SummaryBackgroundInfluenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza.MethodsWe conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480FindingsBetween January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]).InterpretationResults from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.

Background The use of sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia lacks sufficient efficacy data in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD); however, use remains widespread. Recent evidence suggests that this population may be at risk for serious gastrointestinal adverse effects with SPS. Methods. We conducted a single-center retrospective cohort study. Adult patients with CKD Stages 4, 5, or ESRD maintained on renal replacement therapy with serum potassium >5 mEq/L and receipt of SPS were screened for inclusion. Our primary outcome was decrease in potassium within 24 h post-30 g oral SPS suspended in 33% sorbitol. Secondary outcomes included decrease in potassium within 24 h from 15 or 30 g SPS doses and gastrointestinal adverse events. Results Of 596 records, 114 were included for analysis. At the first serum potassium level within 24 h post-30 g oral SPS the median potassium decrease was 0.8 mEq/L [interquartile range (IQR) 0.4–1.1; P < 0.001]. At the first potassium level within 24 h post-15 or 30 g SPS, the median potassium decrease was 0.7 mEq/L (IQR 0.4–1.0; P < 0.001]. Post-SPS potassium levels occurred 14–16 h post-SPS. Gastrointestinal side effects occurred within 30 days of SPS in 5% of patients, although only two cases were classified as possibly associated. Conclusions The use of single-dose SPS monotherapy resulted in a significant decrease in serum potassium levels within 24 h in patients with CKD Stage 4, 5, or ESRD. However, it remains unclear if SPS is associated with an increased risk of gastrointestinal injury in this population.

Background: Additional therapies for hepatic encephalopathy (HE) treatment are warranted. There are data evaluating the use of zinc for HE; however, clinical outcomes, specifically in the United States, are unknown. Objective: To compare 30-day and 1-year all-cause readmission rates in patients with cirrhosis complicated by HE on lactulose and rifaximin to those on lactulose, rifaximin, and zinc. Methods: This retrospective study included patients admitted with documented cirrhosis and home medications of lactulose and rifaximin, with or without zinc. Patients were stratified into 2 groups: those receiving lactulose and rifaximin for HE (control) and those receiving lactulose, rifaximin, and zinc for HE (treatment). The primary outcomes were 30-day and 1-year all-cause readmission rates. Results: One-hundred fifty-seven patients were included (102 in control group, 55 in treatment group). Regarding 30-day and 1-year all-cause readmission rates, there was no difference between the control and treatment groups. Conclusion and Relevance: This is the first study conducted in the United States evaluating zinc for HE treatment. Zinc did not impact 30-day or 1-year all-cause readmission rates. Further studies are warranted to evaluate the potential benefit of zinc for HE, possibly in correlation with Model for End-stage Liver Disease-Sodium (MELD-Na) scores.

Background: Cytomegalovirus (CMV) infection/disease is associated with substantial morbidity and mortality among hematopoietic stem cell transplant (SCT) and solid organ transplant (SOT) recipients. Current anti-CMV therapy is associated with significant side effects, including myelosuppression and renal toxicity. Maribavir (MBV) is a potent and selective orally bioavailable anti-CMV agent. This Phase 2 study (EudraCT 2010-024247-32) assessed safety, tolerability, and anti-CMV activity of pre-emptive MBV versus valganciclovir (VGC) among hematopoietic SCT and SOT recipients. Methods: SCT and SOT recipients aged ≥18 years with 1000-100,000 CMV DNA copies/mL in blood/plasma and no documented CMV organ disease were randomized 1:1:1:1 to receive oral MBV 400, 800, or 1200 mg twice daily (BID), or VGC (Weeks 1-3: 900 mg BID, after Week 3: 900 mg once daily; adjusted for renal function), for up to 12 weeks. Primary safety analysis focused on incidence of treatmentemergent adverse events (TEAEs). Primary efficacy endpoint was proportion of patients with confirmed undetectable plasma CMV DNA within 3 and 6 weeks of treatment ("responders"). Treatment effect estimates were calculated for the pooled MBV group versus VGC and compared statistically; no statistical tests were performed on safety endpoints. Results: Between May 2012 and July 2014, 159/161 randomized patients received study drug (119 MBV [58 SOT], 40 VGC [19 SOT]); median (range) age 58 (18-76) years. Efficacy results are shown in the table.