1056/NEJMoa1510991 3. https://www.nejm.org/doi/full/10.1056/NEJMoa1707278 4. https://www.ncbi.nlm.nih.gov/pubmed/28769570

Starting OCPs Molly Heublein MD, Neda Frayha MD

Pearls: ● Four steps to starting OCP’s: ○ 1. Review medical contraindications: CDC Medical Eligibility Criteria (MEC) is the gold standard ○ 2. Choose a dose of estrogen: usually 30-35mcg ○ 3. Choose a progesterone: older generation are more androgenic ○ 4. Choose phase: monophasic is standard, triphasic has no real benefit

● 1. Review medical contraindications: ○ Look to the CDC Medical Eligibility Criteria (MEC), gold standard ● 2. Choose a dose of estrogen: ○ In the US, only ethinyl estradiol ■ Low dose = 20mcg → consider if she has had problems before with too much estrogen like breast tenderness, bloating, nausea ■ Standard dose = 30mcg → generally first-line ■ High dose = 50mcg ● 3. Choose a progesterone ○ Many options in the US divided into generation ■ First generation → more androgenic sides effects like acne, anxiety, hirsutism ■ Newer generation → less androgenic ○ Start with a newer generation like levonorgestrel or norgestimate ○ Contraception Point of Care is a great app with all the different OCPs ​

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● 4. Choose monophasic vs. triphasic vs. extended-cycle pill ○ Monophasic: same dose of estrogen and progesterone throughout the month with standard ​ 21 to 24 days of active hormone ○ Triphasic: fluctuating levels of hormone to more closely mirror natural hormone levels → ​ no real proven benefit ○ Extended cycle: three months of active pills and then one placebo week → most ​ bothersome symptom is spotting or breakthrough bleeding but otherwise is safe ● Other notes: ○ OCP’s are pretty forgiving. If you miss one day, just take the pill you missed even if that means taking two pills in one day. If you’ve missed two pills, then you may have ovulated and you should use some other method of contraception for 7 days. ○ Breakthrough bleeding is not uncommon when starting OCP’s in the first couple of cycles. It also happens if the pill is taken irregularly. Some treatment options: ■ Ibuprofen 800mg for 1-2 weeks for is often effective ■ May add extra estrogen 0.5 to 0.1mg daily for 1-2 weeks ■ Trial a different progesterone or higher progesterone ○ Progesterone-only pill: ​ ■ Upsides: safe in everyone except those with current or recent diagnosis of breast cancer ■ Downsides: Works by thickening and decreasing cervical mucus, and does not reliably suppress ovulation. Really needs to be taken within 3-hour window and if not, back-up contraception should be used within 2 days. ■ Continuous active pack, no placebo pills ■ Common side effect is irregular spotting, lighter periods and missed periods

Reference: Contraceptive Use in the United States, Fact Sheet, Sept 2016. Guttmacher Institute. www.guttmacher.org/fact-sheet/contraceptive

Steinberg, Joshua, MD. “Contraception Point-of-Care”. Apple App Store, Version 1.2.

Center for Disease Control. “Contraception, US MEC, US SPR”. Apple App Store, Version 2.0.3

Weill, Alain, et al. “Low Risk Oestrogen Combined Oral Contraception and Risk of Pulmonary Embolism, Stroke, and Myocardial in Five Million French Women: Cohort Study”. BMJ May 2016: 353.

Schrager, Sarina. “Abnormal Uterine Bleeding Associated with Hormonal Contraception”. American Family Physician. 2002 May 15;65(10):2073-2081. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268863/

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Polymyalgia Rheumatica Matthew Delaney MD & Jeff Holmes MD

Pearls: ❏ Consider as potential predisposing condition that may cause falls in the elderly patient population.

Elderly Falls ● One of the most common reasons the elderly present is for a fall. ● In the Urgent Care setting, falls that are not preceded by prodromal symptoms (i.e. sudden onset , acute abdominal pain, or lightheadedness) are labeled as a mechanical fall. This does our patients a disservice because it prevents us from considering what factors may have made the patient more susceptible to falling in the first place. ● We should consider other medical conditions such as polymyalgia rheumatica as potential reasons why elderly patients fall.

Polymyalgia Rheumatica ● Polymyalgia rheumatica is a common, chronic inflammatory rheumatic disease that's characterized by muscle pain and stiffness particularly in the neck, and hips. ● Contrary to its name, it's not a myopathic process (a problem with the muscles). It's actually a condition that affects proximal articular and periarticular structures including the joints, the bursa and the tendons of the hips and the shoulders. ● PMR is second only to as a systemic rheumatic disease in adults and is a significant cause of disability and falls. ● Interestingly, 20% of patients with PMR have associated increased risk of stroke, MI and , a potentially vision threatening diagnosis that affects the ophthalmic arteries. ● This condition is particularly responsive to steroids so if we can catch this in the patient's history and make the diagnosis, we can significantly improve the patient’s short and potentially long-term outcomes.

Presentation ● There's no universally accepted diagnostic criteria. Consider in patients who present over 50 with symptoms that involve aching and stiffness in their upper arms, posterior neck, pelvic girdle and their lumbar region. ● Symptoms are all worse in the morning or after periods of inactivity and that's called “gelling.” It is a hallmark of synovitis in systemic rheumatic disease in general. ● Simple screening questions: ○ Do you have trouble standing due to pain? ○ Have you required assistance with morning dressing? ○ For women, do you have trouble hooking your bra in the back? ○ Do you have any trouble putting on your coat?

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Diagnosis ● Making the diagnosis involves ordering both an ESR and a CRP. ● Studies have shown the sed rate in PMR can be less than 40 in roughly 20% of patients. By ordering both the ESR and the CRP, you greatly improve the sensitivity. ● The rate of patients who have PMR but have negative ESR and negative CRP, is 0.5 to 1.5%. ● When you're screening a patient that you are concerned has PMR, also evaluate your patient for . ○ Giant cell arteritis is a syndrome of a that commonly affects branches of the carotid arteries and is potentially vision threatening. ○ Symptoms may include a unilateral headache, sometimes bilateral, jaw , scalp tenderness, and unfortunately blindness if this goes on too long. ● 40-60% of patients with giant cell arteritis will have PMR symptoms at the time of diagnosis and up to 20% of patients with PMR will also have giant cell arteritis.

Treatment ● Start 10 to 20 milligrams per day for patients with PMR and with giant cell arteritis 40 to 60 milligrams per day. ● Patients with suspected GCA should be referred for a temporal artery biopsy. ● Don't delay your steroids and your therapy waiting for the biopsy.

REFERENCES: 1. Kermani TA, Warrington KJ. Polymyalgia rheumatica. Lancet. 2013 Jan 5;381(9860):63-72, correction can be found in Lancet. 2013 Jan 5;381(9860):28. 2. Dejaco C, Singh YP, Perel P, et al. European League Against Rheumatism., American College of Rheumatology. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheumatol. 2015 Oct;67(10):2569-80

Paper Chase #1 - Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis Steve Biederman MD, Tom Robertson MD

Iversen K et. al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2018 Aug 28. doi: 10.1056/NEJMoa1808312. PMID: 30152252. ​ ​

Pearls: ● Changing to oral antibiotics is non-inferior to IV antibiotics in patients with left-sided endocarditis.

Primary Care RAP February 2019 Written Summary | hippoed.com/pc 15 ​ ​

● Objective: investigate if patient with infective endocarditis who was stabilized with IV ​ antibiotics could be transitioned to PO antibiotics. ● Mortality from endocarditis is 15-45%, with the bulk of that risk early in treatment. Hypothesized patients who are clinically stable could transition to oral antibiotics instead of completing a full 6- week course. ● Study: multicenter, randomized, un-blinded, non-inferiority trial. ​ ○ Inclusion criteria: adult in stable condition (no valvular abscess, afebrile for days, no elevation in inflammatory markers), left-sided endocarditis by Duke criteria, blood cultures with strep, enterococcus faecalis, staph aureus or coagulase negative staph. Received 10 days of IV antibiotics. ○ Primary outcomes: all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteremia ○ Followed for 6 months ● Primary composite outcome occurred in 12.1% in the IV treated group and in 9.0% in the orally treated group, which met noninferiority criteria ● Not completed in the US, no one in study had MRSA and only 5 IV drug users ● Bottomline: Changing to oral antibiotics non-inferior to IV antibiotics in patients with ​ left-sided endocarditis.

Paper Chase #2 - Efficacy of Telemedical Interventional Management in Patients with Heart Failure (TIM-HF2) Steve Biederman MD, Tom Robertson MD

Koehler F et. al. Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial. Lancet. 2018 Sep 22;392(10152):1047-1057. Doi: 10.1016/S0140-6736(18)31880-4. PMID: 30153985. ​ ​

Pearls: ● Remote telemedical intervention reduced hospital admission days and/or all-cause mortality across both urban and rural settings.

● Objective: Assess whether telemedical interventions impact hospital readmission or ​ mortality in heart failure patients. ● Study: prospective, multicenter, randomized control trial done in Germany. Patients in the ​ telemedicine group were given 3 lead EKG, blood pressure cuff, weight scale, pulse ox and mobile phone. All these devices were connected to hub available 24/7 to patients. ○ Primary outcome: unplanned hospital admission, all-cause mortality ● Bottomline: Remote telemedical intervention reduced hospital admission days and/or ​ all-cause mortality across both urban and rural settings.

Primary Care RAP February 2019 Written Summary | hippoed.com/pc 16 ​ ​

Paper Chase #3 - Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients with Subclinical Hypothyroidism Steve Biederman MD, Tom Robertson MD

Feller M et. al. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018 Oct 2;320(13):1349-1359. doi:10.1001/jama.2018.13770. PMID: 30285179. ​ ​

Pearls: ● Among non-pregnant adults with subclinical hypothyroidism, therapy was not associated with improvements in general quality of life or thyroid-related symptoms.

● Meta-analysis of randomized control trials that all studied the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism. ● Bottomline: Among non-pregnant adults with subclinical hypothyroidism, therapy was not ​ associated with improvements in general quality of life or thyroid-related symptoms.

Paper Chase #4 - Statins for Primary Prevention of Cardiovascular Events and Mortality in Old and Very Old Adults with and without Type 2 Steve Biederman MD, Tom Robertson MD

Ramos R et. al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018 Sep 5;362:k3359. PMID: ​ 30185425. ​

Pearls: ● Statin treatment was associated with reductions in the incidence of atherosclerotic CVD and all-cause mortality only in groups of elderly patients aged 75 to 84 with diabetes.

● Objective: assess whether statin treatment is associated with reduction in atherosclerotic ​ coronary vascular disease and mortality in elderly adults with and without diabetes. ● Retrospective cohort of 46,000 patients stratified into groups of diabetes or no diabetes, 75 to 84, over 84. Followed them for 8 years. ● Findings: ​ ○ Statin use benefited mortality and CVD risk in 75 to 84 year-olds with diabetes by 16% and 24%. ○ Statin use was not associated with increase in adverse events like myopathy or liver disease. ● Bottomline: statin treatment was associated with reductions in the incidence of ​ atherosclerotic CVD and all cause mortality only in groups of elderly patients aged 75 to 84 with diabetes.

Primary Care RAP February 2019 Written Summary | hippoed.com/pc 17 ​ ​

Paper Chase #5 - Evaluation of Galcanezumab for the Prevention of Episodic (EVOLVE-1 RCT) Steve Biederman MD, Tom Robertson MD

Stauffer VL et. al. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. PMID: 29813147. ​ ​

Pearls: ● Monthly galcanezumab injections provide a clinical benefit and improved functioning in terms of reduced headache days per month (about 2 days per month less ), reduced use of acute migraine medications and patient symptom scores with low incidence of adverse effects.

● Galcanezumab is a monoclonal that binds to the calcitonin gene receptor peptides that are implicated in . ● Phase 3 multicenter double blind, placebo-controlled, randomized control trial comparing galcanezumab versus placebo in adult patients with migraines 4-14 times per month. Patients could not take their preventative medications but could take their abortive medications. Received drug for 6 months and then followed for another 5 months. ● Bottomline: monthly galcanezumab injections provide a clinical benefit and improved ​ functioning in terms of reduced headache days per month (about 2 days per month less headaches), reduced use of acute migraine medications and patient symptom scores with low incidence of adverse effects.

Primary Care RAP February 2019 Written Summary | hippoed.com/pc 18 ​ ​