Another(year(goes(by .Another($60,000( drug ..and(thatis ... ·...

Another year goes by….Another $60,000 drug…..and that is the cheap one!

Jill Endres, MD MS Jason Wilbur, MD

Mark A. Graber, MD MSHCE FACEP

Acetaminophen…safe in pregnancy? •  Prenatal APAP use has previously been shown to be associated with ADHD in offspring…confounders? –  IndicaMons for APAP use –  Parental ADHD – Mothers with ADHD are less tolerant of pain

•  Norwegian Registry of 113,000 children (2246 with ADHD) included prepregnancy APAP use and indicaMons, parental ADHD symptoms

Ystrom E et al. Pediatrics 2017 November

Acetaminophen…safe in pregnancy?

•  Maternal APAP use during pregnancy: – <7 days ADHD HR 0.9 – >7days dose-‐dependent increase in ADHD – >28 days ADHD HR 2.1-‐2.6

•  Prepregnancy use not linked to ADHD •  Paternal preconcepMon use >28 days – ADHD HR 2.1

New “rule out” protocol Poldervaart JM et al. Effect of using the HEART score in pa=ents with chest pain in the emergency department: A stepped-‐wedge, cluster randomized trial. Ann Intern Med

2017 Apr 25; [e-‐pub]. Pickering JW et al. Rapid rule-‐out of acute myocardial

infarc=on with a single high-‐sensi=vity cardiac troponin T measurement below the limit of detec=on: A collabora=ve

meta-‐analysis. Ann Intern Med 2017 Apr 18; [e-‐pub].

5

HEART Score •  History, Electrocardiogram, Age, Risk factors, and Troponin level

•  See MD-‐Calc •  Gives you risk of MACE (major adverse cardiac event)

•  Low risk is .9-‐1.7% in 30 days of MACE If low risk……

6

Troponin + EKG-‐-‐Meta-‐analysis •  11 studies, 9241 paMents. •  2825 considered low risk. •  Looked at troponin + ECG •  Outcome: – MI during hospitalizaMon (primary outcome) – MACE (major adverse cardiac event) – Death

8

•  Nega5ve High sensi5vity troponin T (hs-‐cTnT)> 3 hours aier onset of pain<0.005ug/L+ Non-‐ischemic EKG

•  Only 0.25% risk of MI during hospitalizaMon. NegaMve predicMve value of 99.3%

9

Remember these are folks you think have a low risk of cardiac disease

•  Very low risk of cardiac disease. Shared decision making.

•  Note that EKG and Troponin are part of the “HEART” score.

•  Remember you will want to admit unstable angina.

10

Opioids for Chronic Pain •  Krebs EE et al. Effect of Opioid vs Nonopioid MedicaMons on Pain-‐Related FuncMon in PaMents With Chronic Back Pain or Hip or Knee OsteoarthriMs Pain: The SPACE Randomized Clinical Trial. JAMA 2018;319(9):872-‐82.

•  First, a linle context…

The Linle Opioid Lener That Traveled Around the World

Over-‐cite? •  Leung PTM et al. NEJM 2017;376:2194 – Porter lener was cited 608 Mmes from 1980 -‐ 2016 – 11 other NEJM leners published in 1980 were cited a median of 11 Mmes over the same follow up period

CitaMons of the 1980 NEJM Lener in the Medical Literature

Back to the Present •  240 PaMents in the Minneapolis VA system •  12 month randomized, outcome-‐masked •  Subjects – Mean age 58 years –  87% men –  87% white –  2/3 with chronic back pain; 1/3 with chronic hip and/or knee pain from OA

Design •  Opioid group

1.  Morphine IR, oxycodone IR, hydrocodone

2.  CR morphine or oxycodone 3.  TD fentanyl

•  Non-‐opioid group 1.  APAP or NSAID 2.  Adjuvant oral (nortrip,

amitrip, gaba) or topical (lidocaine, capsaicin)

3.  Pregaba, duloxeMne, tramadol

•  CollaboraMve pain care model

•  IntervenMons directed by a pharmacist

•  Follow up monthly unMl “stable” then every 1-‐3 months, mostly by phone

•  Aim to improve “PEG” scores and reach paMent-‐idenMfied goals

•  No outside pain meds but nonpharmacologic tx encouraged

Outcomes •  Primary Outcome – pain-‐related funcMon, per Brief Pain Inventory; PaMent-‐reported adverse events

•  Secondary Outcomes – mulMple pain, funcMon and mood scales; hospital visits; opioid misuse scales

Results •  Excellent follow up and very linle dropout •  Opioid group tried a median of 2 study drugs, 85% of paMents used less than 50mg morphine equivalent per day (max 100mg)

•  Non-‐opioid group tried a median of 4 (APAP, NSAIDs, topicals, adjuvant – not much tramadol)

Results •  No difference in mean BPI interference scores at end of study – Opioid group change: 5.4 à 3.4 – Non-‐opioid group change: 5.5 à 3.3

•  More in non-‐opioid group had >/=30% reducMon in BPI pain severity score (53.9% vs 41%)

•  Opioid group had significantly more medicaMon-‐related symptoms at 12 months

Take Home Points •  Low-‐moderate intensity opioid use for chronic musculoskeletal pain is not superior to a non-‐opioid strategy

•  Opioid use is associated with more adverse events than a non-‐opioid strategy

•  Opioids may be associated with worse pain control

•  This does NOT apply to cancer paMents, acute pain, etc.

New Pediatric Hypertension Guidelines

•  2017 AAP Clinical PracMce Guideline (expert opinion)

•  DefiniMons (based on age, sex, height) – Normal: <90%ile –  Elevated BP: 90%ile to <95%ile or >120/80 (no longer called prehtn)

–  Stage 1 HTN: 95%ile to 12 mm Hg above 95%ile or 130-‐139/80-‐89

–  Stage 2 HTN: Above 12 mm Hg over 95%ile or 140/90


•  Office BP measurement – Check annually for kids age 3 and over – every visit if obese or high risk

•  Home BP monitoring – Use ABPM in kids over 5 with HTN >1 year, WCH, high-‐risk, starMng Rx

– Do not use home BP monitors for diagnosis


•  Other tesMng –  EKG not recommended – Avoid other invesMgaMon in kids >6 yo if FH and/or no suspicion of secondary

–  Echocardiogram to eval for LVH if starMng Rx •  Treatment – DASH diet and exercise plan at Mme of diagnosis –  Rx if LSM fail

The opiate crisis: Should we use non-‐narcoMc pain meds in the ED?

Chang AK et al. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department: A randomized clinical

trial. JAMA 2017 Nov 7; 318:1661. (hnp://dx.doi.org/10.1001/jama.2017.16190)

This one got lots of press: opiates are no bener than acetaminophen,

etc. Not –so-‐-‐ fast.

•  Double-‐blind, randomized, controlled trial in paMents with extremity pain. 411 paMents

•  Four oral analgesic regimens: –  ibuprofen 400 mg plus acetaminophen 1000 mg, –  oxycodone 5 mg plus acetaminophen 325 mg, –  hydrocodone 5 mg plus acetaminophen 300 mg, –  codeine 30 mg plus acetaminophen 300

•  11 point scale iniMally then at 4 hours mg.

•  Mean pain score: 8.7. •  At two hours, there were no staMsMcally significant differences in pain reducMon among treatment groups.

•  ReducMons in pain scores ranged from 4.4 points in the oxycodone plus acetaminophen group to 3.5 with hydrocodone and acetaminophen.

So no benefit to narcoMcs??

No, not really. Another terribly done study.

•  Under dosed acetaminophen in the narcoMc groups.

•  If had used adequate acetaminophen may have been a difference in pain reducMon.

•  By the way, why only 400mg Ibuprofen? This is the ceiling dose for pain control. www.medscape.com/viewar=cle/574279

Which AnMdepressants Are Best? •  Cipriani A, et al. ComparaMve efficacy and acceptability of 21

anMdepressant drugs for the acute treatment of adults with major depressive disorder: a systemaMc review and network meta-‐analysis. Lancet, 2018. Online: hnps://doi.org/10.1016/S0140-‐6736(17)32802-‐7

•  SystemaMc review and network meta-‐analysis: – RCTs only; placebo controlled and head-‐to-‐head comparisons

– Group level data compared – 522 trials included; 116,000 parMcipants – 21 anMdepressants compared: •  Efficiency -‐ >/=50% reducMon in score on standardized depression raMng scale at 8 weeks •  Acceptability – dropout rate from trials

EffecMveness

Conclusions •  All anMdepressants more effecMve than placebo for treaMng MDD in adults (J)

•  RelaMvely higher response / lower dropout rates for escitalopram, mirtazapine, sertraline, paroxeMne

•  Lower response rate / higher dropout rate for trazodone and fluvoxamine

•  No paMent-‐level data to guide treatment for specific populaMons

Firearms Storage •  Cross-‐secMonal analysis of online probability survey of US adults with children (2015) – Firearm ownership •  Storage

– Child with self-‐harm risk behaviors •  Depression •  ADHD •  Other mental health condiMons

Scon J, et al. Pediatrics. 2018; 141(3): e20172600

Firearm Risk •  34.8% of homes had firearms

•  42.4% of parent homes with children had firearms – 43.5% of homes with children with self-‐harm risk – 42.3% of homes with children without idenMfied increased risk

Firearm risk •  33% of parents store all guns unloaded and locked – 31.8% in homes with children without idenMfied increased risk

– 34.9% in homes with children with self-‐harm risk

average risk

locked/unloaded

loaded/locked or unloaded/unlocked

unlocked and loaded

increased risk

PCI or medical treatment for stable angina

Percutaneous coronary interven5on in stable angina (ORBITA): a double-‐blind,

randomized controlled trial Lancet Volume 391, No. 10115, p31–40, 6 January 2018

•  230 paMents with stable angina and at least 70% occlusion of one vessel

•  OpMmized medical management + or – PCI •  PaMents were assessed with cardiopulmonary exercise tesMng, dobutamine echocardiography, and symptom and quality-‐of-‐life quesMonnaires both before and aier procedures.

•  Treadmill Mme zero and 6 weeks •  No difference in treadmill Mmes between two groups.

•  500 seconds mean at start (both groups) •  28 seconds more in PCI, 12 seconds more in medical

•  No difference in angina symptoms

•  Bener wall moMon in PCI group (therefore revascularizaMon in those with CHF).

•  Does not apply to those with unstable angina or MI!

•  (see hnps://www.jwatch.org/na45614/2017/12/27/percutaneous-‐coronary-‐intervenMon-‐paMents-‐with-‐stable)

Does low dose ASA increase hemorrhagic stroke?

Cea Soriano L et al. Low-‐dose aspirin and risk of intracranial bleeds: An observa=onal study in UK general prac=ce. Neurology

2017 Nov 28; 89:2280.

•  1:1 matched cohort study •  200,000 new users of aspirin (low dose) •  200,000 matched controls •  Not randomized… •  Aged 40-‐84, median age 64; 51% men •  Followed for 5.4 years •  75-‐300mg ASA/day

Subgroups

•  1611 cases of intracranial bleeding occurred (46% intracerebral hemorrhage, 30% subdural hematoma, and 24% subarachnoid hemorrhage).

•  Low-‐dose aspirin was not associated with excess risk for intracranial bleeding (all types same) overall (rate raMo, 0.98)

Carte blanche? •  Findings are generally consistent with other studies (some show increased but small risk; others don’t)

•  This supports the safety of primary prevenMon with aspirin as per USPSTF (adults 50-‐59 with >/=10% 10-‐year CVD risk and low bleed risk)

Choosing Wisely Peds Orthopedics

•  Don’t screen for DDH with US in low risk infants with normal exam

•  In-‐toeing gait in kids under 8 should not be treated

•  AsymptomaMc children with flexible flat feet should not use orthoMcs.

•  MRI and CT shouldn’t be first line tests in kids •  Torus fractures don’t require radiographic follow-‐up once pain resolves.

Choosing Wisely Peds Endocrine

•  Five tests to avoid: – Hormone tests (LH, FSH, Testosteroine, Estradiol) in prepubertal kids with pubic hair or body odor.

–  Screening for chronic illness or endocrine condiMons in kids above the 3%ile for height and appropriate growth.

–  Vitamin D in healthy kids (regardless of weight) –  Thyroid or insulin levels in obese children –  Thyroid ultrasound in kids with simple goiter or autoimmune thyroidiMs.

The sun is coming out… •  USPSTF recommendaMon (B) : – Counsel fair-‐skinned paMents age 6 m-‐24 yrs about reducing exposure to UV-‐B

– Used to be age 10+

•  Older individuals might benefit as well (level C evidence)

Should we use thrombolysis for DVT?

Vedantham S et al. Pharmacomechanical catheter-‐directed thrombolysis for deep-‐vein thrombosis. N Engl J Med 2017 Dec 7;

377:2240.

•  Previous study shows it is terrible: higher PE rate, higher vena caval filter rate, higher transfusion rate.

•  Within 2 years many get post thromboMc syndrome.

This paper: •  691 paMents with symptomaMc proximal DVT •  Yes or no pharmacomechnical thrombolysis •  24 months no difference in posnhromboMc syndrome 47% •  Moderate-‐to-‐severe PTS occurred more oien in the control

group (24% vs. 18%), and severity of PTS was significantly greater in this group at all visits between 6 and 24 months.

•  Quality of life the same •  However, quality-‐of-‐life measures were similar in both

groups. •  6 had major bleeding.

•  So…use only when there is phlegmasia (which is basically a compartment syndrome).

•  Consistent with Chest guidelines: Use only when there is impending gangrene.

Are steroids useful in bronchiMs?

Hay AD et al. Effect of oral prednisolone on symptom duraMon and severity in nonasthmaMc adults with

acute lower respiratory tract infecMon: A randomized clinical trial. JAMA 2017 Aug 22; 318:721.

•  Looked at paMents with lower respiratory tract infecMon but no pneumonia (assumed, not explicitly stated).

•  401 adults, mean age, 47 [SD, 16.0] years; –  63% women; –  17% smokers; –  77% phlegm; –  70% shortness of breath; –  47% wheezing; (only 6% wheezing on exam). –  46% chest pain; –  42% abnormal peak flow

•  PaMents with COPD or asthma or who “needed” anMbioMcs excluded.

•  Randomized to prednisolone 40mg for 5 days or placebo and followed for 8 weeks.

•  No difference in moderate or bad cough at 5 days, symptom severity or peak flow.

•  But…only 6% were wheezing.

Asthma flares…is more ICS bener? Global Ini5a5ve for Asthma guidelines currently recommend increasing ICS

4x when symptoms increase. Does this work?

STICS Trial -‐ Children •  254 children (5-‐11) with

mild to moderate asthma on low-‐dose ICS

•  Randomized, double-‐blind study –  Usual ICS dose –  Increase ICS 5x for 7 days

•  Followed for 48 weeks

Adolescents and adults •  1922 adolescents and adults

with asthma on ICS •  Randomized unblinded

–  Usual ICS dose –  4x ICS dose for 7-‐14 days

•  Followed for one year

Jackson DJ et al. N Engl J Med2018 Mar 8. McKeever T et al. N Engl J Med2018 Mar 8.

Probably not. Children •  ExacerbaMon rates-‐ NS •  Symptom scores – NS •  Albuterol use-‐ NS •  Days of asthma control -‐ NS •  High-‐dose ICS group

–  16% more ICS exposure –  Slower linear growth (0.23 cm

annually), p = 0.06

Adolescents and adults •  Time to first severe

exacerbaMon-‐ aHR 0.81 –  45% vs 52%

•  19% fewer severe exacerbaMons in the high-‐dose ICS group (NNT 15)-‐ NS

•  High-‐dose pts more likely to experience –  Dysphonia –  Oral candidiasis

Where there’s smoke, there’s… •  psychosis…maybe.

•  Pot smoke, that is.

Pot smoking and Psychosis •  Longitudinal survey 5300 adolescents in UK

–  Self-‐report cigarene and cannabis use age 14-‐19 –  Structured interviews for psychoMc experiences at age 12 and 18.

•  Both tobacco (EA) and cannabis (EA and LA) associated with psychosis –  MVA (alcohol use, family Hx substances abuse, childhood trauma,

IQ) did not alter results –  Controlling for confounders (emoMonal/behavioral problems, sex,

maternal educaMon, maternal prenatal smoking) •  negated the effect of cigarene smoking •  Cannabis use (EA and LA) remained significant predictor of psychosis (aOR

3.7 and 2.97) –  PsychoMc experiences at age 12 did not predict cannabis use later

Jones HJ et al. JAMA Psychiatry 2018.

What does contrast do to the kidneys?

Hinson JS et al. Risk of acute kidney injury a\er intravenous contrast media administra=on. Ann Emerg Med 2017 Jan 19; [e-‐pub]. (h^p://dx.doi.org/10.1016/

j.annemergmed.2016.11.021

What we know: •  There are two other studies that show that CT with contrast does not decrease renal funcMon.

This study: retrospecMve •  7201 who underwent contrast-‐enhanced CT •  5499 who underwent unenhanced CT •  5234 who did not undergo CT (control for other factors that might increase Cr.)

•  Propensity scoring to match groups. •  Inclusion criteria: baseline creaMnine of 0.4–4.0 mg/dL.

Inclusion Criteria •  CreaMnine within 8 hours before CT, repeat within 72 hours aier CT

•  Exclusion: – Dialysis – Transplant – CT within 6 months before the study

Outcome measures •  Cr increase =/> 0.5mg/dl •  Or 25% over baseline

No difference in renal outcomes. So don’t go hog wild but it is OK to do a CT with contrast if necessary in folks

with Cr<4.0mg/dl We also now have a meta-‐analysis:

Aycock RD et al. Acute kidney injury aier computed tomography: A meta-‐analysis. Ann Emerg Med 2017Aug 12;

[e-‐pub].

Should we use BNP to guide CHF therapy?

Felker GM et al. Effect of natriure=c pep=de–guided therapy on hospitaliza=on or cardiovascular mortality in high-‐risk pa=ents with heart failure and reduced ejec=on frac=on: A randomized clinical trial. JAMA 2017 Aug 22/29; 318:713.

(h^p://dx.doi.org/10.1001/jama.2017.10565)

Nah…. •  894 paMents with HFrEF, a CHF “event” (admission) within 1 year, an elevated BNP in the last month.

•  Average EF 25%, 90% II-‐III CHF level (preny sick!) •  Randomized to guided therapy or usual therapy. Goal was BNP <1000pg/ml

•  Treated per guidelines (ACE, ARB, Entresto, etc.)

•  Primary combined outcome (death or first HF event), followed average of 15 months

•  Stopped early because no benefit to BNP guided therapy.

•  No difference in primary outcomes (37% in both) •  12% mortality in each group. •  10 vs. 12 visits (fewer in non-‐BNP paMents). •  But… the ulMmate BNP and the use of HF drugs did not differ significantly between the two groups

Smartphone app for neonatal bilirubin screening

•  Six sternal images compared to color calibraMon card •  Sent via internet for machine-‐based algorithm analysis •  CorrelaMon between app-‐derived measurement and TSB 0.91 •  Two decision rules:

Taylor JA et al. Pediatrics 2017

Sensi5vity Specificity

>75%ile on Bhutani nomogram to predict TSB in high-‐risk zone

85% 75%

>=13 mg /dL to predict TSB >=17 mg/dL

100% 76%

Concussion (TBI) consideraMons •  Youth (3-‐7) had increased educaMonal needs through middle school

–  Kingery KM etal. J Dev Behav Pediatr 2017

•  Adolescent concussions (in Swedish registry) associated with higher risk of MS (adjusted OR 1.20 for one, 2.3 for 2 or more TBI), –  Montgomery S et al. Ann Neurol 2017

•  Adolescent girls had higher rates of menstrual dysfuncMon (OR 5.85) over 120 days follow-‐up –  Snook ML et al. JAMA Pediatr 2017

IQ/achievement Parent report behavior/EF

Teacher report behavior/EF

Severe TBI x x x

Moderate TBI x x

Mild TBI x x

One less thing to worry about… •  SystemaMc review of 29 studies of combined OCP, vaginal

ring, emergency contracepMon •  NonRifamycin anMbioMcs (PCN, cephalosporins, quinolones,

tetracyclines, macrolids, TMP/SMX, metronidazole, dapsone, isoniazid/streptomycin) do NOT alter: –  Pregnancy rates (OR 1.0, 95% CI 0.8-‐1.2) –  OvulaMon –  Unscheduled uterine bleeding –  ProgesMn levels

•  Rifamycin anMbioMcs do induce hepaMc enzymes that metabolize HC (use DMP).

Simmons KB et al. Am J Obstet Gynecol 2018 Jan

A1c Targets •  Qaseem A et al. Hemoglobin A1c Targets for Glycemic Control

With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians. Ann Intern Med 2018; doi:10.7326/M17-‐0939. Published online at annals.org on 3/6/18.

Four Guidance Statements 1.  Personalize goals of treatment 2.  Aim for A1c level 7-‐8% in most pts with DM2 3.  Consider de-‐intensifying therapy in DM2 pts

currently at an A1c < 6.5% 4.  Treat to minimize symptoms of hyperglycemia

(rather than treaMng to an A1c target) in pts with < 10 year life-‐expectancy, living in a nursing home or with significant comorbidiMes

7 reviewers reviewed 6 society guidelines and their supporMng evidence

Summary •  There really is no good evidence that Mght glycemic control (<6.5% or 7% A1c) saves lives or reduces the risk of serious diabetes complicaMons in most paMents with DM2

•  There is some evidence that aggressively lowering A1c levels results in harm

•  But what about “pay for performance”?

Some (more) Diabetes Stuff

We already know….

Tight control of diabetes II doesn’t seem to make any difference in sparing renal

funcMon. Navaneethan SD et al. Diabetes control and the risks of ESRD and mortality in pa=ents with CKD. Am J Kidney Dis 2017 Aug; 70:191.

(h^p://dx.doi.org/10.1053/j.ajkd.2016.11.018

•  6165 paMents with chronic kidney disease but NOT ESRD and DM II

•  All on insulin or oral diabetes drugs. •  Followed for 2 years 3 months, •  3% to ESRD, 16% died •  U-‐shaped curve for mortality (<6% or >9%) •  No relaMonship to ESRD…with that in mind…

We know that liragluMde does prevent renal disease (GLP-‐1 agonist) . But how good is it? Is the

mechanism from lowering glucose?

Mann JFE et al. Liraglu=de and renal outcomes in type 2 diabetes. N Engl J Med 2017 Aug 31; 377:839. (h^p://dx.doi.org/

10.1056/NEJMoa1616011

•  9500 DM II, longstanding, •  Most known CV disease followed for 4 years •  Macroalbuminuria, GFR, renal related death, doubling of creaMnineà combined endpoint.

•  IT WAS GREAT: 5.7% vs. 7.2%à reduced combined endpoint!! 😺😺😺

•  Yeah, right. Not so fast.

EssenMally all driven by macroalbuminuria

If GFR 30-‐60, reduced GRF loss….by 2 ml/minute. No benefit if outside of this range.

Mechanism likely isn’t glucose control.

Of course it doesn’t cost you an arm and a leg….just a leg.

6.3 vs. 3.4 cases amputaMon per 1,000 Canagliflozin -‐-‐> Invokana But it saves lives, right?

Canagliflozin •  10,000 paMents with CV disease or mulMple risk factors (so this might not be your average diabeMc).

•  3.5 years and reduced HbA1c by 0.6% versus placebo

•  Combined endpoint: non-‐fatal MI, stroke, CV related death. 4/1000 difference

•  NNT = 250 at $8000.00/yr

What was it driven by? Not much.

Oh, and amputaMons of a lower limb? 6.3 vs. 3.4 Do you want to trade a limb for the possibility of non-‐fatal MI?

Sexual dysfuncMon in women •  727 healthy postmenopausal women (mean age 53) randomized to

–  Oral conjugated EE (oCEE) –  Transdermal estradiol (tE2) –  Placebo

•  4 year follow-‐up •  Female Sexual FuncMon Inventory (FSFI) (arousal, lubricaMon, pain)

Taylor HS et al. JAMA Intern Med 2017

FSFI score arousal lubrica5on pain SHBG

placebo decr decr decr

tE2 P=0.002 P=0.001 P=0.002

oCEE P=0.13 increased

Physical AcMvity and Academic Achievement

•  Meta-‐analysis of 26 studies –  Increasing/enriching PE –  IntegraMng PE into school day curriculum –  Enhancing physical acMvity at recess and aier school

•  Increased 10-‐60 min per day improved skills in: – Math –  Reading –  Composite scores –  Time in on-‐task behavior Alvarez-‐Bueno C et al. Pediatrics 2017

Dec.

Infant UTI…does tx duraMon impact outcomes?

•  What is the opMmal duraMon of treatment for IV anMbioMcs for kids under 60 days?

•  Database review-‐ 46 hospitals, 4000 hospitalizaMons for UTI (2005-‐15) –  short-‐term therapy (<=3 days) – 69% –  longer-‐term therapy (>=4 days) – 31%

•  Rates declined over Mme from 50% to 19%

•  No difference in 30 day readmission rate (1.6 vs 1.5%) –  Higher in girls –  Higher in infants less than 15 days old.

Lewis-‐de Los Angeles WW et al. Pediatrics 2017

C. Difficile •  McDonald LC, Gerding DN et al. Clinical PracMce Guidelines for Clostridium difficile infecMon in Adults and Children: 2017 Update by the InfecMous Disease Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA). Clinical Infec=ous Diseases; 2018 [Epub ahead of print].

Can you use me}ormin in those with cardiac and renal disease? Crowley, et al. Clinical Outcomes of Me}ormin Use in PopulaMons With Chronic Kidney Disease, CongesMve Heart Failure, or Chronic Liver Disease A SystemaMc Review Ann Intern Med. 2017;166:191-‐200. doi:10.7326/M16-‐1901

What we already know: •  The FDA (2016) has changed the package for me}ormin allowing use if CrCl >30

•  Don’t start if <45 CrCl but can conMnue unMl the hit CrCl 30.

•  (hnps://www.fda.gov/downloads/drugs/drugsafety/ucm494140.pdf)

This study •  Looked at: Adults with type 2 diabetes and CKD (with

esMmated glomerular filtraMon rate less than 60 mL/min/1.73 m2), and/or CHF, and/or CLD with hepaMc impairment

•  Compared regimens with and without me}ormin.

•  Studies had to report reported all cause mortality, major adverse cardiovascular events, and other outcomes of interest.

What they found: •  17 total studies, > 33,000 paMents •  PaMents who were on me}ormin had bener outcomes than those not on me}ormin even with CHF, chronic liver disease, renal disease.

Mortality: Renal

Mortality: CHF

Readmission rates also lower.

Caveats: Only 3 studies with liver disease but same outcome.

Most studies moderate quality. Studies observaMonal

None-‐the-‐less: don’t go hog wild but me}ormin seems to reduce

overall mortality.

Extra slides! Only 2 cents each!

A deal if we have ever seen one.

Should we use steroids for acute urMcaria?

Barniol C et al. LevoceMrizine and prednisone are not superior to levoceMrizine alone for the treatment of acute urMcaria: A randomized double-‐blind clinical trial. Ann Emerg Med 2017 May 3; [e-‐pub]. (hnp://dx.doi.org/

10.1016/j.annemergmed.2017.03.006)

What we already know: •  Even 1 week of prednisone is enough to increase infecMous complicaMons, thromboembolic disease as well as falls and fractures (probably subclinical myopathy)

•  Waljee AK, Rogers MA, Lin P, et al. Short term use of oral corMcosteroids and related harms among adults in the United States: populaMon based cohort study. BMJ 2017;357:j1415.

This study •  100 paMents with < 24 hours of hives randomized to levoceMrizine 5mg or levoceMrizine + prednisone 40mg X 4 days.

•  Outcome was itch score and relapses

No difference in any outcome. •  No difference of itch score of zero at 2 days (62% vs. 76% favoring placebo).

•  Relapse aier stopping meds 30% vs. 24% (again favoring placebo)

•  Recurrence: 12% vs. 14% (favoring steroids).

UpToDate says to skip the steroids unless there is angioedema. Feel free to use diphenhydramine or hydroxyzine if desired and tolerated.

Does gabapenMn work for back pain?

•  Short answer: Nope! •  Shanthanna H et al. Benefits and safety of gabapenMnoids in chronic low back pain: A systemaMc review and meta-‐analysis of randomized controlled trials. PLOS Medicine;2017. hnps://doi.org/10.1371/journal.pmed.1002369

What did they do? •  Searched for studies gabapenMn and pregabalin used in paMents with chronic low back pain (>3 months duraMon) without radiculopathy.

•  Performed a systemaMc review and meta-‐analysis.

•  Only found 8 trials that met criteria for inclusion. •  Trials were oien small, short-‐duraMon and compared gabapenMnoids to placebo or another analgesic (NSAID, acetaminophen, opioid)

Bonom Line •  What is clinically meaningful? – GabapenMn did show a mean improvement of 0.22 on a 10-‐point pain scale versus placebo

– NNT in other studies = 8 – NNH for various adverse effects range from 6 to 8 – Pregabalin is no bener than other analgesics

CorMcosteroids don’t help in alcoholic hepaMMs (but data quality

is poor) Pavlov CS et al. GlucocorMcosteroids for people with alcoholic hepaMMs. Cochrane Database Syst Rev 2017 Nov 2; 11:CD001511. (hnp://

dx.doi.org/10.1002/14651858.CD001511.pub3)

No more Vitamin D to prevent falls in the elderly.

hnps://www.usprevenMveservicestaskforce.org/Page/Document/drai-‐recommendaMon-‐statement/falls-‐prevenMon-‐in-‐older-‐adults-‐intervenMons1

Is epinephrine safe in the “elderly” when used for anaphylaxis?

Kawano T et al. Epinephrine use in older pa=ents with anaphylaxis: Clinical outcomes and cardiovascular

complica=ons. Resuscita=on 2017 Jan 6; [e-‐pub]. (h^p://dx.doi.org/10.1016/j.resuscita=on.2016.12.020)

•  There is a belief that epinephrine should not be used in the elderly for anaphylaxis because of cardiac risk.

•  Now some data…..

•  492 adults with anaphylaxis in Canadian EDs. •  Respiratory compromise, BP systolic <90, etc. •  What did they find?

“Old” was defined as over 50… •  Epinephrine was used in only 55%!!?? •  67% of those 30-‐39 got epinephrine •  15% of those > 70 got epinephrine

•  Of the adults ge~ng epi, only 5 had cardiac events (mostly non-‐problemaMc, only 1 with a troponin leak). All had IV epi.

•  Overall: Only 1% of those with IM epi had any adverse event vs. 43% with IV.

•  IV was oien overdosed…especially in elderly! 1/31 with IM had adverse events.

•  Use IV only for marked hypotension to avoid unnecessary risk.

How long to you have to treat with NSAIDS in order to increase cardiac risk?

Risk of acute myocardial infarc5on with NSAIDs in real world use: bayesian meta-‐analysis of individual pa5ent

data BMJ 2017; 357 doi: hnps://doi.org/10.1136/

bmj.j1909 (Published 09 May 2017)

•  Looked at European and Canadian databases for individual level data looking at NSAIDS (COX-‐2 and tradiMonal) and the risk of acute MI.

•  446 763 individuals including 61 460 with acute myocardial infarcMon studied.

•  Over age 65.

•  1-‐7 days (or more) increased odds raMo of myocardial infarcMon – Celecoxib 1.24 (CI 0.9-‐1.82) –  Ibuprofen 1.48 (CI 1.0-‐2.66) – Diclofenac 1.5 (CI 1.06-‐2.33) – Naproxen 1.53 CI (1.07-‐2.33) – Rofecoxib 1.58 (CI 1.07-‐2.17)

How long must you pretreat someone ”allergic” to IV contrast before doing a CT or other study?

Mervak BM et al. Intravenous corMcosteroid premedicaMon administered 5 hours before CT compared with a tradiMonal

13-‐hour oral regimen.Radiology 2017 Jul 26; [e-‐pub].

•  RetrospecMve, non-‐inferiority study of 202 paMents treated with a 5 hour protocol versus 626 with 13 hour protocol.

•  The protocol: – 200 mg of IV hydrocorMsone 5 hours and 1 hour before CT.

– 50 mg of IV diphenhydramine administered 1 hour before CT

•  Looked only at allergic reacMons (not flushing, etc.)

•  No difference in break-‐through allergy (2.1% vs. 2.5% p=0.02 for non-‐inferiority.

•  Upper limit 3.7% of difference between the two •  However, maybe it is like penicillin….none of them are allergic anyway.

Are the sins of the father, well, the grandmother, passed on to the son, well, granddaughter? And it isn’t really the

grandmother’s sin….

Serpeloni F et al. Grandmaternal stress during pregnancy and DNA methylaMon of the third generaMon: An epigenome-‐wide associaMon

study. Transl Psychiatry 2017 Aug 15; 7:e1202. (hnp://dx.doi.org/10.1038/tp.2017.153)

EpigeneMcs: Heritable traits NOT by DNA/RNA

•  Basically, methylaMon/acMvaMon of some porMons of DNA or histone changes.

•  For example: – Stress turns on DM and obesity….there is intergeneraMonal inheritability even though not through DNA.

126

This study •  Looked at 121 Brazilian teenagers (mean age, 14; 54% female) and their maternal grandmothers (mean age, 64)

•  98% of grandmothers exposure to violence during life.

•  49% witnessed or experienced violence during the pregnancy being studied.

•  Looked at genome wide methylaMon. •  Violence in pregnancy associated with findings in granddaughters: – MethylaMon of sites associated with vascular disease

– Sites associated with depression, PTSD – Congenital abnormaliMes

•  Other studies in children –  gestaMonal famine –  prenatal psychosocial stress, – maternal psychiatric disorders

•  Obesity in the mother or psychosocial stress associated with DM and obesity.

•  So adverse psychosocial/physiologic events in the grandmother and mother can have health effects on the child, grandchild.

•  Mitchell C et al. Father loss and child telomere length. Pediatrics 2017 Jul 18; [e-‐pub]. (hnp://dx.doi.org/10.1542/peds.2016-‐3245)

•  Romens SE et al. Associa=ons between early life stress and gene methyla=on in children. Child Dev 2014 Jul 24; [e-‐pub ahead of print]. (h^p://dx.doi.org/10.1111/cdev.12270)

CTA or Stress Test? •  Foy AJ et al. Coronary Computed Tomography Angiography vs FuncMonal Stress TesMng for PaMents With Suspected Coronary Artery Disease: A SystemaMc Review and Meta-‐Analysis. JAMA Intern Med. doi:10.1001/jamainternmed.2017.4772.

• 

About the Study •  13 trials included •  10,315 paMents received coronary CTA •  9,777 paMents underwent stress tesMng •  Followed for a mean of 18 months •  No difference in death or rates of cardiac hospitalizaMon

About the Study •  The CCTA group did have significant differences in: – Rate of MI (0.7% vs 1.1%) – Rate of angiography (11.7% vs 9.1%) –  Rate of revascularizaMon (7.2% vs 4.5%)

Bonom Line •  For chest pain evaluaMon, there is no mortality difference between CCTA and stress tesMng. Doctor’s choice!

•  Caveat: Realize that CCTA may result in unnecessary procedures.

New guidelines for pulmonary nodule follow-‐up (18 categories!). Not going to review this,

just know it exists. MacMahon H et al. Guidelines for management of

incidental pulmonary nodules detected on CT images: From the Fleischner Society 2017. Radiology 2017 Feb

23; [e-‐pub]. (h^p://dx.doi.org/10.1148/radiol.2017161659)

Excessive blood pressure lowering (<120mmHg) increases adverse

outcomes. Böhm M et al. Achieved blood pressure and

cardiovascular outcomes in high-‐risk paMents: Results from ONTARGET and TRANSCEND trials. Lancet 2017 Apr 5; [e-‐pub]. (

hnp://dx.doi.org/10.1016/S0140-‐6736(17)30754-‐7)

•  Pooled data of 31,000 high risk paMents – >55, DM, Hx CVD, end organ injury (kidney)

•  Lowest risk: 120-‐140 systolic, diastolic 70-‐80

•  Risk goes up as a “U” shaped curve

To be complete: essenMally same result.

Eryd SA et al. Blood pressure and complicaMons in individuals with type 2 diabetes and no previous cardiovascular disease: NaMonal populaMon based

cohort study. BMJ 2016 Aug 4; 354:i4070. (hnp://dx.doi.org/10.1136/bmj.i4070)

•  Lower risks for nonfatal acute myocardial infarcMon (MI; hazard raMo, 0.76) and total MI, nonfatal stroke, nonfatal CV disease, total CV disease, and nonfatal coronary heart disease.

•  Higher 5 year mortality

Another(year(goes(by .Another($60,000( drug ..and(thatis ... ·...

Documents

Transcript of Another(year(goes(by .Another($60,000( drug ..and(thatis ... ·...