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...

Women with a history of gestational diabetes mellitus (GDM) are at greater risk for cardiovascular disease (CVD) and type II diabetes mellitus (T2DM). Endothelium- and nitric oxide-dependent dilation are attenuated in the microvasculature of otherwise healthy women with a history of GDM and this reduction is mediated, in part, by increased oxidative stress. However, whether this attenuation also reduces insulin-mediated microvascular responses in these women is unknown. We hypothesized that 1) insulin-mediated vasodilation would be attenuated, and that 2) antioxidant treatment would increase these responses, in women with a history of GDM compared to matched women with a history of healthy pregnancy (HC). Nine HC (32±6 yrs.) and 8 GDM (33±6 yrs.) participated in 1 experimental visit. Three microdialysis fibers were placed in the ventral forearm for the local delivery of lactated Ringer’s (control), 15mM N G-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibition), or 5mM ascorbate (non-specific antioxidant). Following baseline measurements, increasing doses of insulin [10-8 -10-4 M] were added to the site-specific perfusates. Red blood cell flux was measured continuously with laser-Doppler flowmetry, and cutaneous vascular conductance was calculated (CVC=flux/MAP) and standardized to maximum (%CVC max; 28mM SNP + 43°C). Subjects with GDM had attenuated insulin-mediated vasodilation (GDM:16.0 ± 3.0 vs. HC: 31.3 ± 4.7 %CVCmax; p= 0.02) at the control site. L-NAME attenuated insulin-mediated dilation in HC (14.7 ± 3.5 %CVCmax, p=0.004) but not in GDM (12.2 ± 1.9 %CVCmax, p=0.48). Local ascorbate perfusion increased insulin-mediated dilation in GDM (27.6 ± 7.2 %CVCmax; p=0.04) but had no effect in HC (p=0.85). These data suggest that women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and that this attenuation is mediated, in part, by increased oxidative stress. Supported by The UI Fraternal Order of Eagles Diabetes Research Center This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

No abstract

No abstract