#106 Hotcakes: Cardiac risk, diabetes, pulmonary embolism, opioid use disorder, neck ties and nose picking?!

July 30, 2018 | By Sarah Phoebe Roberts

Short on time but hungry for knowledge? Curbsiders’ Journal Club gives you the speedy article analysis you crave. We provide brief summaries of recent research and news items in the field of internal medicine, so you can save time and stay on top of the literature. On this episode, we were joined by Kashlak Memorial’s very own Chair of Medicine, Dr. Robert Centor AKA @medrants on Twitter or “Uncle Bob” to the Curbsider Crew. This month’s topics include: estimating atherosclerotic cardiovascular disease risk, whether CT pulmonary angiography (CTPA) effectively rules out pulmonary embolism, discharging low risk patients with pulmonary embolism from the ED, metformin and risk of acidosis in patients with CKD, treating opioid use disorder after a nonfatal overdose, Canagliflozin and renal protection in type 2 diabetes, screening for diabetes among patients below age 40, and the association between nose-picking and staphylococcus. ACP members can claim free CME-MOC at acponline.com/curbsiders (goes live 0900 EST on podcast release date).

Thoughts on the Journal Club series? Article or guest nominations? Compliments or complaints? You can reach us at thecurbsiders@gmail.com. We are also on Facebook, Instagram, and Twitter: @thecurbsiders.

Credits:

• Written by: Christopher J Chiu MD, Sarah Phoebe Roberts MPH
• Producers: Christopher J Chiu MD, Sarah Phoebe Roberts MPH
• Editor: Matthew Watto MD
• Hosts: Christopher J Chiu MD, Stuart Brigham MD, Paul Williams MD, and Matthew Watto MD
• Guest: Robert Centor MD
• Hotcakes! Article Reviews

Yadlowsky S, Hayward RA, Sussman JB, McClelland RL, Min Y, Basu S. Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk. Ann Intern Med. 2018;169:20–29. doi: 10.7326/M17-3011

What’s the clinical question? Who is the patient population?

The 2013 ASCVD score “overestimated 10-year risk by roughly 20% overall, with even higher overestimates among black adults. Nearly 12 million adults who have a 10-year CV risk estimate of 7.5% or greater using PCEs — thus qualifying them for statin therapy — would no longer be considered high risk under newer calculations.”

Strengths?
Complex statistical techniques and validation methods.

Weaknesses?
Validation needs to be done on the suggested revised PCEs before clinical practice can be adjusted.

Bottom line?
This is practice changing and the PCEs will need to have continuous calibration in the future as the populations grows and changes. May need to consider other ways of risk assessment (eg. MESA risk score) until validation is done with updated equations.

See also:
This NEJM Journal Watch post summarizing the article.

Belzile D et al. Outcomes following a negative computed tomography pulmonary angiography according to pulmonary embolism prevalence: a meta‐analysis of the management outcome studies. J Thromb Haemost. June 2018. https://doi.org/10.1111/jth.14021

What’s the clinical question? Who is the patient population?
Does negative CT pulmonary angiography (CTPA) effectively rule out pulmonary embolism in all risk groups?

Strengths?
This was a non-industry funded meta-analysis of 22 prospective studies that examined the negative predictive value (NPV) of CTPA based on the pretest probability of different pooled subgroups <20%, 20-29%, 30-39%, >40%. It included 11,872 participants of whom 7,863 patients had a negative CTPA. No publication bias was detected for the included studies.

Weaknesses?
It used prevalence of pulmonary embolism in each subgroup as a surrogate marker for pretest probability for each subgroup.

Bottom line?
Overall, venous thromboembolism (VTE) occurred in 2.4% of patients with a negative CTPA. VTE occurred in 8.1% of patients with a pretest probability >40% (equivalent of Wells score above 6). We should consider additional testing to rule out VTE in patients at the highest risk. The authors suggest lower extremity doppler US, or CT venography (of the lower extremities) as possible additional tests since most of the VTE events were accounted for by DVT.

See also:
NEJM Journal Watch post discussing this article.

Peacock WF, et al. Emergency Department Discharge of Pulmonary Embolus Patients. Acad Emerg Med, May 14 2018. https://doi.org/10.1111/acem.1345

What’s the clinical question? Who is the patient population?
Can low risk patients with pulmonary embolism (defined as a negative Hestia criteria) be safely discharged from the ED on oral rivaroxaban?

Strengths?
This was a pragmatic study that utilized intention-to-treat analysis. The treating clinician was able to choose any FDA approved therapy for PE in the standard of care arm.

Weaknesses?
This industry funded study failed to meet its predefined enrollment of 150 patients per arm.

Bottom line?
Patients with low risk pulmonary embolism as determined by Hestia score of zero can be safely discharged from the emergency department on rivaroxaban. This underpowered study, though underpowered, found no increased risk of bleeding, recurrent venous thromboembolism, or mortality at 90 days for patients discharged from the ED on rivaroxaban. Not surprisingly, early discharge resulted in a reduced length of stay by more than 28 hours and a median cost reduction of $2,738 ($1,496 versus $4,234) at 30 days after randomization.

See also:
NEJM Journal Watch discussion of this study.

Lazarus B, Wu A, Shin J, et al. Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study. JAMA Intern Med. 2018;178(7):903–910. doi:10.1001/jamainternmed.2018.0292

What’s the clinical question? Who is the patient population?
Looking at the risk of acidosis in patients with CKD. Two large retrospective cohorts of patients with DM2, there was no significant association of incident acidosis with eGFR >30.

Strengths?
Large cohort study over clinically appropriate population

Weaknesses?
Observational study, wide time frame between medication initiation and baseline eGFR measurement.

Bottom line?
Initiation of metformin in eGFR 30-44 may be reasonable as first line therapy. We recommend exercising caution in those susceptible to dehydration or at risk for continued worsening renal function.

Larochelle MR et al. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Ann Intern Med. June 2018. doi: 10.7326/M17-3107

What’s the clinical question? Who is the patient population?
How is medication for opioid use disorder (MOUD) associated with mortality after nonfatal overdose?  Retrospective cohort study using several datasets in Massachusetts. Three type of MOUD where examined including methadone maintenance treatment (MMT), buprenorphine and naltrexone.

Strengths?
This was a large prospective cohort study (17,568 opioid overdose survivors over 12 months after overdose)

Weaknesses?
Limited number of patients who receive naltrexone

Bottom line?
MMT  and buprenorphine were associated with decreased all-cause mortality with adjusted hazard ratios (AHR) of 0.47, and 0.63 respectively. Naltrexone did not have a mortality benefit. This study also showed a gross underuse of MOUD and an alarming rate of prescriptions for opioids and benzodiazepines even in the 12 months after overdose. Evidence that expansion of MOUD to more providers may impact population health as we face the trend of increasing heroin overdoses in the US.

See also:
Sordo L et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017. PMID: 28446428

Perkovic, Vlado et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. The Lancet Diabetes & Endocrinology, Volume 0, Issue 0, June 2018. https://doi.org/10.1016/S2213-8587(18)30141-4

What’s the clinical question? Who is the patient population?
CANVAS Program shows the canagliflozin reduced rates of major adverse cardiac events (MACE) and suggested renal benefit in DM2 patients who were at high risk for cardiovascular disease (CVD). Two double blind, placebo control RCTs were included.  Hgba1c values ranged from 7-10.5%. CANVAS had 3 arms – canaglifozin 100 mg or 300 mg, and placebo. CANVAS-R had 2 arms – canagliflozin 100 mg daily with up-titration to 300 mg or matching placebo.

Strengths?
667 centres in 30 countries.

Weaknesses?
Length of follow-up not long enough for hard renal endpoints.

Bottom line? Canagliflozin associated with renal protection (slower eGFR decline, microalbumin lower) in pt’s with DM2. May need longer dedicated studies to really make these claims.

See also:
Lancet commentary: “Keep Calm and Carry on.”

O’Brien et al. Performance of the 2015 US Preventive Services Task Force Screening Criteria for Prediabetes and Undiagnosed Diabetes. J Gen Intern Med. 2018 Jul;33(7):1100-1108. doi: 10.1007/s11606-018-4436-4.

What’s the clinical question? Who is the patient population?
Recommendation that clinicians screen earlier than 40 years of age for diabetes in those with other risk factors listed in the USPSTF guidelines. The limited criteria (40-70 and overweight/obese) vs Expanded Criteria (family history of DM, history of gestational DM, history of PCOS, non-white race) were studied via cross-sectional analysis.

Strengths?
NHANES is a robust database.

Weaknesses?
Due to nature of the NHANES data, confirmatory diagnosis of dysglycemia (prediabetes or diabetes) with repeat testing could not be done (overestimated prevalence?)

Bottom line?
This study provides good evidence that use of the expanded USPSTF criteria would improve the sensitivity for detecting dysglycemia and might help reduce disparate outcomes for disadvantaged groups.

Wertheim HF et al. Nose picking and nasal carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol. 2006 Aug;27(8):863-7.

What’s the clinical question? Who is the patient population?
Does picking your nose increase your risk for Staphylococcus aureus carriage? This study investigates ENT patients and “Healthy Volunteers” who either identify as nose pickers and correlates this with exam findings consistent with persistent nose picking.

Strengths?
Let’s face it, there aren’t very many articles that cover nose picking and S. aureus, so it’s breaking new ground (or mucosa) so to speak.

Weaknesses?
Requires the participants to be honest. According to a recent non-scientific survey, everyone picks their nose. It is very difficult to find the article for review. (Sorry!)

Bottom line?
Don’t pick your nose!

Chiu Bites

1. Dressed to Kill? Can Neckties Spread Infection? From @theconsultguys , apparently neckties are banned in the UK. No evidence that they increase risk of infection and it is possible that that wearing one will increase a patient’s trust in their doctor.
2. Understanding patient preference for physician attire: a cross-sectional observational study of 10 academic medical centres in the USA (Petrilli CM et al. BMJ Open 2018). Questionnaires at 10 academic hospitals in the USA showed photos of male and female physicians in different forms of attire and the pictured physicians were judged on domains like knowledgeable, trustworthy, caring, approachable and comfortable. Docs wearing white coats in formal attire were highly rated especially for primary care and hospitalists. Scrubs preferred for surgeons and ED docs.

Disclosures: Dr Centor reports no relevant financial disclosures. Dr Chiu reports no relevant financial disclosures. Sarah Roberts reports no relevant financial disclosures. Dr Watto reports no relevant financial disclosures. Dr Williams reports no relevant financial disclosures. Dr Brigham reports no relevant financial disclosures.

Goal: Listeners will keep current with the medical literature and news through rapid summary and critical appraisal by The Curbsiders

Learning objectives:
After listening to this episode listeners will…

1. Understand the evidence for overestimation of ASCVD risk by the 2013 Pooled Cohort Equations.
2. Learn the negative predictive value for CTPA in all risk groups.
3. Recall the evidence the safety in discharging low risk patients with PE from the emergency department.
4. Recall the evidence for the risk of incident acidosis in patients based on eGFR above or below 30 mL/min.
5. Learn how Medications for Opiod Use Disorder can affect mortality after non-fatal overdose.
6. Critically analyze whether canagliflozin is associated with renal protection.
7. Evaluate the evidence to expand the criteria for screening diabetes in those under 40 years old.

Time stamps:

• 00:00 Announcements
• 00:07 Disclaimer
• 00:35 Intro to Curbsiders Journal Club
• 04:11 Dr. Centor’s Pick of the Week
• 06:19 Clinical Implications of the Revised Pooled Cohort Equations
• 12:17 Negative Predictive Value in CTPA for VTE
• 18:41 Can low risk patients with PE be discharged from the ED?
• 25:15 Is Metformin associated with Lactic Acidosis in those with low eGFR?
• 33:17 How does MOUD affect mortality after non-fatal overdose?
• 41:13 Canagliflozin and Renal Protection
• 48:26 Performance of USPSTF screening criteria for diabetes
• 51:35 Stuart on Nose picking
• 55:27 Chiu Bites: Infectious ties and physical attire59:55 Outro

Links from the show:

1. Mr Rogers Neighborhood (DVD) https://amzn.to/2NRiJLr (Prime Video) https://amzn.to/2K1Mbw6
2. Mr Robinson’s Neighborhood (SNL clip)
3. I am Big Bird: The Carroll Spinney Story (Prime Video) https://amzn.to/2OmDEqS