Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

The Evaluation of Cystosonography accuracy in diagnosis of Vesicoureteral Reflux in children

Background: Vesicoureteral reflux (VUR) affects approximately 1% of children. It is a risk factor for acute pyelonephritis. Reflux has been identified in 30-50% of children following urinary tract infection. Reflux nephropathy is one of the causes of hypertension and end stage renal disease in children. The primary diagnostic procedure for evaluation of VUR in children is fluoroscopic voiding cystography (VCUG) and radionuclide cystography (RNC). Many investigators have used voiding urosonography (VUS) for the diagnosis of reflux in an effort to eliminate the radiation exposure especially during follow-up period. Methods: We analyzed 25 children with suspected VUR who underwent RNC and VUS concurrently in Labbafi Nejad Hospital in Tehran. Reflux was diagnosed in 8 patients by RNC and in 9 patients by VUS. One case with reflux in RNC was not detected by VUS, and 2 cases with reflux in VUS were not detected by RNC. Findings: The diagnosis of reflux by these two procedures (RNC and VUS) was comparable (p=0.000, r=0.728). In addition, grades of reflux reported by these procedures were also comparable (p=0.000, r=0.724). We considered RNC as the method of choice for reflux diagnosis. The specifity of VUS was 88% and its sensitivity 87%. Accuracy of this imaging was 88% (PPV=77%, NPV=94%). Conclusions: These results showed that VUS is a valuable procedure in follow-up and screening of patients with vesicoureteral reflux

Evaluation of reinforcement on the mechanical behavior of partially bonded fiber/matrix interface

This paper aims at introducing a new natural composite used as soil stabilizer with particular application in geotechnical engineering. The fibers introduced in the present study could be used as effective soil reinforcement. This research proves the feasibility of the use of modified jute/polypropylene in lime and cement composites and studies their effects on the tensile and compressive strength of the matrix. In general, the optimal mechanical performance of natural composites and durability depends on the optimization of the interfacial bond between natural fiber and matrix. Since the fibers and matrices are chemically different, strong adhesion at their interfaces is needed for an effective transfer of stress and bond distribution throughout an interface. In this paper a theoretical approach for the identification of elastic modulus in composite interfaces is proposed in detail with a reasonable error. The theoretical approach is based on the method using a sum of least squares criterion. The approach is applied through optimization techniques, using analytical sensitivities and correlating adhesion with Young's modulus. The validity and potentiality of the proposed technique is discussed and the results demonstrated the versatility, accuracy, and efficiency of the presented approach. The applied method also appears to be a simple way of predicting the modulus of elasticity in composite interfaces. This leads to a discussion of the most promising stabilization methods for soil reinforcement and the outlook for the future

Low power digital baseband for impulse radio ultra-wideband transceiver

10.1007/s00034-010-9249-6Circuits, Systems, and Signal Processing311223-235CSSP