Primecuts – This Week in the Journals

May 3, 2019

By Alexandria Imperato, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature.  This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose. 

Effect of Combined b-Lactam/Macrolide Therapy on Mortality According to the Microbial Etiology and Inflammatory Status of Patients With Community-Acquired Pneumonia1

Community-acquired pneumonia is an infection of the lower respiratory tract)  by pathogens commonly existing in the community, such as Streptococcus pneumoniae, Mycoplasma pneumoniae, and Legionella pneumoniae and remains associated with high rates of morbidity and mortality.2 Guidelines recommend treatment with (1) a beta-lactam antibiotic plus a macrolide, (2) beta-lactam plus a fluoroquinolone, or (3) fluoroquinolone monotherapy.

The purpose of this study was to evaluate whether a beta-lactam plus macrolide regimen to treat CAP resulted in decreased 30-day mortality as compared to a fluoroquinolone-based regimen, and, if so, whether the causative etiology of the pneumonia and corresponding degree of systemic inflammation was associated with said mortality benefit. The authors conducted an observational study on a prospective cohort of people with CAP admitted to the Hospital of Barcelona from January 1996-December 2016 (n=1715). Inclusion criteria were adults 18 years of age or older at diagnosis, CAP confirmed by characteristic chest imaging and clinical manifestations, known infectious etiology, and receipt of either beta lactam plus macrolide OR fluoroquinolone monotherapy or with additional beta lactam agent as treatment. Exclusion criteria included prior hospital admission of 48 hours or longer in the preceding two weeks, absence of follow up for 4-6 weeks, severe immunosuppression, or empiric treatment with regimens other than those aforementioned.

After adjusting for confounders, the beta-lactam plus macrolide regimen did not significantly decrease 30-day mortality as compared to a fluoroquinolone-based regimen for the study population overall, but did do so in patients with S. pneumoniae CAP and in those with a high systemic inflammatory response (defined as CRP >15mg/dL).  The greatest mortality benefit was observed in those with both factors present.

Although this study did have certain limitations (such as a relatively small sample size restricted to a single institution), there is a need for similar studies to better elucidate best practices for treating a given condition, particularly when existing treatment guidelines consist of multiple options and limited compelling evidence to select one over the other. While conditions such as CAP, by definition, have certain unifying characteristics, there is almost certainly still a degree of heterogeneity in manifestation (e.g., at the cellular or molecular level) given the varying etiologies of the causative pathogens and the unique characteristics of a given affected patient, and successful evidence-based medicine requires continued refinement of guidelines tailored to best address these differences in an evidence-based fashion to better inform clinical decision making.

  1. Ceccato A, Cilloniz C, Martin-Loeches I. et al. Effect of combined beta-lactam/macrolide therapy on mortality according to the microbial etiology and inflammatory status of patients with community-acquired pneumonia.
  1. Prina E, Ranzani OT, Torres A. Community-acquired pneumonia. Lancet. 2015;386(9998):1097-1108. 

Complications and Outcomes of Temporary Transvenous Pacing: An Analysis of > 360,000 Patients From the National Inpatient Sample3

Temporary transvenous pacing (TTP) is a potentially lifesaving intervention utilized in the setting of bradycardia accompanied by hemodynamic instability. Complications of this procedure include ventricular perforation and pericardial tamponade.4 As the authors of this current study note, the majority of previous studies assessing rates of complications associated with TTP are typically single-center, small, and older; their goal, then, was to conduct a current assessment of trends in use of TTP, incidence of complications, and outcomes of inpatients undergoing TTP by analyzing the National Inpatient Sample (NIS), a database of hospital admissions in the United States that consists of data for approximately 8 million hospitalizations annually from 1000 US hospitals.

The study authors utilized NIS data from 2004-2014 to evaluate trends in TTP utilization, post-procedural pericardial and non-pericardial bleeding, mortality, and top five admitting diagnoses among hospitalizations, with in-hospital mortality and post-procedural cardiac tamponade the primary end points and permanent pacemaker insertion, revascularization using PCI/CABG, length of hospital stay, and total hospital costs as secondary end points.

For a total sample size of 360,223 patients, the study found that overall in-hospital mortality was 14.1% for people requiring TTP placement and procedural complication of pericardial tamponade was rare, occurring in 0.6% of hospitalizations. Pneumothorax occurred in 0.9% of hospitalizations, and non-pericardial bleeding occurred in 2.4% of hospitalizations. The authors noted that rates of TTP-associated pericardial tamponade increased from 3.1 complications per 1000 hospitalizations (95% CI, 1.8-4.5) in 2004 to 8.9 complications per 1000 hospitalizations (95% CI, 6.6-11.1) in 2014. Mortality during hospitalization, including TTP insertion, however, remained constant over time. However, statistical analysis revealed that pericardial tamponade was associated with a fivefold increase in risk for in-hospital death (OR, 5.00 [95% CI, 2.51-9.96]). Female sex, teaching hospital status, and in-hospital cardiac arrest were identified as factors associated with TTP-related pericardial tamponade.

As the variety and complexity of procedural interventions that physicians can offer to patients continues to evolve and advance, studies such as this one to monitor rates of associated mortality and other associated complications is critical. Although, as the study authors note, those requiring TTP placement by definition are high-risk due to their underlying disease state, and many factors associated with untoward outcomes are not modifiable, some factors, such as association of complications with teaching hospital status, are indeed modifiable (e.g., there is likely a component of operator dependency contributing to poorer outcome) and warrant vigilance for their identification and attention towards their amelioration.

  1. Metkus TS, Schulman SP, Marine JE, et al. Complications and outcomes of temporary transvenous pacing: an analysis of >360,000 patients from the National Inpatient Sample. Chest. 2019; 155(4): 749-757
  1. Erol MK, Sevimli S, Ates A. Pericardial tamponade caused by transvenous temporary endocardial pacing. Heart. 2005;91(4):459. 

Coronary Angiography After Cardiac Arrest without ST-Segment Elevation5

It is well-established that current guidelines for the management of people who present with ST-segment elevation myocardial infarction and cardiac arrest recommend immediate coronary angiography with percutaneous  coronary intervention, as such interventions can potentially save oxygen-deprived myocardium, preserve circulatory function, and prevent potentially fatal arrhythmias.5,6 However, the role of immediate coronary angiography is not well-delineated in those who have experienced cardiac arrest but do not have evidence of ST-segment elevation on ECG. This study was a multicenter trial that randomly assigned 552 patients who had experienced cardiac arrest without evidence of STEMI to either undergo immediate coronary angiography or delayed coronary angiography (following neurologic recovery). The primary end point of this study was survival at 90 days; a number of secondary end points were assessed as well, including recurrence of ventricular tachycardia, neurologic status at discharge from intensive care unit, and survival at 90 days with good cerebral performance.

Data analysis showed that at 90 days, 176 of 273 patients (or 64.5%) in the immediate-angiography group, and 178 of 265 (or 67.2%) in the delayed angiography group were alive (OR, 0.89; 95% confidence interval, 0.62-1.27 with p=0.51). Thus, there was no significant difference in overall survival at 90 days between patients who received immediate angiography as compared to patients who received delayed angiography in those presenting with cardiac arrest but without evidence of STEMI.

Studies such as this one are crucial to better informing management decisions with regard to patient care, particularly in populations that are critically ill (i.e., post-cardiac arrest patients) and when the intervention under consideration is resource-intensive and not without its own inherent risks. It can be tempting to extrapolate known data, such as the efficacy of immediate coronary angiography with PCI if indicated in patients who have experienced cardiac arrest and have evidence of STEMI to a seemingly fairly similar population (i.e., people who have also experienced cardiac arrest, albeit with no evidence of STEMI) and subsequently utilize the same intervention in hopes of achieving similar outcomes. However, coronary angiography is resource-intensive and has risks of its own; therefore, it should not be arbitrarily used unless there exists substantial evidence justifying that its utilization will result in clear benefit to the patient. In this particular case, use of coronary angiography does not translate well between two seemingly similar populations, and there is no reason based on currently existing data to expand the indications for coronary angiography to those who have experienced cardiac arrest but do not have evidence of STEMI.

  1. Lemkes JS, Janssens GN, can der Hoeven NW, et al. Coronary angiography after cardiac arrest without ST-segment elevation. New England Journal of Medicine. 2019; 380(15): 1397-1407.
  1. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American Col- lege of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61(4): e78-e140.

Long-Term Weight Loss with Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study7

The Diabetes Prevention Program was a randomized control trial from July 1996-July 2001 that compared the efficacy of intensive lifestyle intervention, metformin, and placebo in the prevention of Type II diabetes among people with elevated glucose levels and were  overweight or obese (n=3234). The DPPOS (Diabetes Prevention Program Outcome Study) represented long-term follow up for DPP participants and commenced in September 2002; it assessed the remaining DPP participants (n=2779) for the incidence of DM and development of diabetes-related complications. While DPPOS is still ongoing, this study analyzed the differences in long-term weight loss maintenance by intervention group from the original DPP study among those participations who achieved weight loss of at least 5% at one year from study initiation and also evaluated factors that predicted maintenance of weight loss for up to 15 years.

This study showed that after one year following study initiation, 28.5% of participants in the metformin group (n=289), 62.6% in the intensive lifestyle intervention group (n=640), and 13.4% in the placebo group (n=137) had lost at least 5% of their baseline body weight. The average weight loss relative to baseline that was maintained between years 6 and 15 post study initiation was 6.2% in the metformin group (95% CI, 5.2%-7.2%), 3.7% in the intensive lifestyle intervention group (95% CI 3.1%-4.4%), and 2.8% in the placebo group (95% CI, 1.3%-4.4%). Independent predictors of long-term weight loss included older age and the amount of weight initially lost.

Studies such as this are important in effectively managing chronic illnesses such as diabetes, where the treatment plan is likely to involve multiple interventions, and to last many years. Not only is it important to know the impact and effectiveness of an intervention in the short term, but knowing the effectiveness of said intervention after a period of time has elapsed is also important because it can help anticipate potential future issues and allow them to be addressed accordingly. For example, this study showed that intensive lifestyle intervention produced the greatest amount of weight loss in the first year, but after 6-15 years, it was really the use of metformin that was associated with maintenance of such weight loss. Therefore, this shows the provider that effective management of DM2 requires both lifestyle changes and pharmacological therapy, as more weight is likely to be lost initially through lifestyle changes, but maintaining weight loss is better associated with use of metformin. Therefore, these interventions complement each other and should be used in combination. Having data from studies such as these allows providers to better effectively manage a chronic health issue in both the shorter and longer term.

  1. Apolzan JW, Venditti EM, Edelstein SL, et al. Long-term weight loss with metformin or lifestyle intervention in the Diabetes Prevention Program Outcomes Study. Annals of internal Medicine. 2019; 1-15


Woolley AE, Singh SK, Goldberg HJ, et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. New England Journal of Medicine. 2019; 380: 1606-1617

A small study (n=44) of people without hepatitis C infection who were organ (heart or lung) recipients from a donor with hepatitis C viremia and in whom an antiviral regimen of 4 weeks’ duration was initiated within hours after transplant showed that this intervention was effective in preventing the establishment of HCV infection in the organ recipient.

Ferrante LE, Pisani MA, Murphy TE, Gahbauer EA, Leo-Summers LS, Gill TM. The association of frailty with post-ICU disability, nursing home admission, and mortality: a longitudinal study. Chest 2018;153:1378–1386.

In this study, the relationship between frailty (defined as ‘a multidimensional syndrome that confers increased vulnerability to adverse accounts’ which becomes more prevalent with increasing age and can be evaluated by a validated scale known as the Fried index, which creates a composite score from criteria that include unintentional weight loss, slow gait speed, low physical activity, muscle weakness, and exhaustion) and post-ICU disability, new nursing home admission, and death was better elucidated. The authors found that frailty prior to ICU admission was associated with post-ICU disability and new nursing home admission among those who survived admission to the ICU, and associated with death among all admissions.

Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. JAMA. 2019;321(15):1466–1480. doi:10.1001/jama.2019.2942

This trial was a randomized clinical trial assessing the efficacy of oral semaglutide  (an oral formulation of a glucagon-like peptide 1 receptor agonist, which have traditionally been administered via subcutaneous injection) versus sitagliptin (DPP-4 inhibitor) as an adjunctive agent to metformin with or without sulfonylurea in people with Type 2 DM. Compared to sitagliptin, oral semaglutide as an adjunctive agent produced significantly greater reductions in hemoglobin A1c values over 26 weeks. The overall proportions of participants experiencing at least one adverse event in the course of treatment was similar across treatment groups.

Dr. Alexandria Imperato is a 1st year resident at NYU Langone Health

Peer reviewed by Kevin Hauck, MD, associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons