Primary Care RAP December 2018 Written Summary Editor-in-Chief: Neda Frayha MD

Associate Editor: Kenji Taylor MD, MSc

Intro - Clots and OCPs Rob Orman MD, Neda Frayha MD Pearls:

Overall progesterone-only contraceptive methods are safer from a thrombosis risk perspective than those containing estrogen.

OCP’s and clotting risk:

Is cardiolipin level a risk factor? It depends on the level and prior history of thrombosis.

Cardiolipin antibody (IgM) is considered positive when greater than 40 If positive titers and history of thrombosis, OCPs are contraindicated If positive titers and no history of thrombosis, gray zone but best to avoid

estrogens → progesterone contraceptive Is better choice If a patient has a spontaneous DVT while on OCP, are they off for life?

If it was an estrogen OCP, not safe to continue because recurrence is high Progesterone-based contraceptives are safe. Some data suggests Depo

(progesterone-based) may be thrombogenic What is the risk of thrombosis with OCP’s?

Cochrane review in 2014 compared OCP users to controls and found relative risk was 3.5. The lowest risk was found in those who used ethinylestradiol 30mcg and levonorgestrel. In most patients they are both safe and effective.

Reference: https://www.cochrane.org/CD010813/FERTILREG_contraceptive-pills-and-venous-thrombosis https://www.medscape.com/viewarticle/710116 https://www.ncbi.nlm.nih.gov/pubmed/2960241 The Venous Thrombotic Risk of Oral Contraceptives, Effects of Oestrogen Dose and Progestogen Type: Results of the MEGA Case­Control Study. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. BMJ. 2009;339:b2921

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Hypertensive Disorders of Pregnancy Megan Jones MD, Neda Frayha MD Pearls:

The key to hypertensive disorders in pregnancy is getting the appropriate history and knowing the criteria for diagnosis, which impacts management and timing of delivery.

The four types of disorders are: chronic hypertension, gestational hypertension, preeclampsia/preeclampsia with severe features and chronic hypertension with superimposed preeclampsia.

Why is hypertension in pregnancy important?

Mom - hypertension is one of the top three causes of mortality in the US. Women with hypertension in pregnancy have increased rates of chronic hypertension, type 2 diabetes and hyperlipidemia for decades after delivering

Baby - may lead to intrauterine growth restriction and fetal demise

Hypertension in pregnancy = >140/90 on two separate occasions at least 4 hours apart

1. Chronic Hypertension: hypertension prior to 20 weeks gestation 2. Gestational hypertension: hypertension after 20 weeks gestation 3. Preeclampsia: hypertension >140/90 on two separate occasions or >160/110 confirmed

over shorter interval AND Proteinuria (300mg in 24 hours) OR One of the following:

Thrombocytopenia Impaired renal function Impaired liver function Pulmonary edema Cerebral/visual symptoms

Preeclampsia with severe feature: >160/110, symptoms of headache/right upper quadrant pain/vision changes, labs consistent with HELLP syndrome

4. Chronic hypertension with superimposed preeclampsia: challenging to diagnose but important to differentiate because the preeclampsia piece can quickly progress

Evaluation for those with chronic hypertension : CBC, BMP, AST/ALT, 24-hour urine protein Repeat labs if you have are concerned they are developing preeclampsia

Treatment: For those with chronic hypertension, blood pressure tends to improve in the first 20 weeks

of pregnancy. Nifedipine and labetalol are oral agents used and initiated after 34 weeks Goal is keeping people in the 140/90’s but certainly below 160/110 See patient monthly to make sure blood pressure is under control Fetal anatomy and growth scans started at 20 weeks every 4-6 weeks to make sure fetus is

growing well By 32 weeks and beyond, twice weekly antenatal testing (nonstress test or biophysical

profile) weekly. May do earlier if they have significant hypertension. Also weekly labs. Delivery Management:

Chronic hypertension: 38-40 weeks depending on the guidelines and how well-controlled

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Gestionational hypertension and preeclampsia: 37 weeks to avoid stillbirth Preeclampsia with severe features: monitoring in hospital, blood pressure control and

delivery at 34 weeks if possible. Reference: ACOG Practice Bulletin 33: Diagnosis/ Management Preeclampsia and Eclampsia [January 2002] ACOG Practice Bulletin 125: Chronic HTN in Pregnancy [July 2001] Obstetric Intensive Care Manual: 3rd edition. Foley, MR, T Strong, T Garite. 2011. Management of hypertension in pregnant and postpartum women. P August. UpToDate.com. 2012. Hypertension in Pregnancy. ACOG, SMFM, AAFP. Task Force. 2013. Stuart JJ, Tanz LJ, Missmer SA, et al. Hypertensive disorders of pregnancy and maternal cardiovascular disease risk factor development. Ann Intern Med 2018; 169:224-232. doi:10.7326/M17-2740.

Pediatric Stroke Emily Rose, MD and Mizuho Morrison, DO

Pearls: The etiologies of pediatric stroke differ from adults and 50% of pediatric strokes are

ischemia and 50% are hemorrhagic. The most common underlying etiologies include sickle cell disease, infection, Moyamoya, and inflammatory disorders.

tPA is not currently approved for treatment of pediatric ischemic stroke. If stroke is suspected, urgent referral to a pediatric stroke center is of utmost

importance.

How common are pediatric strokes? Pediatric strokes are more common in children than brain tumors. It is one of the top 10 causes of pediatric mortality.

What type of strokes do children get? Unlike adults in which about 80% of strokes are ischemic, pediatric strokes are about 50/50 with respect to ischemic and hemorrhagic.

What is the presentation of pediatric stroke? Not unlike adults, children can present with hemiplegia or some focal neurological deficit plus/minus altered mental status. This differential is more common of other conditions that children get; for example, Todd’s paralysis or hemiplegic migraine.

What are the main etiologies of pediatric stroke? Underlying sickle cell disease is the most important risk factor for pediatric stroke,

increasing the risk of stroke by 10-11 times more than the general population. 11% of children with sickle cell disease will have some evidence of stroke by age 20. Most of these occur before the age of 10. The mechanism for stroke in these patient is likely related to inflammation in the arteries. The same pathophysiology can be seen in rheumatologic conditions leading to stroke.

Infection is another important risk factor. The mechanism here is infection that directly erodes and inflames the venous sinus, leading to thrombosis and stroke. Children who are already hypercoagulable are at greater risk for this. In addition to this direct extension, global infection, such as varicella, can lead to arteriopathies and stroke.

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Moyamoya (“puff of smoke” in Japanese) is a progressive cerebrovascular disorder leading to stenosis and ischemia, usually of the distal carotids, which leads to stroke. A child can have Moyamoya disease or syndrome (with SLE, for example). Because of the bilateral nature of the disease, children will present with episodes of alternating hemiplegia.

Inflammatory disorders, such as Kawasaki, SLE, Wegner’s, to name a few, can lead to arteriopathies and vasculitis, increasing the risk of stroke.

Stroke can happen at any age, but the presentations may vary based on age. What conditions are in the differential when thinking of stroke? In addition to what has

been mentioned above (Todd’s paralysis and hemiplegic migraines), hypoglycemia, seizure, malingering/conversion disorder, meningoencephalitis, Bell’s palsy and/or other focal neurologic deficits.

If stroke is suspected, what is your outpatient management? Immediate referral to a stroke center is key; as these centers will be able to aid in a complete history, detailed neuro examination and advanced imaging quickly.

Given the 50/50 breakdown of ischemic/hemorrhagic stroke, as above, a rapid 15 min stroke MRI is the best imaging modality. In most stroke centers, the neuroradiologist will read these MRIs in real time and can add an MRA if needed.

If an MRI is not available, a CT scan should be completed to assess for hemorrhage.

Is there evidence for the use of tPA in pediatric stroke? The short answer is that tPA is not recommended in children; it is an off label use. The official recommendation from the Neurological Society states this. That said, it is being used a lot off-label in the community.

tPA is used for embolic ischemic stroke, and most kids do not have this. tPA is only beneficial if you apply the criteria for adults, so it has to be ideally given within three hours. Giving it up to 4 ½ hours after symptom onset might also be OK. Given the significant side effects and off-label use, tPA should always be given in conjunction with a neurologist.

Other forms of anticoagulation, such as aspirin or heparin, are also controversial. Many centers have pediatric stroke protocols in place, however, the data is not

overwhelmingly convincing to support one protocol over another.

NOTALGIA and MERALGIA PARESTHETICA Molly Heublein MD Pearls:

Notalgia (back) paresthetica and meralgia (thigh) paresthetica are bothersome sensory conditions that are generally benign. First-line treatment would be reassurance followed by topicals (capsaicin, lidocaine).

Notalgia paresthetica:

Definition: Greek for “abnormal sensory sensations of the back”. Neuropathic itch in the lower two thirds of the medial scapula

Presentation :

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Often presents as subacute or chronic itching localized to that area. May also have some numbness, tingling, temperature changes or foreign body sensation

May be a normal exam or some secondary changes due to itching Typically affects middle-aged women around age of 50 with unknown prevalence

Etiology : unknown perhaps spinal nerve entrapment or peripheral neuropathy Associated with endocrinopathies like MEN2 (medullary thyroid cancer,

parathyroid tumors and pheochromocytoma) Treatment :

Reassurance is often all that is necessary Topicals (capsaicin, lidocaine, tacrolimus) Oral medications (gabapentin, oxcarbazepine) Botox injections may help Physical therapy Steroid injection blocks Neurosurgical decompression (rare and in very severe cases)

Meralgia paresthetica: Definition: neuropathic pain in the lateral aspect of the thigh Etiology : caused by entrapment of the lateral cutaneous nerve Presentation :

Painful burning, buzzing or sensory loss sensation over the anterolateral aspect of the thigh

May be worse with walking as a result of changes in tension around the nerve Middle-aged people between 40-50 and more common in men

Etiology : Obesity, pregnancy, tight clothes, diabetes, hypothyroidism, alcoholism, pelvic surgeries, appendectomies and lumbar spine surgeries have all been attributed to irritating the nerve

Exam : Accompanied by abnormal sensory findings that can worsen with hip extension. May also have lateral inguinal ligament tenderness and hair loss from constant

rubbing. “Pelvic compression test”: patient lays laterally on asymptomatic hip while you

apply downward pressure force to the pelvis for about 45 seconds. Positive test is resolution of symptoms because the pressure should relax the inguinal ligament.

95% sensitive and 93% specific in one small series in comparison to evoke potentials

“Nerve block test”: injection of lidocaine into the site where the lateral cutaneous nerve exits the pelvis at the inguinal ligament. Positive if symptom relief that lasts for 30-40 minutes after injection

Reference: Donal Harney, Jacob Patijn; Meralgia Paresthetica: Diagnosis and Management Strategies, Pain Medicine, Volume 8, Issue 8, 1 November 2007, Pages 669–677, https://doi.org/10.1111/j.1526-4637.2006.00227.x Robbins BA, Ferrer-Bruker SJ. Notalgia Paresthetica. [Updated 2017 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470597/ Howard, M. , Sahhar, L. , Andrews, F. , Bergman, R. and Gin, D. (2018), Notalgia paresthetica: a review for dermatologists. Int J Dermatol, 57: 388-392. doi:10.1111/ijd.13853

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Cheatham SW, Kolber MJ, Salamh PA. MERALGIA PARESTHETICA: A REVIEW OF THE LITERATURE. International Journal of Sports Physical Therapy. 2013;8(6):883-893.

TREMOR Part 1 and 2: Diagnosis and Treatment Paul Simmons MD, Neda Frayha MD Pearls:

Tremor is very common in primary care and can be broken up into 5 categories: physiologic, essential, parkinsonian, toxic/metabolic and cerebellar.

Essential tremor is worse with action while parkinsonian is at rest. A cerebellar tremor is a severe intention tremor and is red flag for a nervous system

lesion that warrants further investigation. Treatment of essential tremor is not curative but focused on symptom management.

Tools include PT/OT, moderate alcohol for social situations, medications (propranolol, primidone, topiramate) and deep brain stimulation or thalamotomy for severe cases.

Diagnosis:

History Intermittent or constant → intermittent generally physiologic and related to some

sort of trigger (medication, activity) while constant is more worrisome for underlying pathology

Rest or action Action → postural (holding a particular position), isometric (exerting a

force), kinetic (movement) Rest → only at rest and may even diminish with action

Amplitude (“fast and fine”) → slow, medium, fast Severity of tremor does not correspond to severity of underlying cause

Types 1. Physiologic

Fine tremor Excitement or nervousness, Medication-/substance (caffeine) related that activate the sympathetic

system No further work-up necessary

2. Essential Very common 95% are kinetic (get worse when in action like reaching for a cup of coffee) Starts in the hands and wrists but can slowly progress over decades to

include the head, voice and lower extremities Often find relief in tremor with alcohol Medium rate and coarse (you can easily see on exam) tremor 50% are autosomal dominant, so patients will have a family history of

tremor (helpful to distinguish from Parkinson’s) 30-50% will develop some kind of movement disorder

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Can be debilitating forcing people into early retirement and causing them to avoid social situations

Spiral circle test: If big and shaky spiral more consistent with essential tremor If small and quivery more consistent with parkinsonian tremor

3. Parkinsonian Rest (none of the other tremors are present only at rest) NOT synonymous with Parkinson’s disease Slow and coarse tremor Antipsychotics, metoclopramide are common meds that can cause

4. Drug and metabolic Sympathomimetics: decongestants, methamphetamines SSRI’s Atorvastatin Steroids Levothyroxine Metabolic causes: hepatic encephalopathy, hypocalcemia, hypoglycemia,

hyperthyroidism, hyperparathyroidism, hypomagnesemia, B12 deficiency, uremia, heavy metal toxicity, pheochromocytoma

5. Cerebellar Red flag because causes are bad: MS, stroke, brain tumors Low frequency, low intention-type tremors Disabling Physical exam maneuvers:

Finger-to-nose test is abnormal = dysmetria Heel-to-shin is abnormal = dyssynergia Hypotonia

Image the brain if you suspect cerebellar tremor Treatment of essential tremor (the other categories warrant their own separate podcasts!):

No cure and slowly progressive PT/OT to help with tools/utensils that can be used at home Moderate alcohol does help (assuming person does not struggle with alcohol use disorder) Meds (short-acting for intermittent use and long-acting versions available):

1. Propranolol (non-selective beta-blocker) 2. Primidone 3. Topiramate

Deep brain stimulation or unilateral thalamotomy seem to help in severe cases Reference: Crawford P, Zimmerman EE, et al. Tremor: Sorting through the differential diagnosis. Am Fam Physician 2018; 97(3):180-186. Elias WJ, Shah BB. Tremor. JAMA. 2014;311(9):948-54 Pipas M, Dihabadi M, et al. Tremor. BMJ 2013; 347:f7200 Louis ED. Clinical Practice: Essential Tremor. N Engl J Med 2001; 345:887-891.

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Observation Care Steve Biederman MD, Tom Robertson MD Pearls:

Observation care is a billing designation that shifts inpatient care from Medicare Part A (inpatient services) to Medicare Part B (outpatient services) in an effort to decrease costs while not impacting quality.

Other than providing guidance that observation care falls within two midnights, CMS does little more to define who should be providing the care and what is included in that care.

Overall, data suggests it is both financially beneficial to the health system and non-inferior clinically; however, it seems poor patients end up paying more due to impaired access to care.

History of observation care (“obs”) designation: billing designation for patients being treated in the

hospital Medicare Part A covers inpatient, skilled nursing facility and hospice Medicare Part B covers outpatient services like primary care visits and preventive health Observation care was created to bill under Part B, instead of Part A for inpatient services CMS (Centers for Medicare & Medicaid Services) defined in 2006 as “ well-defined set of

specific clinically appropriate services which include ongoing short-term treatment, assessment, and reassessment that are furnished while a decision is being made regarding whether patients will require further treatment as hospital in-patients, or if they are able to be discharged from the hospital. ” Generally this observation period happens within a 48 hour window.

Real world practice differs significantly with a wide variety of diagnoses and times of observation.

CMS attempted to clarify in 2013 with the two midnight rule: if you think a patient will require less than two midnights, classify them as observation care. Is not based on diagnosis of level of care (ie: general floor v. ICU).

Observation care designation today: No specific guidance on location (ED, observation unit, floor unit) Anyone can be the provider (80% staffed by FM or IM doctors) No guidance on what type of services

Initial data around observation units was very protocol-driven CANNOT qualify for skilled nursing facility

Observation units: Started in ED’s as a place to observe low acuity patients while awaiting a decision to admit

or not Have been shown to decrease healthcare utilization without impacting quality Now patients can be admitted under the “obs” status anywhere in the hospital

Impact on costs: Decreased inpatient billing services while increasing outpatient billing Under Medicare A, if admitted to the hospital the patient has a one-time deductible of

$1340 that would also cover readmission.

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Under Medicare B where observation status lives, the patient pays a deductible every time. Medicare pays 80% while the patient pays 20% every time. Often times 20% of the services rendered is less than the $1340 deductible and will be capped at that amount if you were to exceed it in services.

Based on study in 2015, overall majority of patients pay $950 instead of $1340. However, a quarter of patients who tend to be poorer actually end up with larger financial liability because poorer access to care leads to frequent presentations to emergency departments.

Impact on clinical care: No randomized control trials but observational studies have consistently shown

non-inferiority in protocol-driven units and lower healthcare utilization

Reference: The World Bank. Health Expenditure, total (% of GDP) World Health Organization Global Health Expenditure Database. Accessed at https://data.worldbank.org/indicator/SH.XPD.TOTL.ZS/ Asudani, Deepak, et al. Pros and Cons of Clinical Observation Units. The Hospitalist. November 2013. https://www.the-hospitalist.org/hospitalist/article/125555/pros-and-cons-clinical-observation-units. Accessed 1/3/2018 Sheehy, AM, et al. Hospitalized but Not Admitted: characteristics of patients with “observation status” at an academic center. JAMA Intern Med. 2013; 173(21):1991-1998. Doi:10.1001/jamainternmed.2013.8185 Baugh, CW, et al. Making greater use of dedicated hospital observation units for many short-stay patients could save $3.1 billion a year. Health Aff (Millwood). 2012;31(10):2314-2323 Span, P. Under ‘Observation,’ Some Hospital Patients Face Big Bills. New York Times. Sept. 1,2017. Available at https://www.nytimes.com/2017/09/01/health/medicare-observation-hospitals.html Pub. L. 114-42. The NOTICE Act was signed by President Obama on August 6, 2015. SeeCenter for Medicare Advocacy, “Observation Status: The NOTICE Act Will Soon Be Law,” (CMA Alert, Aug. 6, 2015)Ross, Michael, et al. State of the Art: Emergency Department Observation Units. Critical Pathways in Cardiology 2012; https://insights.ovid.com/pubmed?pmid=22825533 National Committee to Preserve Social Security & Medicare, Fast Facts About Medicare. February 2017, available at http://www.ncpssm.org/Medicare/MedicareFastFacts Department of Health and Human Services and Centers for Medicare & Medicaid Services. Medicare benefit policy manual: chapter 6—hospital service covered under Part B. www.cms.gov/Regulations-and-guidance/Guidance/Transmittals/downloads/R42BP.pdf. Accessed January 1, 2018 Tang, N, et al. Trends and characteristics of US emergency department visits, 1997-2007. JAMA2010;3024:664-70 Cubanski, Juliette and Neuman, Tricia. The Facts on Medicare Spending and Financing. Kaiser Family Foundation, July 2017. https://www.kff.org/medicare/issue-brief/the-facts-on-medicare-spending-and-financing/

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Department of Health and Human Services and Centers for Medicare & Medicaid Services. Medicare benefit policy manual: chapter 6—hospital service covered under Part B. www.cms.gov/Regulations-and-guidance/Guidance/Transmittals/downloads/R42BP.pdf. Accessed January 1, 2018 Centers for Medicare & Medicaid Services. Fact Sheet: Two-Midnight Rule. https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheets-items/2015-07-01-2.html MedPac Report to the Congress: Medicare Payment Policy. Chapter 3: Hospital Inpatient and Outpatient Services. March 2017. www.medpac.gov/docs/default-source/reports/mar17_medpac_ch3.pdf?sfvrsn=0 Society of Hospital Medicine. The Hospital Observation Care Problem. November 2017, accessed at https://www.hospitalmedicine.org/policy--advocacy/current-issues/observation-status/ Ross, Michael, et al. Protocol-Driven Emergency Department Observation Units Offer Savings, Shorter Stays, and Reduced Admissions. Health AffairsDecember 2013. Baugh, Christopher, et al. Observation Care – High Value Care or a Cost-Shifting Loophole? New England Journal of Medicine, 2013; 369:302-305July 25, 2013DOI: 10.1056/NEJMp1304493 Kangovi S, Cafardi SG, Smith RA, Kulkarni R, Grande D, Patient Costs for Observation Care/. J. Hosp. Med 2015;11;718-723. doi:10.1002/jhm.2436 Goldstein, Jennifer, et al. Observation Status, Poverty, and High Financial Liability Among Medicare Beneficiaries. The American Journal of Medicine, Volume 131, Issue 1, 2018, Pages 101.e9-101.e15, ISSN 0002-9343 Office of Inspector General. Hospitals’ Use of Observation Stays and Short Inpatient Stays for Medicare Beneficiaries. July 2013. Accessed at https://oig.hhs.gov/oei/reports/oei-02-12-00040.asp Farkouh, Michael, et al. A Clinical Trial of a Chest-Pain Observation Unit for Patients with Unstable Angina. New England Journal of Medicine. 1998; 339:1882-1888, December 24, 1998. DOI: 10.1056/NEJM199812243392603 Goodacre S, Nicholl J, Dixon S, Cross E, Angelini K, Arnold J al. Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care. BMJ 2004; 328:254. Decker WW, Smars PA, Medano P, et al. A prospective randomized trial of an emergency department observation unit for acute onset atrial fibrillation. Ann Emerg Med. 2008;52:322–8. Rydman RJ, Isola ML, Roberts RR, et al. Emergency department observation unit versus hospital inpatient care for a chronic asthmatic population: a randomized trial of health status outcome and cost. Med Care. 1998;36:599–609. Stead, L.G., Bellolio, M.F., Suravaram, S. et al. Neurocrit Care (2009) 10: 204. https://doi.org/10.1007/s12028-008-9146-z Fadi Nahab, George Leach, Carlene Kingston, Osman Mir, Jerome Abramson, Sarah Hilton, Matthew Keadey, Bryce Gartland, Michael Ross, Impact of an Emergency Department Observation Unit Transient Ischemic

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Attack Protocol on Length of Stay and Cost, Journal of Stroke and Cerebrovascular Diseases, Volume 21, Issue 8, 2012, Pages 673-678, ISSN 1052-3057, https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.02.017.

Sickle Cell Emergencies Mizuho Morrison DO & Katie Harter MD, Jess Osterman MD

Pearls:

Be mindful of the high risk of infection, vaso-occlusion and end-organ complications in sickle cell patients and have a very low threshold for early initiation of intravenous analgesia and referral onto the emergency department.

BACKGROUND One in every 5,000 Americans have sickle cell disease and obviously it's more prominent in

African American population with about one in 365-500 African American children It's also quite prominent in the Hispanic community as well with about one in 36,000

Hispanic children having sickle cell. Sickle cell disease is an abnormality with hemoglobin S, an abnormal hemoglobin molecule

in the red blood cells. As hemoglobin S changes temperature or becomes dehydrated, it's actually going to become sickled, which causes it to be more rigid, lose its elasticity and burst within the blood vessels.

These patients have a hemoglobin anywhere between five to nine, a white blood cell count that tends to be higher than average (anywhere from 12 to 20,000) and thrombocytosis.

VASO-OCCLUSIVE OR PAIN CRISIS

Is caused by changes in altitude, temperature, dehydration or stress that causes red blood cells to sickle in the peripheral vessels resulting in ischemia and pain to especially distal areas of your body, fingers, toes

Up to 25% of vaso-occlusive crises can be precipitated by infection, which really underlines the importance of looking for a fever or any other signs of occult infection.

Vaso-occlusion can lead to significant end organ damage, including liver and kidney damage and even pulmonary embolism.

The goal in treating a pain crisis is to restore the patient back to a normal state of hydration (only if they are dehydrated) a normal state of oxygenation (only if they are hypoxemic) and to relieve their pain.

Do not shy away from oral opioids in this patient population. Keep in mind that IM opiods are less than an ideal in sickle cell patients because they have poor bioavailability and IM medications can very often can lead to some fairly significant complications, like avascular necrosis, abscess formation and granulomas at the injection site.

If the patient requires intravenous analgesia it should prompt referral to the emergency department.

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HEMOLYTIC CRISIS

Vaso-occlusive crisis and hemolytic crisis have similar triggers: They'll be dehydrated, have changes in altitude, stress, which causes an acute drop in their hemoglobin resulting in symptoms consistent with anemia.

This is a hemolytic process so they may present jaundiced. They may complain of weakness, lightheadedness, or presyncope.

APLASTIC CRISIS

Is caused by Parvovirus in sickle cell patients and completely prevents red blood cell production in the bone marrow for two to three days.

These patients will look ill appearing because they drop their hemoglobin and then can't make any new red blood cells.

Most Urgent Care centers will not have a reticulocyte count that they can do point of care so its best to refer any of these patients, especially if they have symptoms of a “slapped cheek” rash, to the ER immediately.

SEQUESTRATION CRISIS

Occurs when sickling blood cells cut off blood supply to splenic vessels. It's causes an acute, painful enlargement of the spleen and is associated with a precipitous

drop in hemoglobin. Sequestration tends to happen in younger kids because by the time they reach their

mid-teens and adulthood they've usually already infarcted their spleen to the point where they are functionally asplenic.

If any sickle cell patient is having significant pain in that left upper quadrant, you feel a tender big spleen, you must get them to the emergency department as fast as you can.

ACUTE CHEST SYNDROME

Is a vaso-occlusive pain crisis except localized to the lungs itself. The definition of acute chest is any two of the following: chest pain, fevers, a pulmonary

infiltrate or a focal abnormality on chest x ray, respiratory symptoms or hypoxia. Roughly a third of cases are from pneumonia, another third from pulmonary infarction and

the last third pulmonary embolism. Acute chest syndrome is one of the most common causes of death in patients with sickle

cell disease and should be high on the differential for any sickle cell patient with respiratory or chest symptoms.

These patients need immediate transfer to the ED STROKES

Strokes are most commonly seen in children with sickle cell disease due to an interruption of the cerebral vasculature by sickling cells.

It can present with a simple headache, focal weakness, dysarthria or loss of balance. These patients must be sent to the ER as fast as possible for really an exchange transfusion

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ACE vs ARB Andrew Buelt DO Pearls:

Latest data suggests ACE and ARB are equally effective in reducing cardiovascular mortality in those with hypertension, while ARB’s have lower risk of side effects like angioedema and cough.

ARBs can be safely used in patients who have had angioedema in reaction to ACE.

The ugly side of an ACE:

Angioedema: incidence is low of 0.1 percent with number needed to harm of 1 in 1000 or 1 in 5000) but three times higher in African Americans

Due to an increase in the bradykinin levels A second episode can happen about 1-2 weeks after drug is stopped because the

bradykinin levels are still elevated Are ARBs an alternative and can you just start with an ARB instead of an ACE: YES!

Meta-analysis from 2012 showed that rates of angioedema with ARB use were no different than placebo

Both are cheap The CONSENSUS trial (1987), SOLVD trial (1991) and SAVE trial (1992) demonstrate

benefit of ACE in reducing mortality and hospitalization in patients with heart failure reduced ejection fraction. The HOPE trial (2000) showed same results in heart failure with preserved ejection fraction.

Latest article in 2018 in Journal of American College of Cardiology compared ACE and ARB across 119 RCTs and found they were equally effective.

Reference:

OCTAVE trial. Am J Hypertens. 2004;17(2):103. https://www.ncbi.nlm.nih.gov/pubmed/14751650 Plasma bradykinin in angio-oedema. Lancet. 1998;351(9117):1693. https://www.ncbi.nlm.nih.gov/pubmed/9734886 Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. Am J Cardiol. 2012 Aug;110(3):383-91. Epub 2012 Apr 20. https://www.ncbi.nlm.nih.gov/pubmed/22521308 Yusuf S, et al. "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients". The New England Journal of Medicine . 2000. 342(3):145-153. https://www.nejm.org/doi/full/10.1056/nejm200001203420301 CONSENSUS (1987) SOLVD (1991) SAVE (1992)

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Franz H. Messerli et. al. Journal of the American College of Cardiology Apr 2018, 71 (13) 1474-1482. http://www.onlinejacc.org/content/71/13/1474

Paper Chase #1 - Diclofenac use and cardiovascular risks: series of nationwide cohort studies Matthew DeLaney MD and Matthieu DeClerck MD Schmidt M et. al. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018 Sep 4;362:k3426. PMID: 30181258 . Pearls:

Diclofenac has more cardiac and GI events compared to NSAIDs but when compared to paracetamol the risk of cardiac death is the same.

Danish nationwide cohort study with over a million people comparing diclofenac with

other NSAIDS like naproxen and ibuprofen as well as acetaminophen / paracetamol and the risk of cardiovascular events.

Diclofenac is a COX-1 and COX-2 inhibitor. The initial selective COX-2 inhibition was thought to increase cardiovascular events.

They looked at major adverse cardiac events and GI bleeding that started within 30 days of the first dose of the medication

Diclofenac use was associated with increased cardiovascular events (afib/flutter, ischemic stroke, heart failure, MI, cardiac death) and GI bleed compared to all other groups.

Interestingly paracetamol/acetaminophen had similar rates of cardiac death. Bottomline : Diclofenac has more cardiac and GI events compared to NSAIDs but when

compared to paracetamol the risk of cardiac death is the same.

Paper Chase #2 - Screening for cervical cancer: USPSTF recommendation statement Matthew DeLaney MD and Matthieu DeClerck MD US Preventive Services Task Force. Screening for Cervical Cancer. US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674–686. doi:10.1001/jama.2018.10897 . Pearls:

Updated recommendations for cervical cancer screening - see below.

Updated recommendations by age: Age 0-21 : no testing for cervical cancer because high false positive rates and most

clear the HPV virus Age 21-20 : cervical cytology every 3 years WITHOUT high-risk HPV testing

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Age 30-65: cytology alone every 3 years OR cytology + high-risk testing every 5 years

Bottomline : Updated recommendations for cervical cancer screening.

Paper Chase #3 - Two Articles on Aspirin Use and Cardiovascular Disease Prevention Matthew DeLaney MD and Matthieu DeClerck MD Gaziano JM et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double-blind, placebo-controlled trial. Lancet 2018 Aug 26; [e-pub] . The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018 Aug 26; [e-pub] . Pearls:

Two large trials showed daily aspirin 100mg did not change incidence of cardiovascular events like MI or stroke but did lower incidence by 1% in diabetic patients while raising risk of GI bleed by 1%.

Both studies look at the role of low dose aspirin in primary cardiovascular disease

prevention. The ARRIVE and ASCENT trial both took patients aged greater than 55 (or 60 for women)

who had average cardiovascular risk and randomized them to aspirin 100mg or placebo daily. ASCENT focused on patients with diabetes. More than 12,000 patients followed over 5 years.

Incidence in both groups of non-diabetic patients of MI and stroke was about 4%. Incidence of GI bleed in the aspirin group was 1% v. 0.5% in placebo group.

For diabetic patients, there was a 1% reduction in adverse cardiac events and 1% increase in the risk of GI bleed.

Rates of colorectal cancer were about the same; however, the study probably wasn’t long enough to see a difference in cancer incidence.

Bottomline : Two large trials showed daily aspirin 100mg did not change incidence of cardiovascular events like MI or stroke but did lower incidence by 1% in diabetic patients while raising risk of GI bleed by 1%.

Paper Chase #4 - Risks/benefits of direct oral anticoagulants versus warfarin Matthew DeLaney MD and Matthieu DeClerck MD Vinogradova et. al. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ 2018; 362 :k2505 .

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Pearls: Overall, apixaban was found to be the safest drug, with reduced risks of major,

intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were associated with increased risks of all cause mortality compared with warfarin.

Large study of UK primary care data set comparing direct oral anticoagulants (rivaroxaban,

dabigatran and apixaban) and warfarin in terms of bleeding risk and all-cause mortality. Apixaban was the safest drug. Both rivaroxaban and dabigatran had lower bleeding risk than warfarin. Rivaroxaban and lose dose apixaban were associated with increased risk of all-cause

mortality compared to warfarin. Low dose apixaban 2.5mg twice daily is reserved for those patients who are over

80, cachectic (<60kg) or have a Cr > 1.5 → probably sicker patients overall Bottomline : Overall, apixaban was found to be the safest drug, with reduced risks of major,

intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were associated with increased risks of all cause mortality compared with warfarin.

Paper Chase #5 - Anticonvulsants in the treatment of low back pain Matthew DeLaney MD and Matthieu DeClerck MD Enke O et. al. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ. 2018 Jul 3;190(26):E786-E793. PMID: 29970367 . Pearls:

Large meta-analysis did not provide evidence in support of gabapentin and pregabalin. Maybe some benefit from topiramate.

Meta-analysis delving into the effectiveness of gabapentin, pregabalin and topiramate for

lower back pain and lumbar radicular pain. Gabapentin and pregabalin don’t really work for lower back pain with or without sciatica

and were more likely to harm (increase risk of suicidality, misuse, drowsiness, nausea, dizziness).

Topiramate may have some benefit. Bottomline : There is moderate- to high-quality evidence that anticonvulsants are

ineffective for treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids have a higher risk for adverse events.

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