Primary Care RAP April 2018 Written Summary - Changi General ...
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Primary Care RAP April 2018 Written Summary
Editor-in-Chief: Neda Frayha MD
Associate Editor: Kenji Taylor MD, MSc
Intro - Social Media
Heidi James MD, Neda Frayha MD
Pearls:
● Social media has both benefits and downsides. There are guidelines that help provide
some framework for interacting with patients on social media as well as reaping the
benefits of active social media use.
● One reader asked about the Boston Lipid Panel. It is a panel of HDL subtypes of unclear
clinical significance. The test was produced by Boston Heart Diagnostics, which was
being investigated for physician kickbacks just prior to its sale to Eurofin in 2014.
● Social media as physicians: Heidi and Neda discuss the pitfalls, perils and guidelines
around the use of social media as physicians.
○ 80% of physicians use the Internet on a daily basis and of those 90% use social
media in some form or another
● Guidelines:
○ 2017 Federation of State and Medical Boards (FSMB)
■ Discourage interacting with current or past patients on personal social
networking sites like Facebook.
■ Physicians should only have online interaction with patients when
discussing the patient’s medical treatment within the patient/physician
relationship.
● These interactions should never occur on personal social
networking sites.
○ Other guidelines from the Canadian Medical Association, the American Medical
Association (AMA) and the American College of Physicians (ACP) are largely in line
with these guidelines.
■ They also comment on the importance of protecting patient privacy.
■ Discuss importance for physicians to monitor and audit our own online
presence to make sure what is out there is accurate and professional.
○ The American Academy of Family Physicians (AAFP)
Primary Care RAP April 2018 Written Summary | hippoed.com/pc■ Discusses benefits of social media engagement, disseminating medical
knowledge, improving professional networking to stay current within one’s
specialty
● Listener Question: Greetings, I am a family practitioner who is a huge fan of your podcast. I love
the end of the month because I know there will be a new Primary Care RAP podcast. I was hoping
there could be some discussion regarding the Boston Lipid Panel.
○ The Boston Lipid Panel is a lab test from Boston Heart Diagnostics that measures
five HDL subtypes - pre-beta 1, alpha 4, alpha 3, alpha 2 and alpha 1. They claim the
more detailed breakdown more accurately assesses cardiovascular risk as opposed
to the standard HDL assays.
○ What is the evidence?
■ Prospective study of Finnish men in Circulation 1991 showed an inverse
association between total HDL and HDL 2 levels with the risk of MI.
● Salonen JT et. al. HDL, HDL2, and HDL3 subfractions, and the risk of
acute myocardial infarction. A prospective population study in eastern
Finnish men. Circulation. 1991 Jul;84(1):129-39. PMID: 2060089.
■ Prospective study of Japanese adults in Stroke 2013 found that small to
medium-size HDL subtypes were associated with an inverse risk of stroke.
● Chei CL et. al. High-density lipoprotein subclasses and risk of stroke and
its subtypes in Japanese population: the Circulatory Risk in Communities
Study. Stroke. 2013 Feb;44(2):327-33. PMID: 23321451.
○ A Boston Globe Article from 2014 discussed how the company was under
investigation for improperly providing kickback payments to physicians who used
the tests and was then bought by Eurofins Diagnostics.
○ Bottomline: Not a recommended test.
Lifestyle and Diabetes - Part 2
Heidi James MD, Neil Skolnik, MD
Pearls:
● Diet and exercise both have beneficial effects in DM control by increasing insulin
sensitivity through weight loss.
● Evidence strongly supports the role of diet and exercise in progression of diabetes and
also has positive effects on reduced A1c, reduced cholesterol levels and less medications
to control blood pressure in those who have diabetes.
● Work with patients to develop a specific and concrete plan of lifestyle modifications
where you serve as the coach along the way with the patient leading.
● Recap of Part 1: we reviewed the Diabetes Prevention Program (DPP) that demonstrated
how lifestyle modification prevented progression to diabetes 58% of the time compared to
30% of the group taking metformin 850mg twice a day.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 2● How do diet and exercise work to help control diabetes?
○ Diet: obesity → insulin resistance → beta cell senescence
○ Exercise:
■ 1. Improves insulin sensitivity. The effect is rapid: short bursts of activity
(ie: 20-30 minutes getting up) while sedentary has immediate effects on
increasing insulin sensitivity
■ 2. Causes weight loss
○ Cochrane review in 2007 showed 1.1kg increase in weight loss with diet and
exercise as opposed to just diet.
■ Franz MJ et. al. Weight-loss outcomes: a systematic review and meta-analysis of
weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc.
2007 Oct;107(10):1755-67. PMID: 17904936.
● Evidence supporting diet and exercise once someone has diabetes:
○ The LOOK Ahead Trial enrolled over 5000 people similar to the DPP trial of active
lifestyle modification.
■ It was stopped for futility after 9 years because the primary endpoint of
decrease in cardiovascular outcomes didn’t happen. However, the patients
were older and had higher A1c’s with a diagnosis of diabetes.
■ However, the group in the intervention arm had better A1c’s, better
cholesterol and needed less medication to control their blood pressure.
■ Also the intervention group with arthritis had better mobility and much less
pain.
■ Bottomline: Encourage patients with diabetes to exercise and change their
diet because it does have many positive effects. And really focus on those
with prediabetes to reverse the course of their disease.
■ Look AHEAD Research Group et. al. Cardiovascular effects of intensive
lifestyle intervention in type 2 diabetes. N Engl J Med. 2013 Jul
■ 11;369(2):145-54. PMID: 23796131.
● Developing a plan (exercise and diet) for patients:
○ Get a commitment to change and meet patients where they are: “What would you
like to do about your diabetes?”
○ Develop a concrete plan: exercise type, how to do the exercise, duration, markers
of success to set a person up for success (ie: commitment to regularly exercising
preferred over biophysical markers like weight loss)
■ Evidence suggests the health outcomes of exercise come from the behavior
itself and not the actual weight loss
○ See patients back frequently if it helpful for them to have a coach along the way
■ Example schedule: every 6 weeks for 4 visits, every 3 months for 2 years
and then every 6 months
○ Recognize how hard it is for patients to make these changes and help encourage
them to success
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 3TIDBSI: UTI
Vanessa Cardy MD, Adrien Selim MD
Pearls:
● In a woman with classic symptoms of an uncomplicated UTI, you can just treat on
symptoms alone even in the face of a negative UA because the likelihood of UTI is 96%.
● If the symptoms are not classic, send a urine off in this case and consider UTI mimics
(STI’s, vulvar/vaginal pathology, bladder pain syndrome and other urologic problems).
● Have a low threshold for STI testing in young adolescent patients, including testing for
trichomonas, because no symptom constellation or urinalysis findings reliably predict
STI vs. UTI.
● Do we treat a young healthy woman with (uncomplicated) UTI symptoms but a negative
dip?
○ Urine dipstick:
■ Leukocyte esterase looks at chemical reaction from an enzyme present on
neutrophils
■ Nitrites look at chemical conversion of nitrates to nitrites that occur from
bacteria in enterobacteriaceae species like E. Coli. Pseudomonas and
enterococcus cannot perform this reaction.
■ If you consider a test “positive” with either nitrites or leukocyte esterase
positivity, sensitivity is 75% and specificity 80% for UTI.
○ Article in JAMA looked specifically at this issue:
■ A woman with typical symptoms (acute onset dysuria, frequency, urgency
and no vaginal discharge) has a 96% likelihood of having cystitis.
■ They suggest the likelihood is so high you don’t need a urine dipstick
■ If the woman has only dysuria but not other symptoms, then the likelihood
of cystitis is much lower, then they recommend a urine dip.
● If the urine dip is positive for either white blood cells or nitrites then
the probability of UTI is around 80%. You may just treat empirically.
● If the urine dip is negative, then the probability is around 20%. You
may send for culture and treat based on those results. You may also
need to start considering other diagnoses.
■ Bent S. Does this woman have an acute uncomplicated urinary tract infection?
JAMA. 2002 May 22-29. PMID: 12020306.
○ UTI mimics:
■ 1. Sexually transmitted infections:
● More common in younger women and those with new or multiple
sex partners
● Depending on the population (ie: young, urban), STI incidence may
be anywhere from 10-33%. The most common organisms are
trichomonas, chlamydia and gonorrhea.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 4● Studies found no good symptoms or urinalysis characteristics that
reliably predict UTI or STI.
○ Tomas ME et. al. Overdiagnosis of Urinary Tract Infection and
Underdiagnosis of Sexually Transmitted Infection in Adult
Women Presenting to an Emergency Department. J Clin
Microbiol. 2015 Aug;53(8):2686-92. PMID: 26063863.
○ Huppert JS et. al. Urinary symptoms in adolescent females: STI or
UTI? J Adolesc Health. 2007 May;40(5):418-24. PMID:
17448399.
■ 2. Vulvar and vaginal pathology:
● Candida - white cottage cheese discharge, vaginal irritation,
pruritus and external dysuria.
● Atrophic - postmenopausal thinning of the vulva vaginal skin that
may lead to erosions and external dysuria if the skin is irritated.
Treated with topical estrogens.
● Irritant - contact dermatitis to fragrances, skin products,
spermicides, latex, creams, detergents. Avoid the offending agent
and treat with topical corticosteroid
■ 3. Bladder pain syndrome (ie: Interstitial cystitis) - unpleasant sensations of
pain/pressure/discomfort associated with the urinary bladder and also with
lower urinary tract symptoms of more than 6 weeks duration in the
absence of infection or other identifiable causes. Dyspareunia also
common.
● More than 90% affected are women
● Related to IBS and fibromyalgia
● You may diagnose based on symptoms alone or more likely refer to
urology for additional diagnostics.
● Treatment includes avoidance of triggers like citrus and caffeine,
stress reduction, pelvic floor exercises and physical therapy.
■ 4. Urological problems: bladder cancer (hematuria common),
nephrolithiasis when the stones are migrating down to the distal uterine
bladder and urethral diverticula (outpouchings into the surrounding tissue)
● Referral to urology or urogynecologist is a good idea
○ Bottomline:
■ In a woman with classic symptoms of an uncomplicated UTI, you can just
treat on symptoms alone even in the face of a negative UA because the
likelihood of UTI is 96%.
■ If the symptoms are not classic, send a urine off in this case and consider
UTI mimics (STI’s, vulvar/vaginal pathology, bladder pain syndrome and
other urologic problems).
■ Have a low threshold for STI testing in young adolescent patients, including
testing for trichomonas, because no symptom constellation or urinalysis
findings reliably predict STI vs. UTI.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 5Deprescribing in Elderly Patients - A follow-up to January 2018 PC-RAP
Neda Frayha MD, Nicole Brandt PharmD, MBA
Pearls:
● Deprescribing is the systematic process of evaluating the risks/benefits of medication to
determine whether or not a patient should continue taking it.
● There are many reasons to deprescribe medicines including: adverse events, cost,
drug-drug interactions and changing treatment targets as patients age.
● A systematic approach to deprescribing includes getting a comprehensive medical
reconciliation, assessing the long-term goals for a patient versus the risk/benefit of their
medications and then putting together a monitoring plan to discontinue the medication.
● Some resources to help deprescribe include: BEERS list, STOPP/START criteria,
medstopper.com, and deprescribing.org.
● Deprescribing: the systematic process of evaluating the risks/benefits of a medication to
determine whether or not a patient should continue taking it.
○ Pearl: it’s all about patient-centeredness - i.e., what is the goal of their care? what is
the prognosis? where are they in their treatment algorithm?
● Why deprescribe?
○ Adverse events (falls, delirium) are even more problematic with elderly patients.
The risk of adverse events increases as the medications increase.
○ Patients on a fixed income often struggle with the cost of medications. The more
we can relieve that financial burden, the better.
○ The potential for drug-drug interactions increases as medication burden increases.
○ Treatment targets often change with age, so deprescribing gives us the opportunity
to re-evaluate those goals.
● What are the challenges to deprescribing?
○ Time, time, time!
○ Prescriber attitudes - “I didn’t start it so I’m not going to stop it.”
○ Patient attitudes - some may wonder if their goals of care are changing or if the
provider has given up on them. Patients also generally expect more prescriptions
rather than prescriptions being taken away at a visit.
○ Public media - providers are under stress to follow guidelines (i.e., statins,
ACE-inhibitors, etc.) that may not really pertain to an individual patient.
○ Peers - also influence of those you work with on reviewing your prescribing habits
and how it fits into the broader group practice.
● What is a systematic approach to deprescribing?
○ 1. Get a comprehensive medical reconciliation
■ Consider engaging other staff to accomplish this task like students,
pharmacists, health coaches
○ 2. Assess patient goals along with the risks or benefits of the medications
○ 3. Put together a plan to stop medications where the risks outweigh the benefits
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 6■ What are your beliefs and feelings about stopping this medication?
■ Monitoring for adverse withdrawal symptoms (ie: opiates, PPIs, SSRIs)
○ 4. Let the pharmacy know when you have stopped a medication
● Once you’ve decided to stop a medication, there are tools to help figure out if you can
figure out how to taper it.
○ MedStopper.com can help determine which meds to expect withdrawal
○ General rule: If there is physical or psychological dependence, consider a longer
taper
○ BEERS criteria for looking at higher risk medications in the geriatric population
■ Published by the American Geriatric Society
■ List of potentially inappropriate medications, those that need to be renally
dosed and clinically significant drug-drug interactions
■ Updated every 3 years with a review of the literature
○ STOPP/START
■ List of medications to deprescribe (STOPP) and medications that are often
under-prescribed (START) like anticoagulation or bone-active for
osteoporosis
● Other resources to stay up-to-date?
○ Deprescribing.org: website put out by the Canadian Network that focused on
provider education and high-risk drugs like antipsychotics, benzodiazepines,
proton-pump inhibitors.
Suboxone
Adrien Selim MD, Eric Contant MD
Pearls:
● Suboxone is a combination of buprenorphine (a partial mu opioid agonist) and naloxone
(an opioid antagonist) used for the long-term treatment of opioid use disorder.
● Upsides of suboxone: safer profile than methadone (basically no risk of overdose, no QT
prolongation), less close follow-up required and can be prescribed in the primary care
setting, ideal in rural setting where there is no methadone clinic, less cognitive side
effects if needed for someone who is working, safe in pregnancy.
● Downsides of suboxone: more experience with methadone, some patients will benefit
more from the daily structure of methadone.
● Suboxone induction requires the patient be in mild withdrawal in order to titrate the
medication. See below for details.
● Opioids can be prescribed to someone on suboxone; however, it may require using
opioid alternatives, using short-acting opioids or temporarily stopping the suboxone
● Suboxone:
○ Combination of buprenorphine and naloxone in a 4:1 ratio
■ Naloxone is an opioid antagonist
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 7■ Buprenorphine is partial mu opioid agonist with high binding affinity for the
receptors but low intrinsic activity
● Once stuck on the receptor it stays there and is so powerful that it
kicks the other agonists off → therefore it may precipitate
withdrawal
● Low intrinsic activity means it has a ceiling effect where increases in
dosage do not lead to increased side effects (ie: respiratory
depression)
○ Long half-life + low intrinsic effect =
■ Not much euphoria or any sedative effect, lower risk of overdose
■ Relieves withdrawal and cravings for more than 24 hours
● How/why are buprenorphine and naloxone combined?
○ 4 parts buprenorphine and 1 part naloxone
○ Naloxone is poorly absorbed sublingually and basically has little effect. However, if
suboxone is injected, naloxone has a much greater effect and will precipitate
withdrawal as a deterrent to abuse.
● When starting suboxone, what are some of the side effects?
○ Typical opioid toxidrome: constipation, mild sedation, tiredness, headache
○ Precipitates withdrawal
○ Generally does not prolong QT like methadone
● Who would be the ideal candidate for suboxone treatment?
○ Anyone with an opioid use disorder
○ Control the risk of illicit drug use, reduce risk activities like needle sharing, increase
retention in the healthcare system, control withdrawal symptoms and also control
how quickly opioid tapering is done
● How does suboxone compare to methadone?
○ Suboxone: safer profile than methadone (basically no risk of overdose, no QT
prolongation), less close follow-up required and can be prescribed in the primary
care setting, ideal in rural setting where there is no methadone clinic, less cognitive
side effects if needed for someone who is working, safe in pregnancy
○ Methadone: mixed data on effectiveness for treatment of opioid dependence but
because it has been around longer providers are more comfortable with it, cheaper,
less risk of diverting, still firstline for pregnancy, more experience with the drug
● What is the training required to prescribe it?
○ Varies by jurisdiction but spans the spectrum of requiring an additional license to
no additional needed training
● How do you do a suboxone induction?
○ Should have a multidisciplinary physical and psychological assessment. Suboxone is
only one piece of treating addiction.
○ 1. The patient should be in moderate withdrawal (ie: generally 12 hours after a
short-acting opioid to 24 hours after a long-acting opioid), COWS score > 12.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 8■ COWS score (clinical opioid withdrawal score): points-based, systematic
and objective way of quantifying opioid withdrawal that includes features
such as rhinorrhea, piloerection, yawning, myalgias, nausea, pupil dilation
○ 2. Initial dose is 2-4 mg buprenorphine sublingual x 1.
○ 3. Recheck in one hour.
■ If worsening withdrawal, treat the withdrawal with clonidine and
antiemetics and have them return the next day.
■ If you don’t precipitate withdrawal →reassess in 3 hours and if still feeling
well, then stop there.
○ 4. If you don’t precipitate withdrawal after 3 hours but the patient still has
symptoms of mild withdrawal, have the patient take another 2-4mg. The maximum
daily dose during induction in 8mg on the first day. If still having withdrawal after 3
hours, treat the withdrawal symptomatically and have them return in one day.
○ 5. The following day, if still feeling alright you have your stable dose. If not, you can
add more buprenorphine by 2-4mg per day.
○ Usual doses are between 8-16mg, though the manufacturer maximum is 30mg (not
very often do you see doses that high).
○ Remember: the goal is relieve withdrawal and craving symptoms for 24 hours at
time.
● Considerations to talk to your patients about:
○ Do not co-ingest alcohol or any other sedatives
○ Do not drive or do any high risk activity during induction until a stable dose is
reached
● Now that your patient is on a stable dose, do they have to go and get the medication
daily while being observed taking it (DOT - direct observed therapy)?
○ It will depend on local context. There are no clear guidelines. It needs to be
determined on a case-by-case basis
■ Health Canada suggests all doses should be DOT for at least the first few
months, expect weekends on holidays.
■ The Ontario guideline says DOT is not based on evidence.
● What about urine drug testing?
○ Some sources recommend screening at every visit while others say to save it for
when clinically indicated.
○ Pearl: buprenorphine will not cause a positive screen on urine drug screen
○ Probably recommended doing it at least every couple of months
● What if you see a patient in the ED requesting a missed dose?
○ Generally defer treatment to the primary provider or subscriber and treat
symptoms with clonidine or antiemetics.
○ If last dose was within 5 days, going back to the prior dose is fine but if more than 5
days, the starting dose has to be lower depending on how many days they have
missed.
● What is the end point for suboxone?
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 9○ It is a long-term treatment with a good outcome being return to normal day-to-day
functioning and harm reduction. You could taper it and eventually stop it but it is
fine for patients to be on it long-term.
○ If a patient endorses side effects like constipation and sedation, you could consider
a taper:
■ Decrease the dose 2mg every couple of days
■ Slower tapers seem to be better than faster
■ There is a high risk of relapse
○ For a good read on tapering buprenorphine that found long-term maintenance was
more effective than tapering, click on the link below:
■ Fiellin DA et. al. Primary care-based buprenorphine taper vs maintenance
therapy for prescription opioid dependence: a randomized clinical trial. JAMA
Intern Med. 2014 Dec;174(12):1947-54. PMID: 25330017.
● What about a patient on suboxone who needs acute pain treatment (ie: kidney stone,
broken bone)?
○ Have an honest discussion with the patient that their pain will be more complicated
to manage because of the suboxone but that you will work on managing it.
○ Consider these options:
■ 1. Consider opioid alternatives: NSAIDS, acetaminophen, ketamine
(1mg/kg infused slowly over 20 minutes), regional blocks (i.e., broken arm)
■ 2. You can use short-acting opioids.
● Pearl: NO evidence to suggest this increases addiction relapse
● Tell the patient you are giving them opioids because it will show up
as a positive on their next urine drug screen if being done in the next
couple days or weeks
● You have to titrate the medication carefully because initially the
suboxone will counteract the effect of the medication and once it
wears off you are at increased risk of overdose
● Pearl: remember the ceiling effect of buprenorphine is low so it
rarely causes respiratory depression except if there is underlying
lung disease and more often some other sedative on-board.
■ 3. You can divide the regular suboxone dose into every 6-8 hours (i.e., if
they take 16mg daily, they could take 4mg every 4 hours)
■ 4. Stop the suboxone and switch to an opioid that you can titrate. The
downside is you’ll have to re-induce the patient on suboxone.
■ 5 . Give additional doses of suboxone during the painful episode.
■ 6. For sicker patients who may end up being admitted, switch them over to
methadone.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 10Contralateral Breast Mastectomies
Andrew Buelt DO and Jake Anderson MD
Pearls:
● Contralateral prophylactic breast mastectomies (CPM) are removal of the contralateral
breast after diagnosis and treatment of breast cancer in the other breast.
● CPM is becoming increasingly popular despite evidence that it does not reduce the risk
of recurrence in women who are not BRCA carriers or have some other high risk
personal/family history of breast cancer. However, CPM does decrease the risk of
recurrent breast cancer in those with BRCA mutation by at least 90%.
● Up to 20% of those who undergo CPM will experience an adverse event such as
hematoma, infection, contracture or implant rupture.
● The decision to undergo CPM is fraught with emotions and misinformation. Make sure
your patients are well-informed while respecting their personal preferences.
● Contralateral prophylactic breast mastectomies (CPM): surgery the woman chooses to
undergo on the healthy breast after having been diagnosed and treated with breast cancer
on the other breast.
● How common is CPM?
○ JAMA Surgery 2014 surveyed 1400 women and found:
■ 19% strongly considered CPM and 7.6% received it
■ 69% of those who received CPM had no major genetic or familial risk
factors for contralateral disease and 80% said it was done to prevent breast
cancer from developing in the other breast
■ Hawley ST, et. al. Social and Clinical Determinants of Contralateral Prophylactic
Mastectomy. JAMA Surg. 2014 Jun;149(6):582-9. PMID: 24849045.
● CPM vs. other treatments for all-comers:
○ Researchers evaluated 200,000 women diagnosed with stage 0 to stage 3 breast
cancer in CA from 1998-2011 to assess the association between mortality rates
and unilateral mastectomy, bilateral mastectomy and breast-conserving therapy
(i.e., lumpectomy) followed by radiation.
○ 189,000 patients were involved:
■ 55% underwent breast conserving therapy
■ 38.8% unilateral mastectomy (declined over the study period)
■ 6% bilateral mastectomy (increased over the study period, greatest
increase in women younger than 40 years old)
○ Outcomes: propensity analysis, estimated 10-year mortality rates
■ 20% for unilateral mastectomy
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 11■ 19% for bilateral mastectomy
■ 17% for breast conserving therapy + radiation
○ Bottomline: Breast conserving therapy with radiation did the best while unilateral
mastectomy did the worse.
■ One hypothesis why unilateral mastectomy did the worst is because it was
done in patients from lower socioeconomic status.
○ Kurian AW et. al. Use of and mortality after bilateral mastectomy compared with other
surgical treatments for breast cancer in California, 1998-2011. JAMA. 2014 Sep
3;312(9):902-14. PMID: 25182099.
● BRCA:
○ BRCA negative patients have a risk of contralateral breast cancer of 0.5-1% per
year
○ BRCA positive patients have a risk of contralateral breast cancer of 10-25% per
year. Some studies say it’s as high as 50-65%
● CPM for those with BRCA mutation:
○ PROSE Study looked at 483 people with BRCA1 and 2 mutation carriers and those
who underwent bilateral prophylactic mastectomy and controls without CPM or
breast cancer at the time of the matched subjects surgery.
■ Mean age of surgery 38
■ Of the 105 mutation carriers who underwent CPM, 2 (2%) were diagnosed
with subcutaneous cancer after the surgery (2.3 and 9.2 years after
surgery)
■ In the control group, 184 (49%) of 378 developed breast cancer
○ Bottomline: CPM reduced risk of breast cancer by about 90% in BRCA1 and 2
mutation carriers.
○ Rebbeck TR et. al. Bilateral prophylactic mastectomy reduces breast cancer risk in
BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004 Mar
15;22(6):1055-62. PMID: 14981104.
● What about the risk of CPM?
○ Study looked at 112 high risk women, 79 with BRCA mutation who underwent
CPM, 103 with immediate reconstruction → 21% had complications including
hematoma, infection, contracture or implant rupture.
○ Contant CM et. al. Clinical experience of prophylactic mastectomy followed by
immediate breast reconstruction in women at hereditary risk of breast cancer (HB(O)C)
or a proven BRCA1 and BRCA2 germ-line mutation. Eur J Surg Oncol. 2002
Sep;28(6):627-32. PMID: 12359199.
● Other factors that affect choice for CPM:
○ Desire to be done with procedures and “do it all at once”
○ Less follow-up and anxiety around surveillance imaging
■ Patients who underwent CPM reported significant impacts on their
self-esteem and sexuality with over 80% confident in their decision and
90% saying they would make the same decision.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 12● Frost MH et. al. Contralateral prophylactic mastectomy: long-term
consistency of satisfaction and adverse effects and the significance of
informed decision-making, quality of life, and personality traits. Ann Surg
Oncol. 2011 Oct;18(11):3110-6. PMID: 21947589.
○ Overestimation of risk at initial diagnosis and overestimation of benefit
■ Annals of Internal Medicine paper in 2013 found that of the 123 women
surveyed, 94% thought CPM would improve their chances of survival and
98% believed the additional surgery would reduce the risk that cancer
would develop in the other breast.
■ Rosenberg SM et. al. Perceptions, knowledge, and satisfaction with contralateral
prophylactic mastectomy among young women with breast cancer: a
cross-sectional survey. Ann Intern Med. 2013 Sep 17;159(6):373-81. PMID:
24042365.
○ Younger age
○ Caucasian
○ Family history of breast cancer
○ Access to private insurance
○ Noninvasive or lobular tumor histology
● Bottomline: Make sure your patients have all the information and take some time to really
consider the risks/benefits of the surgery as well as their own goals and preferences.
○ Rosenberg SM et. al. Contralateral Prophylactic Mastectomy: An Opportunity for Shared
Decision Making. JAMA Surg. 2014 Jun;149(6):589-90. PMID: 24848646.
Are You Sure It’s Cellulitis?
Greg Moran MD, Matt DeLaney MD & Mizuho Spangler DO
Pearls:
❏ Cephalexin alone is the treatment of choice for patients with uncomplicated,
non-purulent cellulitis
❏ Avoid the use of a one time dose IV/ IM antibiotics in the UC
COMMON PITFALLS
● Chronic venous stasis can be difficult to distinguish from cellulitis as it also causes pain,
edema, and dependent erythema
● Patients with chronic venous stasis and lymphedema are at increased risk for cellulitis and
superinfection
● Weng QY, et al. Costs and Consequences Associated With Misdiagnosed Lower Extremity
Cellulitis. JAMA Dermatol. 2016 [PMID: 27806170]
○ Of 259 patients admitted through the emergency department with a cellulitis, ⅓
were found by a panel of dermatologists to simply have an exacerbation of an
underlying skin condition
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 13● Consider an alternative diagnosis when evaluating a patient with what looks like
bilateral cellulitis as this is less likely to be secondary to infection
MAKING THE CORRECT DIAGNOSIS
● Determining the baseline appearance of the legs will help differentiate chronic stasis
dermatitis from a superimposed cellulitis
● Minor skin changes over a long period of time are less concerning cellulitis while rapid
involvement is more likely infectious
● Fever suggests infection, but absence of fever does not rule out cellulitis
● Consider DVT if high risk for thrombosis as DVT can also cause erythema and swelling
TREATMENT
● Cellulitis without abscess is most likely secondary to streptococcal infection
● Cephalexin monotherapy will cover both streptococcus and MSSA and is the treatment
of choice for outpatient management of uncomplicated cellulitis
● For cellulitis with abscess the addition of trimethoprim-sulfamethoxazole (Bactrim) is
recommended if there is concern for MRSA
● Moran GJ, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone
on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA.
2017;317(20):2088-2096 [PMID: 2 8535235]
○ In this multicenter, double-blind, randomized superiority trial of roughly 500
patients with uncomplicated cellulitis, the use of cephalexin plus
trimethoprim-sulfamethoxazole compared to cephalexin alone did not result in
higher rates of clinical resolution of cellulitis
● Give the first dose of oral antibiotic in the urgent care before discharging the patient
instead of a one time dose of IM or IV antibiotic
● There are no good clinical decision rules or clinical criteria to help risk-stratify patients
who can be treated safely as an outpatient compared to those that need admission to the
hospital
● Talan DA, et al. Factors associated with decision to hospitalize emergency department patients
with skin and soft tissue infection. West J Emerg Med. 2015;16(1):89-97 [PMID: 25671016]
○ Among roughly 600 patients who presented to the ER for skin and soft tissue
infections, 15% were admitted, ~40% of which were admitted only for IV
antibiotics
● Demarking the patient’s cellulitis with a pen along the outer edges will help the patient
track their progress and assist physician decision-making should the patient bounce back
to the hospital
● Patients should be given clear discharge instructions to return to the hospital should their
cellulitis progress
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 14Vitamin D - An Update!
Brandon Grove
Pearls:
● Vitamin D is a fat soluble vitamin that is synthesized in the skin, liver and then kidney.
● 25-hydroxyvitamin D is the main reservoir of Vitamin D in the body with a half-life of 2-3
weeks, making it the lab test we use to monitor levels.
● Recommended supplementation is:
○ Infants up to age 1: vitamin D3 400IUD daily
○ Children age 1 to adults age 70: vitamin D3 600IU daily
○ Over age 70: vitamin D3 800IU daily
● The most recent research has shown improvement in pain, autism symptoms, risk of
breast cancer but has not been shown to decrease risk of hip fracture in elderly patients.
● Vitamin D
○ Fat soluble vitamin (along with A, E, K)
○ Not found naturally in large quantities in staple foods (unless you likely fatty fish
livers)
○ The sun helps us synthesize vitamin D in the dermis, which makes activated
pre-vitamin D (aka cholecalciferol, a cholesterol derivative)
■ Pre-vitamin D3 gets shipped to the liver where it is hydroxylated to the 25
position on the cholesterol ring to then give us 25 hydroxyvitamin D (aka
ergocalciferol, the lab test we order)
■ 25-hydroxyvitamin D3 then gets shipped to the kidneys where it picks up
another hydroxylase at the 1 position, give us the most active form of
1,25-dihydroxyvitamin D (aka calcitriol, 100x more potent than
25-hydroxyvitamin D)
● Forms of Vitamin D
○ Pre-vitamin D3: half-life of 24-hours
○ 25-hydroxyvitamin D: half-life of 2-3 weeks, main reservoir in the body, best
marker for vitamin D levels in the body
○ 1,25-dihydroxyvitamin D: half-life 4-6 hours, most potent form but not a useful lab
marker
● Clinical Relevance: vitamin D and metabolites are important for calcium homeostasis and
bone health
○ Works in the cells lining the small intestine to increase calcium absorption
○ Aids in small intestine enterocyte cell line differentiation and phosphate
absorption by these cells
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 15○ Indirectly suppresses parathyroid hormone release on localized osteoblast and
osteoclast activity
○ If you are vitamin D deficient: decreased calcium absorption, secondary
hyperparathyroidism leading to dumping of calcium and phosphorous in the
kidney, demineralization and then osteoporosis
○ Who is vitamin D deficient?
○ National sample from 2005-2006 showed 41% of adults over 20 have
25-hydroxyvitamin D levels less than 20mg/dL.
○ The farther from the equator, the less sun and the more prevalent vitamin D
deficiency becomes
● Vitamin D supplementation?
○ Infants up to age 1: vitamin D3 400IUD daily
○ Children age 1 to adults age 70: vitamin D3 600IU daily
○ Over age 70: vitamin D3 800IU daily
● Who is at risk for deficiency?
○ 1. Absorption problems: celiac disease, short-gut syndrome, IBD, cystic fibrosis,
pancreatic insufficiency, cholestatic liver disease; chronic steroid use (impairs
vitamin D-dependent absorption of calcium)
○ 2. Impaired hydroxylation in the liver: chronic liver disease (impairment of
hepatocytes to do their job), chronic alcohol or tylenol ingestion, steatohepatitis
○ 3. Impaired hydroxylation in the kidneys: chronic kidney disease
○ 4. Insensitivity to vitamin D: familial vitamin D insensitivity
● Vitamin D toxicity?
○ Vitamin D is no readily excreted and stored in fat stores so can build up over time
○ Too much sun exposure actually inactivates vitamin D metabolites preventing
toxicity. Sunlight also stimulates melanin production which will further prevent
additional vitamin D production.
○ People who take too much vitamin D are at risk for vitamin D excess
○ Symptoms: polyuria, polydipsia, kidney stones as calcium is filtered out and water
follows along; anorexia, confusion, muscle weakness
● What is the latest research around vitamin D deficiency?
○ Study in JAMA 2017 showed American (39,000 participants) are consuming more
vitamin D over the time period of 1999-2014.
■ Consumption of 1000IU per day rose from 0.3% to 18%
■ Supplementation with 4000IU rose from 0.1% to 3.2%
■ 25% are supplementing with vitamin D
■ Asdfas
○ Meta-analysis of 25 studies that included more than 11,000 showed levels <
10mg/dL were less likely to suffer from colds
■ Martineau AR et. al. Vitamin D supplementation to prevent acute respiratory
tract infections: systematic review and meta-analysis of individual participant
data. BMJ. 2017 Feb 15;356:i6583. PMID: 28202713.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 16○ Journal of Modern Rheumatology showed higher pain scores and diminished
balance in Turkish fibromyalgia populations with levels < 30mg/dL
■ Kasapoğlu Aksoy M et. al. The relationship between balance and vitamin
25(OH)D in fibromyalgia patients. Mod Rheumatol. 2017 Sep;27(5):868-874.
PMID: 27846770.
○ JAMA study showed 30% decreased risk of cancer in women supplemented with
2000IU along with 1500IU of calcium (just missed statistical significance)
■ Lappe J et. al. Effect of Vitamin D and Calcium Supplementation on Cancer
Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar
28;317(12):1234-1243. PMID: 28350929.
○ Journal of Child Psychology and Psychiatry from November 2016 demonstrated in
a double-blind randomized control trial of children 3-10 years of age with autism
that vitamin D 300mg/kg (not more than 5000IU) resulted in decrease of
symptoms
■ Saad K et. al. Randomized controlled trial of vitamin D supplementation in
children with autism spectrum disorder. J Child Psychol Psychiatry. 2018
Jan;59(1):20-29. PMID: 27868194.
○ Kaiser Permanente found higher vitamin D levels at the time of breast cancer
diagnosis correlated with a 30% greater survival
■ Yao S et. al. Association of Serum Level of Vitamin D at Diagnosis With Breast
Cancer Survival: A Case-Cohort Analysis in the Pathways Study. JAMA Oncol.
2017 Mar 1;3(3):351-357. PMID: 27832250.
○ JAMA study in December 2017 was a meta-analysis of 33 randomized control
trials including 51,000 patients found that supplementation with vitamin D and/or
calcium did not lower fracture risk
■ Zhao JG et. al. Association Between Calcium or Vitamin D Supplementation and
Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review
and Meta-analysis. JAMA. 2017 Dec 26;318(24):2466-2482. PMID:
29279934.
Paper Chase #1 - Association Between Calcium or Vitamin D Supplementation
and Fracture Incidence in Community-Dwelling Older Adults: A Systematic
Review and Meta-analysis
Andrew Buelt DO and Joe Weatherly DO
Zhao JG et. al. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in
Community-Dwelling Older Adults: A Systematic Review and Meta-analysis. JAMA. 2017 Dec
26;318(24):2466-2482. PMID: 29279934.
Pearls:
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 17● The use of supplements that included calcium, vitamin D, or both compared with placebo
or no treatment was not associated with a lower risk of fractures in community-dwelling
older adults.
● Objective: investigate whether calcium, vitamin D, or a combination of calcium and
vitamin D supplements are associated with a lower fracture incidents in community
dwelling older adults.
● Background: Many guidelines recommend supplementation with vitamin D and calcium to
prevent fractures.
● Method: Meta-analysis of studies published in the past 10 years of randomized control
trials comparing calcium, vitamin D or a combination of the two to placebo or no treatment
group.
○ Included community-dwelling adults over 50
○ Excluded adults living in an institution
○ Teases out subgroups based on vitamin D or dose of calcium, frequency of calcium
supplementation, fracture history, dietary intake, baseline vitamin D
concentrations
○ Primary outcome: number of participants with a hip fracture
○ Secondary outcome: number of participants with vertebral fractures, vertebral
fractures, and total fractures
● Results: calcium, calcium plus vitamin D and vitamin D supplement alone were not
significantly associated with a lower incidence of hip nonvertebral, vertebral, or total
fractures in community-dwelling older adults.
○ subgroup analysis did not show any significant differences within subgroups based
on dose of calcium or vitamin D, gender, fracture history, dietary calcium intake,
baseline serum 25-OH vitamin D concentrations
● Bottomline: the use of supplements that included calcium, vitamin D, or both compared
with placebo or no treatment was not associated with a lower risk of fractures.
Paper Chase #2 - Association of Broad- vs Narrow-Spectrum Antibiotics With
Treatment Failure, Adverse Events, and Quality of Life in Children With Acute
Respiratory Tract Infections
Andrew Buelt DO and Joe Weatherly DO
Gerber JS et. al. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse
Events, and Quality of Life in Children With Acute Respiratory Tract Infections. JAMA. 2017 Dec
19;318(23):2325-2336. PMID: 29260224.
Pearls:
● Narrow spectrum antibiotics were associated with better clinical and patient centered
outcomes as well as lower rates of adverse events in children with otitis media, group A
strep or sinusitis.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 18● Objective: compare the effectiveness of broad versus narrow spectrum antibiotics for
acute respiratory tract infections in children.
● Method: Retrospective cohort of over 30,000 children between 6 months to 12 years of
age that were diagnosed with either acute otitis media, group A strep pharyngitis or acute
sinusitis.
○ Primary outcomes: treatment failure and adverse events at 14 days
○ Narrow spectrum: amoxicillin or penicillin
○ Broad spectrum: amoxicillin clavulanic acid, cephalosporins and macrolides
● Results:
○ Similar failure rates in broad spectrum (3.4%) and narrow spectrum (3.1%)
○ One point improvement (100 point scale) in the child quality of life score with
narrow spectrum antibiotics
○ Adverse events in broad spectrum (35%) and narrow spectrum (25%)
● Bottomline: narrow spectrum antibiotics were associated with better clinical and patient
centered outcomes as well as lower rates of adverse events in children with otitis media,
group A strep or sinusitis.
Paper Chase #3 - Percutaneous Coronary Intervention in Stable Angina
(ORBITA): A Double-Blind, Randomised Controlled Trial
Andrew Buelt DO and Joe Weatherly DO
Al-Lamee R et. al. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind,
randomised controlled trial. Lancet. 2018 Jan 6;391(10115):31-40. PMID: 29103656.
Pearls:
● In patients with medically treated angina and severe coronary sinuses, PCI did not
increase exercise time than more than the effect of a placebo procedure.
● Objective: determine whether percutaneous coronary intervention (PCI) in stable angina
provided symptomatic relief.
● Background: Almost 500,000 PCIs out of the million each year are done for stable angina
based purely on observational data.
● Method: multicenter randomized control trial of people with angina or equivalent
symptoms and at least 70% stenosis in a single vessel appropriate for PCI.
○ After enrollment, patients spent first 6 weeks in the medical optimization phase of
the protocol - they were meeting 1-3 times per week to try to optimize medications
○ Primary endpoints: difference in exercise increments between groups
● Results:
○ No significant difference between groups in terms of increment in exercise time
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 19○ Many secondary outcomes, only one of which was better in the PCI group
(dobutamine stress echocardiography)
● Bottomline: In patients with medically treated angina and severe coronary sinuses, PCI
did not increase exercise time than more than the effect of a placebo procedure.
Paper Chase #4 - Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide
Complex on Hemoglobin Concentration in Young Children With Nutritional
Iron-Deficiency Anemia: A Randomized Clinical Trial
Andrew Buelt DO and Joe Weatherly DO
Powers JM et. al. Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin
Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.
JAMA. 2017 Jun 13;317(22):2297-2304. PMID: 28609534.
Pearls:
● Ferrous sulfate resulted in greater increase in hemoglobin concentrations and higher
rates of iron deficiency anemia at twelve weeks compared with iron polysaccharide
complex.
● Objective: Compare the effect difference from ferrous sulfate versus iron polysaccharide
complex in children with nutritional iron deficiency anemia.
● Method: Double blind superiority randomized controlled trial of pediatric patients from
9-48 months of age that were found on labs and history to have nutritional iron deficiency
anemia (IDA). Took place at tertiary hematology centers in the United States.
○ Enrollees were given 3mg/kg of elemental iron daily, either as ferrous sulfate drops
or iron polysaccharide complex drops, for 12 weeks.
○ 70% of kids finished the trial, 30 kids in each arm of the trial
● Results:
○ 29% resolution of IDA in the ferrous sulfate group
○ 6% resolution of ID in the polysaccharide complex group
○ Other markers (ferritin, total iron binding capacity, iron levels) were better in the
ferrous sulfate group
○ Diarrhea was less common in the ferrous sulfate group (35% vs. 58%)
● Bottomline: Ferrous sulfate resulted in greater increase in hemoglobin concentrations and
higher rates of iron deficiency anemia at twelve weeks compared with iron polysaccharide
complex.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 20Paper Chase #5 - Reporting of Conflicts of Interest in Oral Presentations at
Medical Conferences: A Delegate-Based Prospective Observational Study
Andrew Buelt DO and Joe Weatherly DO
Grey A et. al. Reporting of conflicts of interest in oral presentations at medical conferences: a
delegate-based prospective observational study. BMJ Open. 2017 Sep 21;7(9):e017019. PMID:
28939580.
Pearls:
● In oral presentation at medical conferences, statements were often missing, displayed
too briefly to be read and understood, or not discuss or explained by the presenter.
● Objective: Assess the prevalence, location, presentation, and consistency of conflict of
interest statements in oral presentations at medical conferences
● Method: Prospective delegate-based observational study where four investigators
conducted the main outcomes: conflict of interest statement, location within the
presentation, and it's duration of display
● Results:
○ 201 presentations
○ 143 (71%) presentations included conflict of interest statement
○ 60% disclosed at least one conflict of interest and 84% reported it on a dedicated
slide
○ Average time spent on the conflict of interest slide was 2 seconds
○ 50% of the time there was a written handout with the presentation that did not
contain a conflict of interest.
● Bottomline: In oral presentations at medical conferences, statements were often missing,
displayed too briefly to be read and understood, or not discussed or explained by the
presenter.
Primary Care RAP April 2018 Written Summary | hippoed.com/pc 21You can also read
