Primecuts – This Week in the Journals

November 20, 2018

By Brianna Knoll, 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.

Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea [1]
Likely many of us have heard that gonorrhea and other sexual transmitted diseases are on the rise in the United States. For gonorrhea, the incidence has increased nearly 67% over the past five years. With this has also come increased reported resistance to our first line agents, ceftriaxone and azithromycin. This study looked at a new kid on the block, zoliflodacin. Fears surrounding resistance lead to fast track designation from the Food and Drug Administration (FDA) for this study. This unique antibiotic is a spiropyrimidinetrione – say that three times fast – and works to inhibit microbial biosynthesis by blocking the formation of fused circular DNA. This study was a multicenter, randomized, phase 2 trial that compared a single dose of 2g and 3g of zoliflodacin verse a single intramuscular injection of ceftriaxone 500 mg. Results showed that both doses of zoliflodacin were as effective as ceftriaxone for rectal gonorrhea with 100% cure and that 3g was as effective for urethra or cervical gonorrhea at 100% cure. For pharyngeal gonorrhea, neither dose was as effective. For pharyngeal gonorrhea, zoliflodacin 2g showed 67% cure and 3g 78% vs 100% cure for ceftriaxone. Zoliflodacin did not have an increase in severe adverse events, the only one reported being an unrelated gunshot wound. Though ceftriaxone still showed superiority, zoliflodacin seems to be a hopeful alternative for patients with multi-drug-resistant Neisseria gonorrhoeae. Of note, the study did not look at patients with pelvic inflammatory disease or with human immunodeficiency virus on anti-retroviral therapy for fear of drug interactions.
Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism [2]

Data has been gathering surrounding outpatient management as an effective treatment for acute pulmonary embolism (PE). This study was out of Kaiser Permanente with ten emergency rooms as intervention sites and eleven control sites. Over 16-months 1,703 patients with acute PE confirmed on imaging were recruited. A clinical decision support system (CDSS) used the PE severity index to determine who was low risk and could be sent home verse who needed to be admitted. This method had been validated previously in a multitude of studies showing that in low risk PE patients, outpatient treatment with therapeutic anticoagulation did not result in worse 90-day outcomes. [3-5] Outcomes for this study were five-day return for PE related signs, symptoms or interventions and 30-day major hemorrhage, recurrent venous thromboembolism, and all cause-mortality. Notably physicians had to choose to use the CDSS, but the intervention also included education and physician-specific audit and feedback. Of the 881 patients diagnosed with PE at intervention sites and 822 at control sites, adjusted home discharge increased at intervention sites that used the CDSS (17.4% pre- to 28.0% postintervention) while there was not an increase at the control sites (15.1% pre- and 14.5% postintervention). There was also no increase in 5-day return visits or 30-day major adverse outcomes. At the start of this study Kaiser hospitals were already managing many PEs in the outpatient setting, and thus similar practices in other hospitals could actually be more profound.

Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial [6]
Patient’s admitted with acute cardiomyopathy often have improvements in their ejection fractions after starting therapy, begging the question of whether or not we should then stop their heart failure treatment. This study looked at patients with dilated cardiomyopathy, a left ventricular ejection fraction < 40%, absent heart failure symptoms, and current use of heart failure medications. Patients with uncontrolled hypertension with systolic blood pressure > 160 and chronic kidney disease were excluded. Patients randomized to come off treatment underwent supervised, step-wise reduction in treatments over 16 weeks. Every two weeks all patients had measured brain natriuretic peptide and cardiac magnetic resonance imaging to assess function. The study was small with only 25 and 26 patients in each treatment group. Eleven of the 25 weaned off treatment relapsed within 6 months while none of those kept on treatment relapsed. No deaths or unplanned admissions occurred in either group. Interestingly, the study then allowed the control group to taper off treatment. In the end, of the 51 original patients only 25 remained off treatment after 6 months. Thus, for now it seems despite return in cardiac functioning, we should keep heart failure patients on their medications indefinitely.

The Physical Activity Guidelines for Americans [7]
This year guidelines surrounding physical activity were updated, the last update being in 2008. A group of 17 academic experts set out to answer 38 questions regarding exercise via a systematic review of over 195 articles.[8] Recommendations were rated strong, moderate, limited or not assignable based on generalizability, quantity and quality of results, and magnitude and precision of effect. Importantly, the recommendation is 150-300 minutes of “unable to talk” or moderate-to-vigorous physical activity a week. Additionally muscle strengthening activity is recommended 2 or more days a week. Notably different from 2008, rather than each exercise activity having to be over a certain amount of time, the group found that any amount of exercise can improve sleep, anxiety, cognition, blood pressure, and insulin sensitivity. Thus, even recommending your patients to take the stairs every day or park a little farther away can make a difference. The group also attempted to address siting during the day but the recommendations are not specific as it really depends how much other exercise your patient is getting – if exercising more, they can sit more and vice-versa. This recommendation does not change much for pregnant, disabled, or elderly patients.

Effect of Exercise Intervention on Functional Decline in Very Elderly Patients During Acute Hospitalization: A Randomized Clinical Trial [9]
Going along my exercise kick, this RCT with 370 hospitalized patients with a mean age of 87.3 randomized patients to physical therapy when needed or usual-care verse 2 daily sessions of resistance, balance, and walking exercises. The group found improvements in functional capacity and cognitive level with planned, daily exercise.

Incidental Pulmonary Nodules Detected on CT Images [10]
Ever wonder what you should do with an incidentaloma on chest imaging? If under 6 mm and not concerned about tuberculosis, there is nothing to do! If 6 to 8 mm, then check on it in 6 months. If over 8 mm then will need to think about additional testing.

Reduced Salt Intake for Heart Failure [11]
This study looked at 9 RCTs involving about 479 patients and found no high-quality evidence that reduced salt intake for heart failure improved mortality, decreased hospitalization, or improved NYHA functional class.

Dr. Brianna Knoll is a resident physician at NYU Langone Health

Peer reviewed by Scott Statman, MD, chief resident, NYU Langone Health

Image courtesy of Wikimedia Commons


1. Taylor SN, Marrazzo J, Batteiger BE, Hook EW, 3rd, Sena AC, Long J, Wierzbicki MR, Kwak H, Johnson SM, Lawrence K et al: Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea. The New England journal of medicine 2018, 379(19):1835-1845.

2. Vinson DR, Mark DG, Chettipally UK, Huang J, Rauchwerger AS, Reed ME, Lin JS, Kene MV, Wang DH, Sax DR et al: Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial. Ann Intern Med 2018.

3. Bledsoe JR, Woller SC, Stevens SM, Aston V, Patten R, Allen T, Horne BD, Dong L, Lloyd J, Snow G et al: Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study. Chest 2018, 154(2):249-256.

4. Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, Renaud B, Verhamme P, Stone RA, Legall C et al: Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet 2011, 378(9785):41-48.

5. Vinson DR, Zehtabchi S, Yealy DM: Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med 2012, 60(5):651-662 e654.

6. Halliday B, Lota, AS, Khalique, Z. et al.: Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial,. Lancet 2018.

7. Piercy K, Troiano, RP, Ballard, RM et al.: The Physical Activity Guidelines for Americans. JAMA 2018.

8. Committee PAGA: 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: US Department of Health and Human Services 2018.

9. Martínez-Velilla N, Casas-Herrero, A, Zambom-Ferraresi, F, et al.: Effect of Exercise Intervention on Functional Decline in Very Elderly Patients During Acute Hospitalization: A Randomized Clinical Trial. JAMA Intern Med Published online November 12, 2018.

10. Anderson I, & Davis, AM: Incidental Pulmonary Nodules Detected on CT Images. JAMA Published online November 8, 2018.

11. Mahtani K, Heneghan, C, Onakpoya, I, et al.: Reduced Salt Intake for Heart Failure: A Systematic Review. JAMA Intern Med Published online November 5, 2018.