SummaryBackgroundSince the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.MethodsThis randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.Findings313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the pr...

SummaryThreats of pyrogenicity were discovered more than a century ago. Measures

HIV disproportionately affects racial/ethnic minorities and individuals living in the southern United States, and missed clinic visits account for much of this disparity. We sought to evaluate: (1) predictors of missed initial HIV medical visits, (2) time to initial visit, and (3) the association between initial visit attendance and retention in HIV care. Chart reviews were conducted for 200 consecutive HIV-infected patients (100 in Dallas, 100 in San Antonio) completing case management (CM) intake. Of these, 52 (26%) missed their initial visit, with 22 (11%) never presenting for care. Mean age was 40 years, 85% were men, >70% were of minority race/ethnicity, and 28% had a new HIV diagnosis. Unemployment (OR [95% CI] = 2.33 [1.04-5.24], p = 0.04) and lower attendance of CM visits (OR = 3.08 [1.43-6.66], p = 0.004) were associated with missing the initial medical visit. A shorter time to visit completion was associated with CD4 ≤ 200 (HR 1.90 [1.25-2.88], p = 0.003), Dallas study site (HR = 1.48 [1.03-2.14], p = 0.04), and recent hospitalization (HR = 2.18 [1.38-3.43], p < 0.001). Patients who did not complete their initial medical visit within 90 days of intake were unlikely to engage in care. Initial medical visit attendance was associated with higher proportion of visits attended (p = 0.04) and fewer gaps in care (p = 0.01). Missed medical visits were common among HIV patients initiating or reinitiating care in Texas. Employment and CM involvement predicted initial medical visit attendance, which was associated with retention in care. New, early engagement strategies are needed to decrease missed visits and reduce HIV health disparities.

Background: Spores from basidiomycete fungi (basidiospores) are highly prevalent in the atmosphere of urban and rural settings. Studies have confirmed their potential to affect human health as allergens. Less is known about their potential to serve as stimuli of the innate immune system and induce proinflammatory reactions. Methods: In this study, we evaluated the proinflammatory potential of spores from 11 allergenic basidiomycete species (gilled: Pleurotus ostreatus,Oudemansiella radicata,Armillaria tabescens,Coprinus micaceus,Pluteus cervinus, and Chlorophyllum molybdites, and nongilled: Pisolithus arhizus,Merulius tremellosus,Calvatia cyathiformis,Lycoperdon pyriforme, andBoletus bicolor) based on their potency to induce the release of the proinflammatory cytokine interleukin (IL)-1β in a cryopreserved human whole blood system. In addition, the roles of morphological features of the spores (surface area, shape, and pigmentation) were examined for their role in the IL-1β-including potency of spores. Peripheral blood from healthy volunteers was collected, pooled, and cryopreserved. After stimulating the cryopreserved pooled blood with 10⁶ to 10³ basidiospores/ml, the concentration of IL-1β in culture supernatants was determined with ELISA. Results: Basidiospores manifested concentration-dependent IL-1β-inducing potency, which was more marked among basidiospores from gilled basidiomycetes. At higher concentrations of basidiospores, the IL-1β-inducing potency could be differentiated in the cryopreserved human whole blood system. Morphological features did not correlate with the IL-1β-inducing potency of the basidiospores, suggesting that nonmorphological properties modulate the IL-1β-inducing potency. Conclusion: Our data provide evidence of the proinflammatory potential of basidiospores, and the utility of cryopreserved human whole blood as a human-based in vitro system to study the immune reactivity of allergenic basidiospores.