Primecuts – This Week in the Journals

March 21, 2019

By Liz Roca-Nelson, 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.


One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis [1]

Tuberculosis (TB) is the number one cause of death from infectious disease globally.(2) Approximately 1000 daily deaths from TB occur in people co-infected with HIV, including those on antiretrovirals. (1-2) The World Health Organization strongly recommends preventive therapy for latent TB infection in people living with HIV; however, this includes 3-9 months of treatment with isoniazid and/or rifapentine.(3) This poses concerns about adherence to long-term therapy and drug resistance.

A total of 3000 participants were enrolled in this open-label, phase-3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid with 9 months of isoniazid alone in HIV patients living in high TB prevalence areas and/or those with evidence of latent TB infection. The participants were followed for 3 years and the primary end point was a diagnosis of or death from TB. This was only reported in 2% of both groups (rate difference in the 1 month group, -0.02 per 100 person-years; 95% CI, 0.30).

This trial demonstrated the noninferiority of a 1-month rifapentine regimen for the prevention of TB in HIV-infected patients. Furthermore, the percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs 90%, p<0.001). An important limitation, which needs to be addressed in future research, is the cost effectiveness of rifapentine, especially in the lower-income settings where most TB cases occur. However the results of this regimen remain promising, and will potentially be reflected in future guideline updates.

Automated insulin dosing guidance to optimize insulin. Management in patients with type 2 diabetes: a multicenter, randomized controlled trial. [4]

Adequate insulin replacement therapy can help prevent diabetes (DM) complications and reduce healthcare expenses. Despite numerous pharmacologic advances, the average A1C in insulin users in the USA (as in Europe) is approximately 8.5% and a third of users continue to experience A1c >9%.(4-5) This is known as the “insulin paradox,” which is thought to result from intra-individual and inter-individual variation in insulin requirements. This could be tackled with patient education and frequent visits for insulin dosage titration; however, this is time consuming and resource-intensive. The d-Nav is a handheld device which analyzes glucose readings to calculate a suggested insulin dosage, thus helping with insulin titration.

A total of 181 patients were recruited from 3 diabetes centers in the United States and enrolled in this multicenter, randomized, controlled study. Participants were included if they had a hemoglobin A1C (HbA1c) from 7.5 to 11% and had been using the same insulin regimen for 3 months. Participants were randomized to d-Nav plus helathcare professional support versus healthcare professional support alone.   The mean pre-intervention HbA1c was 8.7%, which after 6 months decreased by 1%  in the intervention group and 0.3% in the control group (p < 0.0001), illustrating the efficacy of d-Nav addition.

This is a very promising study, as it showed improvements in HbA1C were three times greater in the intervention group than in the control group. There were also less episodes of hypoglycemia in the intervention group. However, it requires participants to check their glucose level every time before using insulin which may pose a logistical and financial barrier for some patients. This study was conducted over 6-month period and a longer duration is warranted if it were to impact our current guidelines.

Effect of Catheter Ablation vs Antiarrythmic Medication on Quality of Life in Patients With Atrial Fibrillation. The CAPTAF Randomized Clinical Trial. [6]

Atrial fibrillation (AF) is the most common cardiac tachyarrythmia and patients’ symptoms range from debilitating to completely asymptomatic. First-line treatment typically consists of either beta blockers for rate control or antiarrythmic therapy for rhythm control. Catheter ablation is recommended for symptomatic drug-refractory AF, and until now there has been no study which looked at how the procedure impacts quality of life (QoL).

The CAPTAF study was a multicenter randomized trial aimed at evaluating the effect of antiarrythmic pharmacotherapy versus catheter ablation on QoL in patients with symptomatic AF. At total of 155 Scandinavian patients with at least 6 months of symptomatic AF despite antiarrythmics or beta blockers were randomized to catheter ablation (n = 79) versus previously untried antiarrythmic drugs (n = 76). QoL was assessed with the General Health subscale score (GHS) taken at 0 and 12 months. The GHS was 11.9 points in the ablation group compared to 3.1 in the medication group (95% CI, 3.1-14.7; P=0.003), illustrating that the improvement in QoL at 12 months is superior for those who undergo catheter ablation compared to antiarrythmic medication. Although not statistically significant, there was a signal towards decreased AF burden in the catheter ablation group (-12.9% vs 0.7%, p = 0.03).

One of the major limitations is that this study was not blinded and participants’ bias, as well as, placebo effect, may have contributed to symptoms reported. Additionally, AF can cause serious consequences, including death, stroke and even cardiac arrest. Recent trials (including CABANA) demonstrated that catheter ablation is not any better than medical therapy in preventing these consequences(7). However, in the CABANA trial catheter ablation significantly reduced mortality or CV hospitalization by 17% compared to drug therapy. These results, taken with the improved QoL and decreased AF burden seen in the CAPTAF trial, will be important in developing future guidelines regarding the indications for catheter ablation.

Indwelling Pleural Catheters in Hepatic Hydrothorax. A single-Center Series of Outcomes and Complications [8]

Indwelling pleural catheters (IPCs) were approved by the US Food and Drug Administration in January 2017 for management of refractory nonmalignant pleural effusions. Now there is increased interest in their proposed role for the management of hepatic hydrothorax (HH), a debilitating consequence of end-of-stage liver disease. Typically its management consists of sodium restriction, diuretics, serial thoracentesis and liver transplantation if necessary.

This was a retrospective review of 62 patients at a single liver transplant referral center who underwent IPC placement for HH over a 10-year period. The mean MELD-Na score at the time of IPC placement was 24. The majority of patients had also received the typical management outlined above and 21 patients (34%) received peri=procedural antibiotics. In total 33 IPCs (53%) were placed as a bridge to liver transplantation with 10 patients (16%) successfully transplanted.  Of all 62 patients, 22 (36%) developed complications most commonly empyema which was diagnosed in 10 patients (16.1%).

We should not ignore the high number of complications, especially infections noted in this review. Some pleural infections in HH patients are related to the intrathoracic translocation of infected ascites (spontaneous bacterial empyema) and not secondary to IPC insertion. The alternative treatment of repeated thoracentesis is also associated with high complication rates and increased trips to clinic, which may pose a barrier to some patients, especially to those at the end of life. This study reinforces the importance of multidisciplinary discussions at the end of life, and illustrates that IPC can be used for either as a bridge to transplant or palliative care. Fortunately the REDUCE trial (A randomized Controlled Trial Evaluating the Efficacy of Indwelling Pleural Catheters in Persistent Non-Malignant Symptomatic Pleural Effusions) is ongoing in the UK and could offer further evidence for the development of guidelines for non-malignant pleural effusions.


Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. [9]

The RACE7ACWAS (Rate Control versus Electrical Cardioversion Trial 7-Acute Cardioversion versus Wait and See) is a multicenter, randomized, open-label, noninferiority trial, where hemodynamically stable patients who presented to the emergency department with new onset atrial fibrillation (less than 36hrs) were randomly assigned to undergo a wait-and-see approach (rate control with medication) or early cardioversion. The wait-and-see strategy was noninferior to early cardioversion in obtaining sinus rhythm at 4 weeks (−2.9%  95% CI, −8.2 to 2.2; P=0.005 for noninferiority).

Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans. [10]

The CREOLE (Comparison of Three combination Therapies in Lowering Blood Pressure in Black Africans) trial is a single-blind controlled trial randomizing black patients in sub-Saharan Africa to 3 different dual therapy antihypertensive regimens.  Results suggest that in this patient population, a calcium channel blocker (CCB) plus a thiazide diuretic produces more effective blood pressure control than either CCB plus an ACE-inhibitor or a diuretic plus an ACE-inhibitor.

Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized clinical Trial [11]

Approximately, one third of patients receiving maintenance hemodialysis suffer from depression, which can affect quality of life, medication adherence, and potentially health care utilization. The ASCEND (A Trial of Sertraline vs Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression) is the first multicenter, open-label, parallel-group, randomized controlled trial which demonstrated that at 12-weeks patients who received sertraline had modestly better depression scores than those in the cognitive behavior therapy group (effect estimate, −1.84 [CI, −3.54 to −0.13]; P = 0.035).

Dr. Liz Roca-Nelson is a 1st-year resident at Brooklyn-NYU Langone Health

Peer reviewed by Scott Statman, MD, Internal Medicine, NYU School of Medicine

Image courtesy of Wikimedia Commons


  1. Swindells, S, One month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14 ;380(11):1001-1011. DOI: 10.1056/NEJMoa1806808.
  2. Floyd, K. The global tuberculosis epidemic and progress in care, prevention and research: an overview in year 3 of the End TB era. Lancet Respir Med. 2018 Apr;6(4):299-314. DOI: 10.1016/S2213-2600(18)30057-2.
  1. World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO.
  2. Bergenstal, R.M., Automated insulin dosing guidance to optimize insulin. Management in patients with type 2 diabetes: a multicenter, randomized controlled trial. The Lancet. 2019 Feb 22; 393(10176):1138-1148. doi: 10.1016/S0140-6736(19)30368-X
  1. Hodish.I. Insulin therapy for type 2 diabetes- are we there yet? The d-Nav story. Clinical Diabetes and Endocrinology. 2018 Apr 10; 4:8. doi: 10.1186/s40842-018-0056-5. eCollection 2018.
  1. Blomstrom-Lundqvist, C., Effect of Catheter Ablation vs Antiarrythmic Medication on Quality of Life in Patients With Atrial Fibrillation. The CAPTAF Randomized Clinical Trial. JAMA. 2019; 321(11):1059-1068. doi:10.1001/jama.2019.0335.
  2. Douglas, L., Effect of Catheter Ablation vs Antiarrythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation. The CABANA Randomized Clinical Trial. JAMA. Published online March 15, 2019. doi:10.1001/jama.2019.0693.
  3. Kniese, C., Indwelling Pleural Catheters in Hepatic Hydrothorax. A single-Center Series of Outcomes and Complications. CHEST. 2019; 155(2):307-314. doi: 10.1016/j.chest.2018.08.1034.
  4. Pluymaekers, N.A.H.A., Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. N Engl J Med. Published online Mar 18,2019. DOI: 10.1056/NEJMoa1900353.  
  5. Ojji, D.B., Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans. N Engl J Med. Published online Mar 18,2019. DOI: 10.1056/NEJMoa1901113 
  6. Mehrotra, R., Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial. Ann Intern Med. 2019;170(6):369-379. DOI: 10.7326/M18-2229