Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N...

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Update in Hospital Medicine 2017 Elizabeth Burton, MD, CCFP Hospitalist, QE II Health Science Centre, Halifax, NS September 30, 2017

Transcript of Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N...

Page 1: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Update in Hospital Medicine 2017

Elizabeth Burton, MD, CCFP

Hospitalist, QE II Health Science Centre,

Halifax, NS

September 30, 2017

Page 2: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

15th Annual

Canadian Society of Hospital Medicine

Faculty/Presenter Disclosure:

• Faculty: Elizabeth Burton

• No Relationships with commercial interests

Page 3: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Methodology

• Journal search:

• NEJM

• Annals of Internal Medicine

• JAMA/ JAMA Internal Medicine

• BMJ

• Lancet

• The Hospitalist

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Case 1

Ms. GI

• 56 year old female with epigastric pain, nausea,

vomiting with gradual onset over 24 hours. Now

unbearable, 9/10 constant pain. No coffee grind

emesis, no melena

• PMH: Generally well, Obesity, no home meds. No

previous surgery

Page 5: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

• Vitals: Temp 37.5, HR 88, BP 152/88, RR 18, O2 sat 94%RA

• Physical exam:

• Normal cardiorespiratory exam. Tender epigastrium. No edema. No

Stigmata of Liver disease

• Labs:

• WBC 12, Hgb 148, Lipase 2300, ALT 58, AST 44, Bili 10, trop <14, Cr 80,

Urea 11, Electrolytes within normal, CRP 120

• ECG: normal sinus rhythm

• Imaging:

• CXR: no acute abnormality

• Abdo US: no cholecystitis, no biliary tract dilation

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Ms. GI is admitted with acute pancreatitis: NPO, high

rate IVF, parentral pain and nausea control.

• Dietician approaches you the next day and asks

what do want to do with her diet?

A. Continue NPO

B. Feed her

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Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic

Review.

Vaughn VM, et al.

Ann Intern Med. 2017;166(12):883. Epub 2017 May 16.

• Systematic review looking at early (<48 hours) or late (>48 hours) feeding in acute

pancreatitis.

• Outcomes:

• Primary: LOS, mortality, readmission

• Secondary: feeding tolerance, N/V/abdo pain, necrotizing pancreatitis

• Extracted data and rated bias in studies

• Of 1319 citations reviewed:

• 11 RCTs including 948 patients

• 7 trials (3 low risk of bias) mild-moderate pancreatitis

• 4 trials (1 low risk of bias) severe pancreatitis

Page 8: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic

Review.

Vaughn VM, et al.

Ann Intern Med. 2017;166(12):883. Epub 2017 May 16.

• Heterogenous feeding protocols (PO, NG, Nasojejunal)

• No studies showed significant increase in adverse effects or worsening

symptoms, regardless of severity with early feeding

• Mild-moderate pancreatitis:

• 4 studies (including 2 with low risk bias): reduced LOS with early feeding

• 3 studies (including 1 with low risk bias): reduced feeding

intolerance/n/v/abdo pain with early feeding

• Severe pancreatitis:

• 1 study (low risk bias): no difference LOS, mortality, symptoms

Page 9: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

• Conclusions:

• No harm and possible benefit to start feeds within

48 hours of admission for mild-moderate

pancreatitis

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Severity in Pancreatitis

• On admission:

• APACHEII: calculator

• SIRS criteria: at least 2 of:

1) Temp >38.3 or <36,

2) HR >90,

3)RR >20 or PaCO2 <32,

4)WBC >12 or <4 or >10% bands

• At 48 hours:

• Ranson: calculator

• CRP: cut off 150

Page 11: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Ms. GI:

• No SIRS criteria

• Mild acute pancreatitis

• Would consider early feeding within 48 hours of

admission

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Case 2Mr. PE

• 77 year old male presented with “fall” with LOC<1min. No CP,

SOB or Abdo pain. Right knee and leg is swollen and sore.

• PMH: MCI, alcohol use disorder, smoker, ?COPD,

hypertension

• Vitals:

• 88/50>>100/60 post fluid

• HR 115>>105 post fluid

• RR 24

• O2 sat 88% room air

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• Physical Exam

• Normal cardiac/respiratory/abdominal exam. No focal neurologic

finding, mild swelling right lateral knee and lower leg. Good ROM

knee

• Labs

• Cr 76, WBC 11, Hgb 110, lytes within normal, trop <14, ABG: mild

hypoxia

• CXR: normal

• Right knee X-ray: no fracture

• ECG: sinus tachycardia, no ST changes, no heart block

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• Admitting doctor stops BP meds and admits with

Falls NYD, likely related to iatrogenic hypotension,

alcohol use +/- something else

• Question: Is there any other important work-up or

diagnoses you would consider in this gentleman

with syncope?

Page 15: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Prevalence of Pulmonary Embolism among Patients Hospitalized for SyncopePaolo Prandoni, et al, for the PESIT Investigators*

N Engl J Med 2016; 375:1524-1531October 20, 2016DOI: 10.1056/NEJMoa1602172

• 11 Italian hospitals, first episode syncope (regardless if other explanations of

syncope)

• Ruled out if:

1) Negative Wells Score (4 or less) AND

2) Negative D-dimer

• If not ruled out had CT-PE protocol or V/Q scan or autopsy

• N= 560

• Mean age 76

• Transient LOC <1min, not obviously stroke, seizure or head trauma

• 2 academic/9 non-academic hospitals

• Excluded if previous syncope, on anticoagulants or pregnant

Page 16: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

• Ruled out N=330, 58.9%

• Scanned patients N= 230, 41.1%

• PE= 97 patients (61 main pulmonary/lobar artery or perfusion defect

>25%)

• 42.2% of scanned patients

• 17.3% of entire cohort [CI 14.2-20.5%]

• 1 in 6 patients presenting with syncope

• Data by alternate explanation:

• 45/355 (12.7%) with alternative explanation for syncope

• 52/205 (25.4%) with no alternative explanation for syncope

Prevalence of Pulmonary Embolism among Patients Hospitalized for SyncopePaolo Prandoni, et al, for the PESIT Investigators*

N Engl J Med 2016; 375:1524-1531October 20, 2016DOI: 10.1056/NEJMoa1602172

Page 17: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

• Clinical features in patients with PE vs those without PE

• Tachypnea (45.4% vs. 7.1%)

• Tachycardia (33% vs. 16.2%)

• Hypotension (36.1% vs. 22.9%)

• Signs/symptoms DVT (40.2% vs 4.5%)

• Active Cancer (19.6% vs. 9.9%)

• 24.7% had NONE of the above clinical features

• Didn’t include ambulatory care patients

• Within scanned patients (N= 230)

• 135: positive d-dimer only

• 3: high Wells score

• 92: high Wells score and positive d-dimer

Prevalence of Pulmonary Embolism among Patients Hospitalized for SyncopePaolo Prandoni, et al, for the PESIT Investigators*

N Engl J Med 2016; 375:1524-1531October 20, 2016DOI: 10.1056/NEJMoa1602172

Page 18: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Prevalence of Pulmonary Embolism among Patients Hospitalized for SyncopePaolo Prandoni, et al, for the PESIT Investigators*

N Engl J Med 2016; 375:1524-1531October 20, 2016DOI: 10.1056/NEJMoa1602172

• Conclusions:

• Important to consider PE in new, isolated

syncope

• D-dimer use

Page 19: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Back to Mr. PE:

• CT PE protocol confirmed PE

• Started on Dabigatran 150mg po BID

• AND…..

Page 20: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Mr. PE at 0300 few days later:

• Acute onset Hematemesis

• Vitals: HR: 130, BP 60/40, RR 24, T 36.6

Page 21: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

What is your immediate management?

A) Two large bore IVs, Fluid bolus

B) Urgent call to ICU/GI

C) IV Pantoloc and maybe octreotide

D) A new dabigatran reversal agent

E) All of the above

Page 22: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• Idarucizumab

• Monoclonal antibody fragment developed to reverse anticoagulant

effects of dabigatran

• Multicenter, prospective, open label study

• 5g IV Idarucizumab to reverse anticoagulation effects of dabigatran in

patients who had either:

A. Uncontrolled bleeding

B. Required urgent procedure

Page 23: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• >18 years, on dabigatran, bleeding (unstable or need surgery that can not

be delayed >8hours)

• Treatment: 5g IV (two 50ml (2.5g) infusions, no more than 15 min apart)

• Blood work: Diluted thrombin time or ecarin clotting time (correlate linearly

with dabigatran concentration)

• Baseline, after first infusion, between 10-30 min after second infusion and

at 1,2,4,12 and 24 hours

• “Complete reversal” was normal blood work

• Clinical outcomes: extent of bleeding and hemodynamic stability, severity of

bleeding, peri-procedure hemostasis, thrombotic events, death at 90 days

Page 24: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• N= 503 (Group A: 301, Group B: 202)

• Median age 78 years

• Group A: GI Bleeds (45.5%), ICH (32.6%), trauma (25.9%).

• Major or life threatening bleeding in 88%

• Maximum percent reversal 100% [CI 100%-100%] at 4 hrs

• Independent of age, sex, renal function or dabigatran

concentration at baseline

Page 25: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• Group A: median time to hemostasis (when able to determine): 2.5 hours

• Group B: median time to procedure 1.6 hours. Surgical hemostasis: 93.4% normal, mild

5.1%, moderate 1.5%, severe 0%

• Mortality :

• Group A: 13.5 % 30 day, 18.8% 90 day

• Group B: 12.6% 30 day, 18.9% 90 day

• Comparison data with warfarin: ICH 50% 30 day mortality warfarin vs 16.3% in this

study

• Thrombotic events:

• 4.8%within 30 days

• 6.8% within 90 days

Page 26: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• Safety data: 23.3% serious adverse effect but felt to

be mostly worsening of index event or co-existing

conditions. No consistent patterns identified.

Delirium, cardiac arrest, septic shock most common

• Recurrent elevation of clotting time at 12-24 hours

in 114 patients (redistribution of unbound

dabigatran from extravascular to intravascular

compartment). Bleeding in only 10 patients.

Repeat dosage can be given.

Page 27: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.Pollack CV Jr,et al

N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11.

• Patients on Dabigatran annual rates of:

• Life threatening bleeding:1.25-1.5%

• Emergency surgery:1.5%

• Cost

• Factor to consider when counselling

Page 28: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Mr. PE

• Received emergent resuscitation, medications

including Idarucizumab and upper endoscopy

with local treatment of bleeding PUD

• Stabilized and recovered

Page 29: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Case 3Mr.CD

• 78 year old male admitted with fever, cough, increased amount and

purulence of sputum and increasing dyspnea

• PMH: Severe COPD with frequent admissions. Past 12 months on:

amoxicillin, doxycycline, cefuroxime X2

• Temp 38.1, HR 98, BP 120/72, RR 22, 02 sat 84% room air

• WBC 11, Hgb 100, Plt 400, Cr 60, lytes within normal

• CXR: RLL pneumonia

• Levofloxacin, Prednisone, Atrovent/ventolin, DVT prophylactic

Dalteparin, Nicotine Patch

Page 30: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

• Any other medication or supplement you would

want to consider in the management of this patient?

Page 31: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression AnalysisNicole T. Shen, et al. Gastroenterology 2017;152:1889–1900

• Reviews have provided evidence for the efficacy of probiotics for the prevention of CDI, but currently

not recommended on guidelines

• Systematic review of RCTs for use of probiotics and CDI in hospitalized patients receiving Abx

• Search identified 1647:19 studies met criteria, total of 6261 patients,

• Hospitalized patients, >18 years old, oral or IV antibiotics for any reason

• Probiotics: any strain or dose

• Common exclusions: pregnant, immunocompromised, ICU, artificial heart valve, pre-existing GI

disorder

• Incidence CDI

• Probiotics: 1.6% (54 of 3277)

• Controls: 3.9% (115 of 2984)

• Pooled RR of CDI in probiotic users 0.42 [CI: 0.30-0.57]

Page 32: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression AnalysisNicole T. Shen, et al. Gastroenterology 2017;152:1889–1900

• Meta-regression analysis:

• Probiotics more effective if given closer to the first

dose of antibiotics, decrease in efficacy for every day

of delay (P<0.04)

• Probiotics given within 2 days of first antibiotic were

more effective (P = 0.02)

• 2 days or less: RR 0.32 [0.22-0.48]

• >2 days: RR 0.70 [0.40-1.23]

Page 33: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression AnalysisNicole T. Shen, et al. Gastroenterology 2017;152:1889–1900

• Safety: no adverse effects in probiotic group

• Meta-analysis so more studies needed on specific

doses, species and formulations

• Still an “off-label” use of probiotics

Page 34: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Mr. CD

• PAD 6: liquid stool, abdominal pain

• + c difficile

• Vitals: 36.7, HR 92, BP 124/68, RR 16, O2 sats 88% RA

• WBC 16, albumin 24, Cr 70, lytes within normal

Page 35: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

How do want to treat the c.diff?:

A. Metronidazole 500mg po TID

B. Vancomycin 125mg po QID

C. Probiotics

D. More than one answer is correct

Page 36: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

C.diff severity

• Severity considerations:

• Scoring system (severe = 2 points or more)

• 1 point for: Age >60, Temp >38.3 degrees, WBC>15,

Albumin <25

• 2 points for: Pseudomembranes on endoscopy or ICU

• Simplified: WBC>15, albumin <30, Cr> 1.5X normal

• Or “Clinical Judgement”

Page 37: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of

Recurrence and Death in Patients with Clostridium difficile Infection

JAMA Intern Med. 2017;177(4):546-553. doi:10.1001/jamainternmed.2016.9045 Published online February 6, 2017.

• Comparison of recurrence and 30 day mortality in

metronidazole vs vancomycin for c.diff treatment

• Retrospective propensity-matched cohort study VA Jan

2005-Dec 2012

• Mean age 68.8 years, 95.9% males

• 2068 vancomycin treated, matched 8069 metronidazole

treated

• 5452 mild-moderate disease, 3130 severe disease

Page 38: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of

Recurrence and Death in Patients with Clostridium difficile Infection

JAMA Intern Med. 2017;177(4):546-553. doi:10.1001/jamainternmed.2016.9045 Published online February 6, 2017.

• Recurrence:

• mild-moderate: no difference metronidazole vs vancomycin

• Severe: no difference metronidazole vs vancomycin

• 30 day mortality:

• All groups: Reduced mortality with vancomycin (adjusted RR 0.86, 95% CI 0.74-0.98)

• Mild-moderate: no difference metronidazole vs vancomycin

• Severe: Reduced mortality with vancomycin (adjusted RR 0.79, 95% CI 0.65-0.97)

• Conclusion:

• Provides ongoing support that severe CDI should be treated with vancomycin

Page 39: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Mr. CD Conclusion:

• Given age, WBC count, low albumin: you treat

with vancomycin

• You know he’s alive in 30 days because he is re-

admitted again with Functional decline.

Page 40: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Take home points

• Pancreatitis

• Early feeding may reduce LOS in mild-moderate pancreatitis

• Syncope

• 1 in 6 “first syncope” presentations: PE

• New Reversal agent for Dabigatran available

• C.diff:

• Probiotics given to inpatients on antibiotics for any reason may reduce risk of

developing c.diff. The earlier they are given, the more benefit. More studies

needed.

• If severe c.diff, vancomycin reduces all cause mortality better than metronidazole

Page 41: Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Questions?