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.
 A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. (https://www.nejm.org/doi/full/10.1056/NEJMoa2031304?query=featured_home)
Convalescent Plasma is an antibody-rich product made by obtaining blood donations of patients who have been previously affected by COVID-19. Convalescent plasma has been used for the treatment of infectious diseases for over a century, but has only been clearly demonstrated to be effective in the treatment of Argentine hemorrhagic fever. There have been previously published randomized, open label trials published that have shown an adequate safety profile in patients with COVID-19 but no statistically significant difference has been found in time to hospital discharge, clinical improvement, or mortality [2,3]. This study attempted to more clearly determine the effect of Convalescent plasma by conducting a double-blind, placebo-controlled randomized control trial (PlasmAr) to determine if treatment with convalescent plasma led to improved clinical outcomes at 30 days in severe SARS-CoV-2 Pneumonia.
Patients were assigned in a 2:1 ratio to receive either convalescent plasma or placebo. Patients were included in the trial if they had documented +Sars-COV-2 by reverse transcriptase PCR, radiologically confirmed pneumonia, no previous directives rejecting advanced life support, and at least one of the following severity criteria: oxygen saturation (SaO2) below 93% while at rest breathing room air, a PaO2:FIO2 ratio below 300 mm Hg, or a Sequential Organ Failure Assessment (SOFA) or modified SOFA (mSOFA) score of two or more points above baseline status. Notably, patients were excluded if they were pregnant or lactating, of reproductive age and not using contraception for 30 days after enrollment, allergic to blood components, in multi-organ failure, or requiring mechanical ventilation. The primary outcome at 30-days was measured by using 6 mutually exclusive ordinal categories by using an adapted version of the WHO Clinical Scale, 1- indicated death, 2- invasive ventilatory support, 3 hospitalized with supplemental oxygen requirement, 4- hospitalized without supplemental oxygen requirement, 5-discharged without full return to baseline physical function, and 6- discharged with full return to baseline physical function. Secondary outcomes measured were the clinical status on the ordinal scale at days 7 and 14, the time (in days) to discharge from the hospital, the time (in days) to discharge from the ICU, the time to improvement in at least two categories on the ordinal scale, the time to death, and the time to full functional recovery.
A total of 334 patients were enrolled, 228 received convalescent plasma, and 105 received placebo. In regards to the primary outcome, there was no significant difference noted between the convalescent plasma group and the placebo group in the modified WHO ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P=0.46). For secondary outcomes, there was no statistically significant difference for 30-day mortality, no difference in clinical status on the ordinal scale at day 7 or 14, and no difference in the median time from enrollment to hospital discharge, time of death, or time to clinical improvement of at least 2 categories on the ordinal scale. In conclusion, the use of convalescent plasma did not result in a significant clinical benefit when compared with placebo in patients with severe Covid-19 pneumonia which is consistent with previously published randomized open-label studies. Although the study was limited to those with Severe COVID-19 pneumonia and excluded both milder cases as well as life-threatening cases, the use of convalescent plasma as standard of care in clinical practice should be reexamined in this population with no proven clinical benefit.
 Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis (https://www.acpjournals.org/doi/full/10.7326/M20-6315)
Acute Diverticulitis, defined as painful inflammation of the colonic diverticula without abscess or perforation, is a common condition and often managed in the outpatient setting with antibiotics to help speed the recovery process and reduce risk for further complications (i.e. abscess or perforation). The most common antibiotics prescribed in the outpatient setting are typically metronidazole and a fluoroquinolone or amoxicillin-clavulanate. Recently, the FDA has recommended that Fluoroquinolones be reserved for use when there are no alternative treatment options due to the risk of fluroquinolone adverse effects. This study aimed to compare the effectiveness of metronidazole and fluoroquinolone in combination or amoxicillin-clavulanate alone for the treatment of the first occurrence of outpatient diverticulitis in preventing hospitalization for diverticulitis-related inpatient admission, urgent or elective surgery, ED visits, and risk for subsequent Clostridioides difficile infection.
This was a retrospective-cohort study design that utilized longitudinal data from nationwide population-based claims data on both patients 18-64 with private employer sponsored insurance and those age >65 with Medicare. Patients were included as a cohort of adults at the time of first occurrence of an outpatient diagnostic code for diverticulitis and were excluded if they lacked continuous insurance enrollment for 365 days before and 14 days after their first diagnostic code for outpatient diverticulitis. The groups were then divided into those prescribed metronidazole-with-fluoroquinolone versus those with amoxicillin-clavulanate. The primary outcomes were examined 14 days after the diverticulitis diagnosis date and follow up ended at outcome occurrence, death, disenrollment from study base, or end of the study period.
Analysis of patient characteristics found that age, sex, comorbidities, concomitant medication use, and health care use were similar between treatment groups. In both the private employer sponsored insurance cohort (MarketScan cohort) and the Medicare cohort, there were no differences in between treatment groups in diverticulitis-specific 1-year hospital admission risk, 1-year urgent surgery risk, or 3-year elective surgery risk. However, the findings did differ between the two cohorts with regards to C. diff infection. In the MarketScan cohort, 1-year risk for C. diff infection was 0.3% and similar between treatment groups. In the Medicare cohort, the 1-year risk for C. diff infection was significantly higher for metronidazole-with fluoroquinolone (1.2%) versus amoxicillin–clavulanate (0.6%) (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). This corresponds to a number needed to harm of 167.
In conclusion, in a large nationwide cohort, there were no statistically significant differences between combination metronidazole and fluoroquinolone therapy or amoxicillin-clavulanate monotherapy in diverticulitis specific outcomes. Diverticulitis specific outcomes were defined as 1-year hospitalizations, urgent surgery within 1 year, or elective surgery within 3 years. However, in the cohort of Medicare beneficiaries there was an increased risk of Clostridioides difficile infection. In addition, further analysis showed that metronidazole-with-fluoroquinolone therapy was 7 to 8 times more common as amoxicillin– clavulanate for outpatient diverticulitis treatment. Given that the FDA has recommended that fluoroquinolones be reserved for use for conditions with no alternative treatment options (due to side effects) and amoxicillin-clavulanate is non-inferior, a fluoroquinolone sparing approach to outpatient diverticulitis may help reduce future harm. However, this study is limited by the examining databases for insurance claims and thus there is no way of confirming that once a prescription was filled, how much of it was consumed as prescribed. In addition, patients were categorized into treatment groups on the basis of the first antibiotic prescription filled and there was no further analysis for treatment switches or augmentation with further antibiotics which may alter the results.
 Risk of Progression to Diabetes Among Older Adults with Prediabetes (https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2775594)
Pre-diabetes, defined as a Hemoglobin A1c of 5.7-6.4% or a fasting plasma glucose of 100-125 mg/dL or both, has long been used as a marker for increased risk for development of Diabetes Mellitus. However, the risk of developing diabetes after a diagnosis of Pre-diabetes has not been well studied in older adults. The aim of this study is to characterize the risk of development of diabetes in pre-diabetic older adults in a prospective cohort analysis.
3,412 older adults without diabetes were identified from the Atherosclerosis Risk in Communities Study and contacted semi-annually from 2011 through December 2017 for a total 6.5 year follow up period. Of the 3,412 patients, a total of 1,490 patients (44%) had elevated Hemoglobin A1c (5.7-6.4%), 1,996 (59%) had elevated fasting plasma glucose of 100-125, and 1,004 (29%) patients had both. Among the participants that met criteria for pre-diabetes with an elevated Hemoglobin A1c, 97 (9%) progressed to diabetes, 148 (13%) regressed to normoglycemia (HbA1c, <5.7%), and 207 (19%) died. Similar findings were found in patients with an elevated fasting plasma glucose, 112 (8%) progressed to diabetes, 647 (44%) regressed to normoglycemia, and 236 (16%) died.
In this community-based cohort study, there was a high prevalence of pre-diabetes particularly by the definition of elevated fasting plasma glucose. However, patients were far more likely to actually regress to normoglycemia or die before developing diabetes. This study suggests that pre-diabetes may not be a robust diagnostic entity amongst older adults.
 Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis (https://jamanetwork.com/journals/jama/article-abstract/2776688)
This study examined whether administration of vitamin C, thiamine, and hydrocortisone in adults with sepsis-induced respiratory or cardiovascular dysfunction improved outcomes at 30 days, defined as ventilator and vasopressor free days. This was a multicenter, double blind, randomized trial where patients were randomized to receive 1.5g of vitamin C, 100 mg thiamine (100 mg), 50 mg of hydrocortisone every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. There was no statistically significant difference in ventilator and vasopressor free days in the first 30 days following randomization.
 A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis (https://www.nejm.org/doi/full/10.1056/NEJMoa2022166?query=featured_home)
A randomized, multicenter, open-label, parallel-group trial was conducted among hospitalized patients with decompensated cirrhosis who had a serum albumin less than 30 g/L on enrollment. Eligible participants were randomly assigned to receive 20% human albumin solution for up to 14 days or until discharge vs standard of care at that institution with the primary outcome defined as a new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. Results found that among 777 patients enrolled, there was no statistically significant difference between the standard of care and albumin group for all defined primary outcomes. Furthermore, more serious and life-threatening events occurred in the albumin group.
 Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation (https://jamanetwork.com/journals/jama/article-abstract/2776690)
A randomized, double-blind, placebo controlled trial was conducted that looked at the use of baclofen vs placebo to reduce agitation related events in patients with unhealthy alcohol use disorder who were receiving mechanical ventilation. Results found a statistically significant reduction in agitation-related events (adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]), but also found a statistically significant increase in median length of mechanical ventilation, stay in the ICU. Considering the modest effect and potential adverse events, further research is needed to determine the role of baclofen in this setting.
Dr. Sarah Kayne Allen is a 3rd year resident at NYU Langone Health
Peer reviewed by David Kudlowitz, MD, associate editor, Clinical Correlations
Image courtesy of Wikimedia Commons
 Simonovich, Ventura A., et al. “A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.” New England Journal of Medicine, vol. 384, no. 7, 2021, pp. 619–629., doi:10.1056/nejmoa2031304.
 Li L, Zhang W, Hu Y, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 2020;324:460-470.
 Gharbharan A, Jordans CCE, Geurts van Kessel C, et al. Convalescent plasma for COVID-19: a randomized clinical trial. July 3, 2020 (https://www.medrxiv.org/content/10.1101/2020.07.01.20139857v1.) preprint.
 Gaber, Charles E., et al. “Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis.” Annals of Internal Medicine, 2021, doi:10.7326/m20-6315.
 Rooney, Mary R., et al. “Risk of Progression to Diabetes Among Older Adults With Prediabetes.” JAMA Internal Medicine, 2021, doi:10.1001/jamainternmed.2020.8774.
 Sevransky, Jonathan E., et al. “Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis.” JAMA, vol. 325, no. 8, 2021, p. 742., doi:10.1001/jama.2020.24505.
 China, Louise, et al. “A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis.” New England Journal of Medicine, vol. 384, no. 9, 2021, pp. 808–817., doi:10.1056/nejmoa2022166.
 Vourc’h, Mickael, et al. “Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation.” JAMA, vol. 325, no. 8, 2021, p. 732., doi:10.1001/jama.2021.0658.