Primecuts – This Week In The Journals

July 18, 2016


france chateauBy Dana Zalkin, MD 

Peer Reviewed

This week the world witnessed a deadly attack in France, a tumultuous coup attempt in Turkey, and the announcement of the Trump-Pence GOP presidential ticket. As crowds gathered to watch the Bastille Day fireworks display in Nice, France, a massacre ensued when a truck plowed through the crowd killing 84 individuals [1].  While the world attempted to come to terms with what had occurred in France, the presumptive US Republican presidential candidate, Donald Trump, officially announced his running mate in the 2016 presidential election: Gov. Mike Pence of Indiana [2].  And as the policies and political climate of this duo were being analyzed around the country, another international crisis erupted as military forces attempted a coup in Turkey [3].

As we mourn the individuals who lost their lives in France, and continue to pray for peace in Turkey and throughout the world, we turn to acknowledge the most recent advances in medical literature this week.

Ablation versus Escalation of Antiarrhythmic Drugs in Patients with Recurrent Ventricular Tachycardia 

Myocardial infarction often results in scarring, which carries a significant risk of ventricular tachycardia (VT) and subsequent death. Implantable cardioverter-defibrillators (ICDs) have been shown to significantly reduce this risk.  Although ICDs are effective at terminating ventricular rhythms, recurrent VT and ICD shocks are not without consequence.  Patients with recurrent ventricular tachycardia, may have impairment in the quality of life as well as increased risk of death, heart failure, and hospitalization.  Anti-arrhythmic drug therapy is often required in these individuals, however if ventricular tachycardia continues to occur despite these medications, options include catheter ablation or escalating drug therapy, both of which have been shown to effectively reduce recurrent arrhythmias.

The Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial published this week in NEJM compared catheter ablation versus escalated anti-arrhythmic drug therapy in patients with ischemic cardiomyopathy and an ICD who had recurrent VT despite first-line anti-arrhythmic therapy [4].  This study was a multi-center, open-label, randomized controlled trial where 259 patients were randomized to either escalation of antiarrhythmic therapy or VT ablation.  At 2 years follow-up, patients who underwent catheter ablation had a 10% absolute reduction in composite outcome of death, VT storm, and appropriate ICD shocks, with the difference largely driven by reductions in VT storm and ICD shocks given no significant difference in mortality.  Adverse events were more common and more frequent in the antiarrhythmic escalation group.  Additionally, subgroup analysis demonstrated that in those patients who have VT while taking an antiarrhythmic drug other than amiodarone or no antiarrhythmic therapy, catheter ablation was not superior to treatment with amiodarone.   Another important effect of this study is the recognition that better antiarrhythmic therapies are ultimately necessary for this group of patients. 

Sex Differences in Physician Salary in US Public Medical Schools 

The gender wage gap has been a conversation piece for quite some time. In 1963 the Equal Pay Act was signed into action, and at that time women earned 59 cents on average for every dollar earned by men [5].  In 2010, women earned 77 cents on average for every dollar earned by men.  Although there have clearly been advances in the wage gap over time, the gap still persists.

A recent study published in JAMA Internal Medicine unfortunately demonstrated that the wage gap does not spare the medical profession [6].  Previous studies aimed at studying salary difference between male and female academic physicians have been limited by self-reporting surveys, small sample sizes, or a focus on one specialty or region.  This new study used public salary data about 10,241 physicians in 12 states from 24 public medical schools and accounted for age, experience, faculty rank, specialty, and scientific authorship. Overall, female physicians (n = 3549) had a lower mean unadjusted salary compared to male physicians (n = 6692) with an absolute difference of $51,315 (95% CI $46,330-$56,301) and a persistent difference after multivariable analysis with an absolute difference of $19,878 (95% CI $15,261-$24,495).  Salary differences were seen across various specialties as well as academic rankings and research productivity.  Interestingly, women were less likely to have received Medicare payments, and in those who were receiving payments, the mean amount received was lower for women ($38,409 vs. $52,320; p < 0.001).

This study represents the largest known study of wage differences between male and female academic physicians to date. Although this study publicized the glaring difference between male and female physician salaries, something must be done now that these differences are recognized.  As Dr. Kim Templeton, the president of American Medical Women’s Association, commented in the recent NY Times article covering this issue, “just having it out there isn’t going to fix the problem” [7]. 

Does Procalcitonin Guidance Reduce the Duration of Antibiotic Treatment in Critically Ill Patients? 

Appropriate antibiotic use is a common challenge in hospitalized patients. Recognizing and treating septic patients with antibiotics is of the utmost importance as sepsis remains a major cause of death in critically ill patients, however excessively long antibiotic courses are detrimental given the risk of increasing antibiotic resistance.  Studies have demonstrated that procalcitonin guidance can decrease the duration of antibiotic treatment for patients with bacterial infections, however the safety of these protocols has not yet been fully established. Another limitation is that many of these studies were performed in countries with high baseline utilization of antibiotics.

A recent study published in Lancet Infectious Disease sought to assess the efficacy and safety of procalcitonin-guided antibiotic treatment in a large set of ICU patients in a health-care system with relatively lower baseline antibiotic use [8].  The Stop Antibiotics on Procalcitonin guidance Study (SAPS) was a prospective, multicenter, randomized, open-label intervention trial performed throughout fifteen ICUs in the Netherlands with 1575 participants.  The procalcitonin-guided group was offered non-binding advice to discontinue antibiotics if procalcitonin concentration decreased by 80% of more of its peak value or to 0.5μg/L or lower.  The standard-of-care group followed local antibiotic protocols.  The median duration of treatment was 5 days in the procalcitonin-guided group and 7 days in the standard-of-care group (absolute difference 2.69, 95% CI 0.65-1.78, p < 0.0001) with a significantly lower daily consumption of antibiotics in the procalcitonin-guided group (p<0.0001).  Mortality at 28 days was 20% in the procalcitonin-guided group vs. 25% in the standard-of-care group (absolute difference 5.4%, 95% CI 1.2-9.5, p=0.0122) in an intention-to-treat analysis, and 20% in the procalcitonin-guided group vs. 27% in the standard-of-care group (absolute difference 6.6%, 95% CI 1.3-11.9, p=0.0154) in a per-protocol analysis.  Overall, procalcitonin appears to be a safe and effective tool to reduce antibiotic treatment duration and utilization in ICU patients with bacterial infections, however it must also be noted that this is a tool to aid and supplement rather than replace physician judgment. 

Does Suppressive Antiretroviral Therapy Prevent Within-Couple HIV Transmission During Periods of Sex Without Condoms? 

HIV transmission amongst heterosexual serodifferent couples has been shown to be significantly reduced in HIV-positive adults randomized to early antiretroviral therapy (ART). However, these studies are limited in that they do not consider transmission rates for anal sex, and they report transmission data in the context of consistent condom use, which also prevents transmission.

The PARTNER (Partners of People on ART- A New Evaluation of the Risks) study was an observational multicenter study of serodifferent couples, including heterosexual and men who have sex with men (MSM) partnerships, that have penetrative sex without condoms in which the HIV-positive partner is taking ART and had a suppressed HIV viral load [9]. 1166 HIV serodifferent couples were enrolled with 888 heterosexual (61.7%) and 340 MSM (38.3%) couples.  Phylogenetic analysis was performed if an HIV-negative partner became infected to determine if the transmission was linked to the HIV-positive index partner.  Couples reported condomless sex acts with a median of 37 times per year, with a total of approximately 22,000 condomless sex acts amongst MSM couples and approximately 36,000 amongst heterosexual couples.  Over a median follow-up period of 1.3 years, 11 HIV-negative partners seroconverted.  However, no phylogenetically linked transmissions occurred resulting in a within-couple HIV transmission rate of zero.  Although more data is needed to determine risk estimates over longer periods of time, the PARTNER study has provided new and important data on the effectiveness of ART as a strategy to prevent HIV transmission through condomless sex.

Mini Cuts 

A randomized, double-blind, phase 3 trial published in NEJM this week compared olanzapine with placebo in patients with no prior chemotherapy who were receiving highly emetogenic chemotherapy [10]. Olanzapine significantly improved nausea-prevention and the complete response rate (no emesis and no use of rescue medication) compared with placebo.

Gastroparesis is a complication seen in patients with diabetes. A recent clinical trial in Gastroenterology compared relamorelin  (a pentapeptide-selective agonist of the ghrelin receptor which speeds gastric emptying) versus placebo [11].  Relamorelin significantly reduced vomiting and improved symptoms of impaired gastric emptying.

A study in JAMA Internal Medicine compared quit attempts in patients receiving pictorial warnings versus text-only warnings on cigarette packs [12].  Pictorial warnings increased intentions to quit, forgoing cigarettes, quit attempts, and successful smoking cessation over the 4 week trial period.

Dr. Dana Zalkin is a 2nd year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Jennifer Mulliken, MD, associate editor, Clinical Correlations; chief resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References

[1] Higgins, Andrew. “In Nice, a Vibrant Celebration Gives Way to a Trail of Death.” The New York Times. The New York Times, 14 July 2016. Web. 17 July 2016. http://www.nytimes.com/2016/07/15/world/europe/nice-bastille-day.html?_r=0

[2] Burns, Alexander, and Maggie Haberman. “How Donald Trump Finally Settled on Mike Pence.” The New York Times. The New York Times, 15 July 2016. Web. 17 July 2016. http://www.nytimes.com/2016/07/16/us/politics/mike-pence-donald-trump-vice-president.html

[3] Arango, Tim. “Turkey Detains Thousands in Military in Bid to Regain Control.” The New York Times. The New York Times, 16 July 2016. Web. 17 July 2016. http://www.aina.org/news/20160716111811.htm

[4] Sapp JL, Wells GA, Parkash R, et al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med.2016 Jul 14;375(2):111-21. http://www.ncbi.nlm.nih.gov/pubmed/27149033

[5] “Pay Equity Information.” Pay Equity Information. National Committee on Pay Equity, Sept. 2015. Web. 17 July 2016. <http://www.pay-equity.org/info-time.html>.

[6] Jena AB, Olenski AR, Blumenthal DM. Sex Differences in Physician Salary in US Public Medical Schools. JAMA Intern Med. 2016 Jul 11.

[7] Louis, Catherine Saint. “Dr. Paid Less: An Old Title Still Fits Female Physicians.” The New York Times. The New York Times, 11 July 2016. Web. 17 July 2016. http://www.nytimes.com/2016/07/12/health/women-doctors-salaries-pay-gap.html

[8] de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016 Jul;16(7):819-27. http://www.rug.nl/research/portal/publications/efficacy-and-safety-of-procalcitonin-guidance-in-reducing-the-duration-of-antibiotic-treatment-in-critically-ill-patients(f7dfa528-6e52-46ca-8964-439e3a5009a7)/export.html

[9] Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. 2016 Jul 12;316(2):171-81. http://www.rug.nl/research/portal/publications/efficacy-and-safety-of-procalcitonin-guidance-in-reducing-the-duration-of-antibiotic-treatment-in-critically-ill-patients(f7dfa528-6e52-46ca-8964-439e3a5009a7)/export.html

[10] Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. http://link.springer.com/chapter/10.1007/978-3-319-27016-6_6

[11] Lembo A, Camilleri M, McCallum R, et al. Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis. Gastroenterology. 2016 Jul;151(1):87-96. http://www.ncbi.nlm.nih.gov/pubmed/27055601

[12] Brewer NT, Hall MG, Noar SM, et al. Effect of Pictorial Cigarette Pack Warnings on Changes in Smoking Behavior: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):905-12. http://archinte.jamanetwork.com/article.aspx?articleid=2526671