Pr ima r y C a r e RAP O cto be r 2018 W r itte n S u …...Pr ima r y C a r e RAP O cto be r 2018 W...

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

Associate Editor Kenji Taylor MD MSc

Intro - Necrotizing Pancreatitis Aisha Lofters MD Neda Frayha MD Pearls

Severe necrotizing pancreatitis occurs in about 15-20 of cases of pancreatitis Optimal timing of debridement is 3-4 weeks after symptom onset A step up approach with less invasive measures such as percutaneous drainage followed by more invasive approaches like open debridement as needed may actually lead to improved patient outcomes

Our reader Elizabeth asked for an approach to abnormal uterine bleeding One way to think about it is anatomic systemic and medication-related Another way to approach it is ovulatory versus anovulatory

Neda had a case of a patient in his 60rsquos with recurrent gallstone pancreatitis When she

saw him in the outpatient setting and read his CT report from one week prior it said he had persistent to worsening emphysematous pancreatitis She spoke to the surgeon about him went to the literature and reviewed some learning points

Severe necrotizing pancreatitis occurs in about 15-20 of cases The Ranson Score APACHE II and now recently the Atlanta criteria grade

severity based on a combination of clinical findings blood work and imaging The Atlanta Classification mild moderate severe

Severe = persistent organ failure for more than 48 hours and local complications like parapancreatic fluid collections pancreatic necrosis (sterile or infected) pancreatic pseudocysts and walled-off necrosis

⅓ of necrotizing pancreatitis cases become infected which increases mortality from 5 to 20 In other cases the areas of necrosis will eventually wall off resolve and eventually the patient can get better

Article in BMJ Gut 2006 by Werner et al breaks down acute necrotizing pancreatitis into acute and chronic phases

Acute = initial SIRS reaction with inflammatory cytokine response Late = 2-4 weeks less inflammation clearer demarcation of necrosis from

surrounding tissues that makes debridement easier

Primary Care RAP October 2018 Written Summary | hippoedcompc

Optimal timing of surgery is 3-4 weeks after symptom onset Two indications for debridement infected or symptomatic sterile necrosis

Options for debridement Percutaneous drainage bridge to open surgery in more clinically unstable

patients but also curative about in about ⅓ of cases Endoscopic debridement limited to patients with walled-off necrosis that is

very localized Open debridement remains gold standard Step Up start with less invasive approach Iike percutaneous drainage and

then move to more invasive if necessary Studied in the PANTER study published in the NEJM 2010 with 88

patients randomly assigned to either primary open debridement v step up approach rarr step up approach had lower rates of composite outcomes (multiorgan failure perforation enterocutaneous fistula)

What happened to the patient with necrotizing pancreatitis seen in Nedarsquos office He was admitted eventually for failing to thrive placed on TPN for a week to

optimize his nutritional status and then underwent open debridement Hersquos doing well now

Listener (Elizabeth) question How do you systematically approach abnormal uterine bleeding

Classification Scheme Anatomic - fibroids polyps endometriosis hyperplasia neoplasm Systemic - PCOS obesity uncontrolled diabetes thyroid dysfunction

bleeding disorders hyperprolactinemia pregnancy perimenopause Drug-related - OCPs anticoagulants antiepileptics steroids levothyroxine

NSAIDs SSRI tamoxifen tricyclics herbal medications spironolactone Herbals - chasteberry danshen mother wart ginseng ginkgo soy

Other classification scheme (same causes just different organization) Ovulatory - regular bleeding that is either heavy or long

Thyroid dysfunction bleeding disorders endometrial polyps and fibroids

Anovulatory - irregular infrequent bleeding PCOS uncontrolled DM thyroid and hormonal issues

Stress can also affect periods References Werner J Feuerbach S Uhl W et al Management of acute pancreatitis from surgery to interventional intensive care Gut 200554426-436 Besselink MG et al Minimally invasive step-up approach versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial) design and rationale of a randomised controlled multicenter trial [ISRCTN13975868] BMC Surg 2006 Apr 1166 PMID 16606471

Primary Care RAP October 2018 Written Summary | hippoedcompc 2

De Waele JJ et al A step-up approach or open necrosectomy for necrotizing pancreatitis N Engl J Med 2010 Sep 23363(13)1286 author reply 1287 PMID 20860515 Mier J Leoacuten EL et al Early versus late necrosectomy in severe necrotizing pancreatitis Am J Surg 1997 Feb173(2)71-5 PMID 9074366 Buumlchler MW et al Acute necrotizing pancreatitis treatment strategy according to the status of infection Ann Surg 2000 Nov232(5)619-26 PMID 11066131 Banks PA et al Classification of acute pancreatitis--2012 revision of the Atlanta classification and definitions by international consensus Gut 2013 Jan62(1)102-11 PMID 23100216 Bae J Park S Kwon J-W Factors associated with menstrual cycle irregularity and menopause BMC Womenrsquos Health 20181836 doi101186s12905-018-0528-x httpwwwcfpcacontent618693tab-article-info httpswwwaafporgafp20120101p35html

Journal Club with the Curbsiders Matthew Watto MD Stuart Brigham MD Paul Williams MD Chris Chiu MD Neda Frayha MD Pearls

Article 1 Patients with cancer choosing complementary medicine in lieu of conventional medicine may have worse outcomes as a result

Article 2 Physicians with active leadership in a healthcare system have the potential to provide positive influence in many ways

Article 3 There does not appear to be enough evidence to make any conclusions and generally the exposures in marijuana use do not match that of smoking in people who develop COPD

Article 4 Patients with penicillin allergy are being prescribed antibiotics like macrolides and fluoroquinolones more frequently They are also are getting MRSA and C diff infections

The Curbsiders is a weekly podcast where they ask experts questions about internal

medicine They joined Hippo for a journal club review Article 1 Complementary Medicine Refusal of Conventional Cancer Therapy and Survival

Among Patients With Curable Cancers Background Complementary medicine is a multibillion dollar industry in the US

Prior studies have suggested up to 88 of cancer patients use complementary medicine as part of their treatment with up to ⅔ believing it will prolong their life and ⅓ believing it will cure their disease


Objective Characterize those cancer patients who are using complementary medicine and its relationship to adherence to conventional cancer treatment as well as survival

Methods Selected 258 out of 19 million cancer patients and then identified 1032 cancer patients matched by age race and cancer typestage

Findings Complementary medicine associated with

Higher refusal rates of conventional cancer treatments Poorer five year survival rates 82 v 86 that was no longer present

once they factored in adherence to conventional treatment options Bottomline Patients with cancer choosing complementary medicine in lieu of

conventional medicine may have worse outcomes as a result It is important to be proactive in discussing

Article 2 The Value of Physician Leadership Objective Examine what happens with physicians running hospitals Findings

Physician-led hospitals tend to have - Lower hospital-acquired infection rates Lower readmission rates Improved patient satisfaction More lean management Higher job satisfaction

Bottomline Physicians with active leadership in a healthcare system have the potential to provide positive influence in many ways

Article 3 Marijuana Use Respiratory Symptoms and Pulmonary Function a Systematic Review and Meta Analysis

Objective understand respiratory impact of marijuana use Method systematic review narrowing down to 22 observational studies published

between 1973 to 2018 Studies examined pulmonary function cough wheeze and dyspnea

Findings Found association between marijuana use and cough wheezing but the

overall evidence was low Evidence around pulmonary function was insufficient to make any kind of

statement Some signal in the data that airway conductance and resistance were worse

in those who used marijuana Bottomline There does not appear to be enough evidence to make any conclusions

and generally the exposures in marijuana use does do not match that of smoking in people who develop COPD

Article 4 The Risk of Methicillin-Resistant Staph Aureus and C Diff in patients with a documented penicillin allergy


Objective Assess the relationship between a penicillin allergy and the development of MRSA or C diff infection

Background 10 of all patients have a documented penicillin allergy and 95 are actually intolerant of the drug while 80 of patients who had some kind of immediate hypersensitivity to penicillin are no longer allergic after 10 years

Method prospective cohort study of 300 adults in the UK both with and without documented penicillin allergy Outcome of interest was MRSA and C diff infection and the use of non-penicillin antibiotic alternative

Results Penicillin-allergic patients had adjusted hazard ratio of 169 for MRSA and

125 for C diff infection Incidence ratios for alternative antibiotic use was 4 for macrolides and 2 for

fluoroquinolones Bottomline Patients with penicillin allergy are being prescribed antibiotics like

macrolides and fluoroquinolones more frequently They are also are getting MRSA and C diff infections

References Complementary Medicine Refusal of Conventional Cancer Therapy and Survival Among Patients With Curable Cancers Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose analysis of individual patient data from randomised trials The value of physician leadership Marijuana Use Respiratory Symptoms and Pulmonary Function A Systematic Review and Meta-analysis Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy population based matched cohort study

Diverticulosis Paul D Simmons MD and Neda Frayha MD Pearls

The classic teaching of high fiber diet for diverticulosis is not supported by the most recent evidence It may or may not help

Symptomatic uncomplicated (no diverticulitis or bleeding but colicky lower abdominal pain) diverticulosis is a clinical entity that appears to have overlap with IBS and may respond to similar treatments

Diverticular bleeding is common and up to 70 will stop on their own so stabilization until they can get colonoscopy is key

What causes diverticulosis

Vasorectal arteries penetrate through the muscularis of the colon wall and create weak spots that then can bulge into a pouch or diverticulum


Range up to 1 cm Western population predominantly left-sided Asian populations predominantly right-sided (and more as people age)

Risk factors poor GI motility Western diet How many people have it

About ⅓ of patients based on observational study of 9000 patients that had a screening colonoscopy

Studies from 1970rsquos showed 60 prevalence in people over 80 80-85 have no symptoms 15-20 with symptoms

75 colicky pain with no inflammation 25 develop diverticulitis

Total of 5 with diverticula will have diverticulitis Management

Classic teaching for incidental diverticulosis is no further work-up necessary and only a high fiber diet

Pearl Cross-sectional study in 2012 of 2100 Swedish volunteers who underwent colonoscopy and then completed food questionnaire found high fiber intake was associated with MORE diverticulosis More fiber intake was also not associated with more bowel movements Also constipation symptoms were not associated with diverticulosis

Avoiding seeds nuts popcorn has not been shown to be true May try antispasmodicsanticholinergics like dicyclomine around meals similarly to

treating IBS American Gastroenterology study in 2010 looked at overlap of IBS with

diverticulosis in 400 patients Strong association with odds ratio of 18 that if you had IBS by Rome II

criteria you would also have diverticulosis And that association was with diarrhea-predominant IBS and not constipation-predominant IBS

Pearl No association between IBS and diverticulitis Bleeding

Patients presenting with major GI bleeding most common source is diverticula and ranges vary from 17-40 Other common causes include angiodysplasias (up to 30) and ischemic colitis in elderly (up to 20)

Classically painless rectal bleeding from arterial source so it is brisk About 70 of lower GI bleeds will stop on their own Stabilization with the ABCrsquos (airway breathing circulation) is important) Up to 20 of people with diverticulosis have first presentation with

painless rectal bleeding Symptomatic Uncomplicated Diverticular Disease (SUDD)

Epi 15-20 of those with diverticular disease Symptoms


Can look similar to irritable bowel syndrome with colicky pain Relieved by passing gas or having a bowel movement Attacks after eating are common along with bloating

Swedish study in 2016 reported more diarrheal symptoms rather than constipation There appears to be some overlap with IBS

Diagnosis of exclusion Rule out malignancy colorectal cancer ovarian cancer infectious

colitis tubo-ovarian pathology pelvic inflammatory disease appendicitis Crohnrsquos and ulcerative colitis mesenteric ischemia (especially in elderly)

Colonoscopy +- abdominal CT Management

As above References Gralnek IM et al (2017 Mar 16) Acute lower gastrointestinal bleeding New Engl J Med 376 1054-1063 Jung HK et al (2010 Mar) Diarrhea-predominant irritable bowel syndrome is associated with diverticular disease a population-based study Am J Gastroenterol 105(3) 652-61 Peery AF et al (2012) A high-fiber diet does not protect against asymptomatic diverticulosis Gastroenterology 142(2) 266-72 Salzman H and Lillie D (2005 Oct 1) Diverticular disease diagnosis and management Am Fam Physician 72(7) 1229-1234 Sehgal MEJ et al (2016 Jun 21) Symptomatic diverticulosis is characterized by loose stools Clin Gastroenterol Hepatol 14(12) 1763-1770 Wilkins T et al (2009 Nov 1) Diverticular bleeding Am Fam Physician 80(9) 977-983

Communicating with Vaccine Skeptics Solomon Behar MD Paul Offit MD and Neda Frayha MD

Pearls It is understandable that parents are questioning vaccines now given that they do not

encounter the effects of these infections in their day to day life The role of the clinician is to make the consequences of vaccine preventable diseases

real for parents so that they can understand how truly scary they are

Why might parents be skeptical of vaccines Parents are no longer scared of the diseases that vaccines aim to protect children from In comparison to the twenties and thirties


when children were dying from diphtheria or becoming disabled from polio this generation of parents has not seen firsthand the effects of these infections As practitioners we are asking parents to vaccinate their children against 14 different diseases in the first year of life to prevent diseases that most people do not see using biological fluids that most people do not understand With these facts in mind Dr Offit underscores is reasonable it is for parents to be skeptical

What can practitioners do when faced with a vaccine skeptical parent The first thing to do when you see someone who is hesitant about vaccines is to ask them what they are scared of If there is a specific issue be it autism diabetes or multiple sclerosis there likely will be data to answer those questions As the clinician you try to present the data in a compelling passionate and compassionate way As Dr Offit says science alone is not good enough It is also important to make people realize that the choice not to vaccinate is not a risk free choice By referring to parent activist groups like Families Fighting Flu or National Meningitis Association you can provide parents with examples of the very serious risk associated with not vaccinating

What is Dr Offitrsquos approach to dealing with a parent that is unsure about vaccines The way that Dr Offit goes about it is as follows he finds out what the parent is worried about tries to go through how one would answer those question he talks about what has been done to answer those questions and ends by emphasizing why it is important to vaccinate He makes it personal making sure that the parent knows that he has his own children that are fully vaccinated and says that vaccinating is a matter of loving the child He tells parents that by not vaccinating their child the parent is asking him to practice substandard care

Why might parents continue to believe that autism is linked to the MMR vaccine As Dr Offit explains if you are a parent of a child that suffers from autism you want to try and figure out why What Andrew Wakefield offered was a reason why in his explanation it was the vaccine that caused the development of autism With this explanation parents were allowed some control over the disease For example parents believed that they could control whether or not their future children developed autism but choosing not to vaccinate them As practitioners we can say things like vaccines are good and vaccine protect against preventable disease but what we still cannot say is what causes autism and parents want that explanation

How can practitioners advocate for their patients Say something It is important for clinicians to speak up when they see misinformation being presented because these false claims are devaluing the truth of science


Post Intensive Care Syndrome Steve Biederman MD Neda Frayha MD Pearls

Post-intensive care syndrome (PICS) has no formal definition but includes deficits in the cognitive psychiatric and physical domain

Potential interventions include ICU diaries support groups early mobilization decreasing sedation whenever possible early nutrition and attention to sleep hygiene

Post- Intensive Care Syndrome (PICS) series of deficits that ICU survivors face in the

months to years after critical illness that includes impairment in cognitive psychiatric and physical domains

No formal definition exists and the current definition is broad however current estimates hover around 50

May last for any duration of time up to years Cognitive sequelae

Difficulties with memory executive function and visualspatial issues Brain ICU study NEJM 2013 looked at PICS patient evaluated MICU or SICU

patients at 3 and 12 months 40 at 3 months at global cognition scores below population means and

26 had score two standard deviations below population means (similar to Alzheimerrsquos disease)

25 still had deficits at 12 months 33 had deficits typically associated with moderate traumatic brain injury

Psychiatric sequelae PTSD depression and anxiety Rates in up to 60 of patients but estimates have ranged rarr we donrsquot know true

prevalence Lancet Respiratory Medicine 2014 (same cohort as Brain ICU study) -

Depression in 37 at 3 months and 33 at 12 months Symptoms mostly somatic versus cognitive

Lower rates of of PTSD at 7 at both 3 and 12 months Physical sequelae

Weakness neuropathy joint contractures and other deficits depending on the illness itself (ie lung issues if it was a pneumonia)

Journal of Critical Care Medicine 2014 article of multi-site prospective study with longitudinal follow-up for ICU survivors of lung injury at 3 6 12 and 24 months

⅓ had evidence of muscle weakness at hospital discharge that decreased but persisted over time

NEJM study in 2011 found in 109 ARDS survivors that after 5 years there was no objective weakness but all reported subjective weakness and the 6-minute walk test was 76 lower than expected despite normal PFTs


Median age was 44 and 83 had no co-existing medical condition and worked full time

Risk factors Co-existing chronic medical or psychiatric illness Duration of sedation and delirium

Preventive measures ICU diaries have been shown to decrease rates of PTSD Early mobility decreasing sedation early nutrition may also help but there is no

data yet to support it Treatment

Treat each morbidity as would be standard Supportrecovery groups

2018 Society of Critical Care Medicine Annual Congress had an abstract where weekly unstructured meetings led by a chaplain or social worker to discuss experiences fears and challenges of recovery over 10 months among 82 attendees led to 93 feeling emotionally supported

Resource for patient wwwmyicucareorgthrive gives information and resources to patients

References Herridge MS Tansey CM Matte A et al Functional disability 5 years after acute respiratory distress syndrome N Engl J Med 20113641293-1304 httpwwwnejmorgdoifull101056NEJMoa1011802 Jackson JC Pandharipande PP Girard TD et al Depression Posttraumatic Stress Disorder and Functional Disability in Survivors of Critical Illness results from the BRAIN ICU (Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors) Investigation A Longitudinal Cohort Study The Lancet Respiratory Medicine 20142(5)369-379 doi101016S2213-2600(14)70051-7 Jensen JF Thomsen T Overgaard D et al Impact of follow-up consultations for ICU survivors on post-ICU syndrome a systematic review and meta-analysis Intensive Care Med 201541763-75 httpsdoiorg101007s00134-015-3689-1 Jones C Baumlckman C Capuzzo M et al Intensive care diaries reduce new onset post traumatic stress disorder following critical illness a randomised controlled trial Critical Care 201014(5)R168 httpdoiorg101186cc9260 Mehlhorn J Freytag A Schmidt K et al Rehabilitation interventions for post intensive care syndrome a systematic review Crit Care Med 201442(5)1263-71 doi 101097CCM0000000000000148 Needham DM Davidson J Cohen H et al Improving long-term outcomes after discharge from intensive care unit report from a stakeholdersrsquo conference Critical Care Medicine 201240(2)502-9 httpsinsightsovidcomcrossrefan=00003246-201202000-00020


Needham DM Feldman DR Kho MK The functional costs of ICU survivorship collaborating to improve post ICU disability American Journal of Respiratory and Critical Care Medicine 2011183(8)962-4 httpswwwatsjournalsorgdoifull101164rccm201012-2042EDreadcube-epdf Pandharipande PP Girard TD Jackson JC et al Long-term cognitive impairment after critical illness N Engl J Med 2013 3691306-16 DOI 101056NEJMoa1301372 Thomas S Burridge JH Pohl M et al Recovery of sit-to-stand function in patients with intensive care unit acquired muscle weakness results from the General Weakness Syndrome Therapy cohort study J Rehabil Med 201648(9)793-8 doi 10234016501977-2135 Volk B Grassi F Treatment of the post ICU patient in an outpatient setting American Family Physician 200979(6)459-64 httpspdfssemanticscholarorga3a48aa5b32f60d7e4121aba02ccf42049b76daepdf

Anticoagulation - Direct Oral Anticoagulants (DOACs) Tom DeLoughery MD Matthieu DeClerck MD Pearls

There are five DOACs dabigatran is a thrombin inhibitor and rivaroxaban apixaban and edoxaban are factor Xa inhibitors

They are easier to take often times cheaper and more effective in anticoagulation for atrial fibrillation DVTs and pulmonary emboli

Special populations where caution is warranted include those who are overweight underweight elderly or have a mechanical valve or renal insufficiency

Prothrombin complex concentrates can be used to reverse the factor Xa inhibitors while idarucizumab can be used to reverse dabigatran However reserve for life-threatening bleeding as there is a risk of thrombosis

The pendulum has swung in favor of restarting DOACs soon after both GI and intracranial bleed

Direct Oral anticoagulants

Dabigatran - thrombin inhibitor Rivaroxaban apixaban edoxaban - factor Xa inhibitor

Benefits Easier - one pill once or twice a day less monitoring or food or drug interactions

like those on warfarin Often times cheaper than low molecular weight heparin More effective in atrial fibrillation and DVTPE treatment

Dabigatran - less ischemic stroke in atrial fibrillation Apixaban - less overall stroke in atrial fibrillation All Xa inhibitors are safer for DVT treatment than warfarin

Cons Not as effective if you have a mechanical heart valve


Fixed dose so unclear how weight extremes impact drug pharmacokinetics Not all reversible

However outcomes are actually no different rarr how important is this issue of reversibility

Dabigatran now has a very specific reversal agent idarucizumab (ldquoI dare you to bleedrdquo) In clinical studies people still bled 2-11 hours after receiving it

Special populations Overweight - no specific guidelines and unclear if like other anticoagulants these

patients actually need more drugs to be therapeutic If gt 120kg maybe donrsquot use for atrial fibrillation If gt 140kg maybe donrsquot use for thrombosis

Underweight If lt 50kg maybe donrsquot use for anticoagulation at all

Elderly More at risk for bleeding and clotting however they benefit the most from

anticoagulation May benefit for the anticoagulation visits

Mechanical valves - DOACs donrsquot work as well possibly they are not inhibiting the contact pathway (clotting on the valve) or the dosage is not right or aspirin needs to be added

Renal insufficiency - increased risk of bleeding and thrombosis Needs to be renally adjusted or not used at all

Dabigatran - donrsquot use if CrCl lt 50 Rivaroxaban and apixaban require adjustment but there is some

data behind use in dialysis First-line for Dr DeLoughery in renal patients is either low molecular

weight heparin or apixaban (especially in outpatient setting) What to do with the elderly patient on a DOAC who has a fall and now has a subdural or

intracranial hemorrhage Factor Xa inhibitors - prothrombin complex concentrates (PCC)

Can dose them by INR or give them 50 unitskg to reverse the INR within 15 minutes

Dabigatran - idarucizumab 5g less than 2 will also need re-reversal in 8 hours Warfarin - remember with warfarin to throw in 10mg of vitamin K for when the

PCC wears off Low molecular weight heparin (LMWH) - protamine sulfate 1mg for every 1mg of

LMWH Can get anaphylactoid reactions with it

Unless there is hemorrhaging avoid fresh frozen plasma and other specific blood products

Pearl reserved for life-threatening bleeding because risk of reversal is thrombosis When to restart after a bleed


GI bleed - restart anticoagulation Studies have demonstrated decreased rate of thrombosis decreased

mortality and no increased risk of GI bleed recurrence Good idea to get a colonoscopy to make sure there is not a lesion that needs

to be managed Intracranial hemorrhage - discuss with neurosurgeon colleagues and consider

restart anticoagulation Similar data with GI bleeds is emerging

Restarting is particularly a strong consideration if you have an elderly patient with afib

Data on when to restart is limited but can be as soon as a week after the event References httpswwwnejmorgdoifull101056NEJMoa1007903 httpswwwnejmorgdoifull101056NEJMoa1113572 httpswwwnejmorgdoifull101056NEJMe1012149 httpswwwaccorglatest-in-cardiologyarticles201703030742reversing-oral-anticoagu lants-new-possibilities-lingering-misconceptions httpswwwnejmorgdoifull101056NEJMoa1111096 httpswwwnejmorgdoifull101056NEJMoa1711948 httpswwwnejmorgdoifull101056NEJMoa1300615 httpswwwnejmorgdoifull101056NEJMe1610510 httpswwwncbinlmnihgovpmcarticlesPMC5529093


Hospitalist Corner Common Diabetes Mistakes Maj Cina MD Neda Frayha MD Pearls

Your goals for diabetes management in hospitalized patients should be preventing hypoglycemia ketoacidosis and severe hyperglycemia

Goal range blood glucose for inpatients is 140 to 180 Hold oral meds and opt for insulin both basal and prandial Check an A1c if not done in the past 3 months to help guide discharge planning

What are the most important goals when caring for inpatients with diabetes

Prevent bad outcomes - hypoglycemia ketoacidosis severe hyperglycemia Inpatient goals

ADA 2018 guidelines defined hypoglycemia as serum glucose lt 70 severe event as less than 54 and with neurologic complication such as confusionfallaspirationseizure

If they become hypoglycemic re-evaluate what yoursquore doing so they donrsquot become hypoglycemic again

Goals for non-ICU inpatient 140-180 Glucose gt200 and lt140 were associated with worse mortality and stroke

outcomes What do you do with oral meds

Hold oral meds - patients are on a different diet and often times inconsistent diet because they are NPO for proceduressurgery Also oral meds may have less predictable pharmacokinetics

What about home insulin In Type 1 diabetes patients (and advanced Type 2) basal insulin usually not

reduced to less than 75 but will often stay at 100 In Type 2 diabetes patients typically continue at 75 to 100 of usual dose

especially if normoglycemic or hyperglycemic on admission May be less if they are going to NPO

Preventing ketoacidosis think of DKA as an insulin deficiency Identify those patients who really need basal insulin (ie Type 1 or advanced Type

2) Insulin allows the body to use glucose intracellularly to produce ATP If insulin is

not around the body has to rely on fat stop to produce ATP which leads to ketone bodies that are acidic

For those patients who are NPO on basal insulin you may want to add dextrose Preventing hyperglycemia

To get the long-acting insulin need take 15th of the weight of the patient in kilograms that can then be divided into a once daily long-acting dose or twice daily dosing


To get the prandial insulin need take 120th of the weight of the patient in kilograms for the insulin need at each meal

ADA 2018 Guidelines Recommend 02 to 03 UnitsKg for basal regimen and 005-01 UnitsKg for meal

boluses Check an A1c if not done in the past 3 months to help with discharge planning An

A1c gt9 almost guarantees need for insulin This has been shown to reduce risk of readmission for hyperglycemia

References AACEACE Diabetes Guidelines Endocr Pract 201521501 Diabetes Care in the Hospital Standards of Medical Care in Diabetes - 2018 American Diabetes Association Diabetes Care 2018 Jan 41(Supplement 1)S144-S151 Kodner C Anderson L Pohlgeers K Glucose management in hospitalized patients American Family Physician 201796(10)648-54 Magaji V Johnston JM Inpatient management of hyperglycemia and diabetes Clinical Diabetes 201129(1)3-9 Umpierrez GE et al Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery) Diabetes Care 2011 Feb34(2)256-61 Doi 102337dc10-1407 Epub 2011 Jan 12 PMID 21228246

Fluoroquinolones Risks to Patients and Providers Matt DeLaney MD Pearls

The risks of fluoroquinolones include tendinopathyrupture central nervou system effects such as chronic pain and aortic aneurysmdissection

In order to protect against lawsuits consider shared decision-making and documentation of that conversation in the chart

Tendinopathy and rupture

FDA warning in 2008 Risk is 4 times greater than average risk of a healthy person Additional factors put patients at increased risk (about 10-15 times)

Male Over age of 60 Chronic renal disease Chronic steroids (46 times risk)


Neuropathy FDA black box warning based on case reports Not much guidance in the literature about options but the potential impact is there

Central nervous system May include debilitating pain

Aortic aneurysm or dissection Case reports Postulate fluoroquinolones may weaken collagen or degrade it Largest study so far of 350000 people who received fluoroquinolones and

350000 people who received amoxicillin rates of dissectionaneurysm 60 days after first dose of fluoroquinolone were doubled

Sex and age did not seem to predict risk After 60 days risk went back down to baseline

FDA has not issued a warning given the lack of information but issued this statement prior to the above study

Lawsuits In 2011 there were 2500 lawsuits just involving tendinopathy and fluoroquinolone

use prior to these additional concerns around neuropathy chronic pain and aortic dissectionaneurysm

What to do with the risks of the medication versus the medicolegal risk Avoid in patients who have multiple risk factors or pre-existing issues such as

tendonitis chronic pain neuropathy or aortic aneurysms Discuss with patients and document in the chart

References Beware of fluoroquinolones Your your patient and the FDA Pasternak B et al Fluoroquinolone use and risk of aortic aneurysm and dissection nationwide cohort study BMJ 2018 Mar 8360k678 PMID 29519881 Klauer K Fluoroquinolones The risk behind the drug Emerg Phys Monthly (August 18 2011)

Paper Chase 1 - Effective Screening with Primary Cervical HPV Testing Versus Cytology Testing on High-Grade CIN at 48 Months Andrew Buelt DO Joe Weatherly DO Ogilvie GS et al Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months The HPV FOCAL Randomized Clinical Trial JAMA 2018 Jul 3320(1)43-52 PMID 29971397


Pearls HPV testing alone detects cervical neoplasia earlier and more accurately than cytology

Objective Determine if cervical cancer screening using primary cervical human

papillomavirus testing compared with cytology results in a lower likelihood of CIN 3 grade 3 or worse at 48 months

Method Randomized control trial of 19000 women in Canada comparing HPV testing alone versus liquid cytology testing At exit of the study at 48 months both group received both HPV and cytology testing Primary endpoint was CIN 3+ at 48 months

Results HPV-negative women by cytology had a lower cumulative incidence of CIN3+ at 48

months than cytology-negative women rarr risk ratio of 025 Bottomline HPV testing alone detects cervical neoplasia earlier and more accurately than

cytology

Paper Chase 2 - Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States Andrew Buelt DO Joe Weatherly DO Qato DM et al Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States JAMA 2018 Jun 12319(22)2289-2298 PMID 29896627 Pearls

Use of medications that may cause depression is common and increasing numbers of those medications are associated with a higher likelihood of depression

Objective evaluate the association between the use of medications that have the

potential adverse effect of depression Method NHANES (National Health and Nutrition Examination Survey) a representative

cross-sectional surveys of US adults aged 18 years or older was analyzed to find those patients on medications that can cause depression and those that then had a PHQ-9 of greater than 10

PHQ-9 has a sensitivity and specificity of 88 for detection of depression in the primary care adult population

Results Approximately 38 of adults surveyed were on medications with depression as a

possible adverse event Almost 10 were on 3 or more medications with depression as a potential side effect

Those that took 3 or more were 107 more likely to have depression compared to those not using such medications


The prevalence of depression goes from 6 to 15 when you go from using 1 to 3 drugs with depression as a potential adverse side effect

Bottomline Use of medications that may cause depression is common and increasing numbers of those medications are associated with a higher likelihood of depression

Paper Chase 3 - Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss Andrew Buelt DO Joe Weatherly DO Schreiber CA et al Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss N Engl J Med 2018 Jun 7378(23)2161-2170 PMID 29874535 Pearls

Pretreatment with mifepristone followed by treatment with misoprostol for early pregnancy loss was much better and you should probably change your practice

Objective compare the efficacy and safety of pretreatment with mifepristone followed by

treatment with misoprostol versus misoprostol use alone for the management of early pregnancy loss

Background A woman comes in with a nonviable pregnancy between 5 and 12 weeks with a closed os Misoprostol in the setting of a closed os will require another dose or manual uterine aspiration in 15-40 of those women Is there a more effective option

Method Randomized control trial of 300 women with nonviable uterine pregnancy who received mifepristone PO 24 hours prior to misoprostol 800 mcg compared to just misoprostol

Primary outcome gestational sac expulsion by initial follow up (median 48 hours) no additional intervention in 30 days (manual uterine aspiration)

Results Mifepristone + misoprostol 84 sac expulsion 9 needed additional intervention Misoprostol alone 67 sac expulsion 24 needed additional intervention Number needed to treat for benefit was between 6 and 7

Bottomline Pretreatment with mifepristone followed by treatment with misoprostol was much better and you should probably change your practice

Paper Chase 4 - Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke Andrew Buelt DO Joe Weatherly DO Amarenco P et al Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke N Engl J Med 2018 Jun 7378(23)2182-2190 PMID 29766771


Pearls Flat risk of 64 over the five years following a TIA or minor ischemic event

Objective Evaluation of the five-year risk of stroke and vascular events after a TIA Method

61 sites 21 countries using the tiaregistryorg project almost 4000 patients Funded in part by AstraZeneca Sanofi Bristol-Meyers Squibb Primary outcome stroke ACS or death from cardiovascular death

Results Predictors of recurrent stroke large artery atherosclerosis cardioembolism and an

ABCD2 score gt 4 Rate of recurrent stroke in years 1 and then years 2-5 was 64 Follow-up rate was 87 which may have affected the confidence intervals

Bottomline Flat risk of 64 over the five years following a TIA or minor ischemic event

Paper Chase 5 - Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA Andrew Buelt DO Joe Weatherly DO Johnston SC et al Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA N Engl J Med 2018 Jul 19379(3)215-225 PMID 29766750 Pearls

For those patients with a minor ischemic stroke or high-risk TIA who received combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days compared to those who received aspirin alone

Objective Test on an international population if the combination of aspirin and

clopidogrel would be helpful after a minor ischemic stroke or TIA Background The CHANCE trial showed a 32 lower risk of stroke recurrence among

Chinese patients treated within 24 hours of a TIA with aspirin and clopidogrel than those treated with aspirin alone Does those results extend to non-Chinese

Method Data from the POINT (platelet-oriented inhibition in new TIA and minor ischemic stroke) trial The POINT trial had patients from 10 countries (82 were from the US) randomized to clopidogrel+aspirin versus aspirin+placebo alone Randomized within 12 hours after ischemic stroke with NIHSS score lt 3 (higher score = worse stroke) and high-risk TIA (ABCD2 gt 4)

Primary outcome composite ischemic stroke MI or death from ischemic vascular causes within 90 days of index event

Primary safety outcome hemorrhage Results


Patients receiving dual-platelet (aspirin + clopidogrel) experienced less ischemic events vs aspirin alone (5 v 65)

Patients receiving dual-platelet (aspirin + clopidogrel) experienced more major hemorrhage vs aspirin alone (09 v 04)

No significant difference between groups in the rates of hemorrhagic stroke or intracranial hemorrhage Rather the difference was from things like GI bleeds

Bottomline Those patients with a minor ischemic stroke or high-risk TIA who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days compared to those who received aspirin alone


Optimal timing of surgery is 3-4 weeks after symptom onset Two indications for debridement infected or symptomatic sterile necrosis

Options for debridement Percutaneous drainage bridge to open surgery in more clinically unstable

patients but also curative about in about ⅓ of cases Endoscopic debridement limited to patients with walled-off necrosis that is

very localized Open debridement remains gold standard Step Up start with less invasive approach Iike percutaneous drainage and

then move to more invasive if necessary Studied in the PANTER study published in the NEJM 2010 with 88

patients randomly assigned to either primary open debridement v step up approach rarr step up approach had lower rates of composite outcomes (multiorgan failure perforation enterocutaneous fistula)

What happened to the patient with necrotizing pancreatitis seen in Nedarsquos office He was admitted eventually for failing to thrive placed on TPN for a week to

optimize his nutritional status and then underwent open debridement Hersquos doing well now

Listener (Elizabeth) question How do you systematically approach abnormal uterine bleeding

Classification Scheme Anatomic - fibroids polyps endometriosis hyperplasia neoplasm Systemic - PCOS obesity uncontrolled diabetes thyroid dysfunction

bleeding disorders hyperprolactinemia pregnancy perimenopause Drug-related - OCPs anticoagulants antiepileptics steroids levothyroxine

NSAIDs SSRI tamoxifen tricyclics herbal medications spironolactone Herbals - chasteberry danshen mother wart ginseng ginkgo soy

Other classification scheme (same causes just different organization) Ovulatory - regular bleeding that is either heavy or long

Thyroid dysfunction bleeding disorders endometrial polyps and fibroids

Anovulatory - irregular infrequent bleeding PCOS uncontrolled DM thyroid and hormonal issues

Stress can also affect periods References Werner J Feuerbach S Uhl W et al Management of acute pancreatitis from surgery to interventional intensive care Gut 200554426-436 Besselink MG et al Minimally invasive step-up approach versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial) design and rationale of a randomised controlled multicenter trial [ISRCTN13975868] BMC Surg 2006 Apr 1166 PMID 16606471












































































































































































































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