Primecuts – This Week in the Journals

March 27, 2018

By Lauren Yokomizo, MD

Peer Reviewed

One of the most underappreciated aspects of the current opioid epidemic is over prescribing in the elderly. In 2016, one in three patients on Medicare, approximately 14.4 million patients, was prescribed opioids[1]. As part of the federal government’s response to the opioid epidemic, Medicare will no longer pay for long term, high dose opioid prescriptions. The new regulation is expected to take effect April 2nd. The rule has been met with a divided response. Supporters praised it as a step towards reducing addiction. Others, including addiction medicine specialists, are concerned that the rule inserts the government in the patient-doctor relationship and could do harm to patients. Dr. Joanna L. Starrels, an opioid researcher and associate professor at Albert Einstein College of Medicine, said in response to the new regulation, “The decision to taper opioids should be based on whether the benefits for pain and function outweigh the harm for that patient and that takes a lot of clinical judgment. It’s individualized and nuanced. We can’t codify it with an arbitrary threshold.” It remains to be seen how the rule will be enforced and will become clearer with time[2].

Now onto recent news in the medical literature:

iCOMPARE finds lower resident satisfaction but no difference in time spent on patient care with longer hours

The Accreditation Council for Graduate Medical Education’s (ACGME) duty hour restrictions have been hotly contested since their initiation in 2011.  The debate has largely been characterized by a lack of data and fierce opinions on both sides.  Sleep deprivation has been extensively proven to cause more medical errors, but shorter shifts also means more patient handoffs, which are also dangerous.  Some are concerned that the restrictions would result in a “shift mentality” and less educational or patient time. Observational studies, however, have shown no changes in patient mortality or clinical outcomes [2].

On March 10, 2017 the ACGME appeared to reverse their previous policy by extending the permissible work hours for interns from 16 hours to 24 hours.  This was likely based on the results of the FIRST trial (Flexibility in Duty Hour Requirements for Surgical Trainees), which found longer hours (“flexible”) noninferior to the prior duty hours with regard to patient outcomes [3].  This change was made before the results of the iCOMPARE trial, the equivalent cluster-randomized study for internal medicine, had published its findings.

Recently published iCOMPARE data in NEJM found that there was no significant difference in time spent in direct patient care between flexible and standard programs (13.0% in the flexible programs and 11.8% in the standard programs; 95% confidence interval [CI], −0.7 to 3.1; P=0.21) or in the mean percentage of time spent on education.  There was also no significant difference in mean test scores (68.9% for flexible vs. 69.4% for standard programs).  Both groups had high rates of burnout [4].

Interns with longer hours reported significantly greater dissatisfaction with the overall quality of education (odds ratio, 1.67; 95% CI, 1.02 to 2.73), with overall well-being (odds ratio, 2.47; 95% CI, 1.67 to 3.65), and with the effect of the program on their personal lives (e.g., time with family and friends) (odds ratio, 6.11; 95% CI, 3.76 to 9.91).

There was significant variation between programs within the same trial arm, suggesting that variations between institutions may be more significant than the duty hour requirements themselves.  While outcomes data is still pending, should there again be no difference in clinical outcomes, reversing the stricter duty hour requirements may have been premature and come at the cost of intern educational satisfaction and well-being.

Cardiovascular benefits of SGLT-2 inhibitors in a global population

Cardiovascular disease(CVD) is the leading cause of death for patients with type 2 diabetes and yet lowering A1c has failed to reduce patients’ cardiovascular(CV) risk.  Fortunately, an emerging body of evidence has suggested that SGLT-2 inhibitors may help fill this therapeutic gap.  Prior RCTs have shown the efficacy of individual SGLT-2 inhibitors in reducing adverse CV events[5,6], while the CVD-REAL study showed similar associations among SGLT2 inhibitors as a class across a large American and European population[7].

A new retrospective study recently presented at American College of Cardiology Conference, CVD-REAL 2, look at the effect of SGLT-2i compared to other glucose lower drugs (oGLD) on cardiovascular outcomes in an expanded population from Asia-pacific, Middle East, and North America[8]. 400,000 new users of any SGLT-2i or oGLD with and without CVD from South Korea, Japan, Singapore, Australia, Israel, and Canada were identified and included in the trial.  Propensity scores for SGLT-2i initiation were developed and episodes of SGLT-2i and oGLD initiation were matched in a 1:1 ratio. Hazard ratios (HRs) for death, hospitalization for heart failure (HHF), death or HHF, MI and stroke were assessed by country and pooled using weighted meta-analysis.  Use of SGLT-2i vs. oGLD was associated with lower risk of death (HR 0.51, 95%CI 0.37–0.70; P<0.001), rehospitalizations for heart failure (HR 0.64, 95%CI 0.50–0.82; P=0.001), MI (HR 0.81, 95%CI 0.74–0.88; P<0.001) and stroke (HR 0.68, 95%CI 0.55–0.84; P<0.001).  Results were at least directionally consistent across countries and patient subgroups, including those with and without CVD.

In addition to the inherent limits of a retrospective study with multiple statistical adjustments, the study was limited by a short follow-up period, lack of safety data, varying clinical data by country (e.g. only inpatient settings in Japan and Singapore, no comorbidity data from Australia).  Despite these limitations, the overall trend continues to support the CV risk reducing benefits of SLGT-2 inhibitors as a class in for patients with type 2 diabetes.

Surgical left atrial appendage closure for prevention of thromboembolic events

Anticoagulation in elderly patients with atrial fibrillation is often challenging for clinicians.  Recent studies have shown a physician tendency to under prescribe anticoagulation to elderly patients; anecdotally, concerns about falls and bleeding events are commonly cited as reasons for this deviation, as well as issues like cost or compliance.

A retrospective cohort study published in JAMA may offer an alternative solution[9].  Friedman et al used data from Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) and Medicare claims data to explore the relationship between surgical left atrial appendage occlusion (S-LAAO) performed concurrently with cardiac operations and the risk of postoperative thromboembolic complications.  They found 10,524 patients undergoing cardiac procedures, including 3892 patients (37%) who underwent S-LAAO during their operation. At a mean follow-up of 2.6 years, S-LAAO, compared with no S-LAAO, was associated with lower unadjusted rates of readmission for thromboembolism (4.2% vs 6.2%), all-cause mortality (17.3% vs 23.9%), and the composite end point of thromboembolism, hemorrhagic stroke, and all-cause mortality (20.5% vs 28.7%), but no significant difference in rates of hemorrhagic stroke (0.9% vs 0.9%).

The most interesting finding was a subgroup analysis of patients who received only S-LAAO without anticoagulation on discharge that found that they had a significantly lower thromboembolism rate compared with those who received neither S-LAAO nor anticoagulation (sHR, 0.26; 95% CI, 0.17-0.40; P < .001).   Prior studies of LAAO (e.g. via WATCHMAN devices) found a benefit primarily from reduction in bleeding events from anticoagulation rather than a reduction in stroke risk.  This finding suggests that S-LAAO may be an adequate prophylactic treatment of thromboembolism to avoid anticoagulation and its associated complications.

As this was a retrospective observational study, significantly limited by its nonrandomized design (which the authors attempted to counterbalance with IPW statistical analysis), reliance on claims data rather than known clinical outcomes, varying surgical procedures and techniques, and division by discharge medication (without information on duration or adherence to therapy), the most the authors could recommend was further randomized clinical trials to evaluate this further.


A recent study in CHEST found no difference in pathogen, illness severity, or clinical outcome in patients with community acquired pneumonia seen on CT but not chest x-ray to patients with community acquired pneumonia seen on chest x-ray[10].

A case control study recently published in the Annals of Internal medicine found that opioid use is associated with an increased risk of invasive pneumococcal infection[11].

A recently published self-controlled case series of obese patients with COPD a decreased risk of COPD exacerbation after bariatric surgery[12].

Dr. Lauren Yokomizo is a 2nd year internal medicine resident at NYU Langone Health.

Peer reviewed by Ian Henderson, MD, chief resident in internal medicine, NYU Langone Health.

Image courtesy of Wikimedia Commons


  1. Nudelman, Jodi, et al. Opioids in Medicare Part D: Concerns about Extreme Use and Questionable Prescribing. HHS OIG Data Brief. July 2017. OEI-02-17-00250.
  2. Hoffman, Jan. “Medicare Is Cracking Down on Opioids. Doctors Fear Pain Patients Will Suffer.” The New York Times. 27 Mar. 2018. Web. 27 Mar. 2018.
  3. Philibert I, Nasca T, Brigham T, Shapiro J. Duty-hour limits and patient care and resident outcomes: can high-quality studies offer insight into complex relationships? Annu Rev Med 2013;64:467-483
  4. Bilimoria KY, Chung JW, Hedges LV, et al. National cluster-randomized trial of duty-hour flexibility in surgical training. N Engl J Med 2016;374:713-727
  5. Desai SV, Asch DA, Bellini LM, et al. Education outcomes in a duty-hour flexibility trial in internal medicine. N Engl J Med. DOI: 10.1056/NEJMoa1800965.
  6. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med2017;377:644-657
  7. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med2015;373:2117-2128
  8. Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation 2017;136:249-59.
  9. Kosiborod M, Lam CSP, Kohsaka S, et al. Lower Cardiovascular Risk Associated with SGLT-2i in >400,000 Patients: The CVD-REAL 2 Study. J Am Coll Cardiol (in press). DOI: 10.1016/j.jacc.2018.03.009
  10. Friedman et al. “Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery.” JAMA 2018;319(4):365-75.
  11. Upchurch, Cameron P. et al. Community-Acquired Pneumonia Visualized on CT Scans but Not Chest Radiographs CHEST , Volume 153 , Issue 3 , 601 – 610
  12. Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, Mitchel EF, et al. Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case–Control Study. Ann Intern Med. 2018;168:396–404. doi: 10.7326/M17-1907
  13. Goto, Tadahiro et al. Reduced Risk of Acute Exacerbation of COPD After Bariatric Surgery. CHEST , Volume 153 , Issue 3 , 611 – 617