1.
Randomized Trial of Hyperimmune Globulin for Congenital CMV Infection - 2-Year Outcomes
Hughes, B. L., Clifton, R. G., Rouse, D. J., Saade, G. R., Dinsmoor, M. J., Reddy, U. M., Pass, R., Allard, D., Mallett, G., MacPherson, C., et al
The New England journal of medicine. 2023;389(19):1822-1824
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Editor's Choice
PICO Summary
Population
Pregnant women with primary maternal cytomegalovirus (CMV) infection (n= 399).
Intervention
Monthly infusions of CMV hyperimmune globulin until delivery (n= 206).
Comparison
Placebo (n= 193).
Outcome
This planned 2-year follow-up study involved the children of the enrolled women to evaluate whether CMV hyperimmune globulin improves childhood outcomes. Partial data on 2-year outcomes were available for 360 children (90%). Death or CMV infection with severe disability occurred in 20 of the 149 children (13.4%) in the hyperimmune globulin group and in 15 of the 149 children (10.1%) in the placebo group (relative risk, 1.33; 95% confidence interval [0.71, 2.50]. No material differences were found between the groups in the incidence of any component of the composite outcome or in any other outcome at 24 months, including severe disability with or without congenital CMV infection. No deaths occurred after the delivery hospitalization.
2.
Clinical Efficacy of Early Administration of Human Immunoglobulin on Children with Severe Hand-foot-mouth Disease
Wu H, Li L
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2023;33(2):234-236
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Editor's Choice
Abstract
The objective of this study was to investigate the clinical effect of early administration of human immunoglobulin in children with severe hand, foot and mouth disease (HFMD) and its influence on serum c-reactive protein (CRP), creatine kinase (CK), and creatine kinase isoenzyme (CK-MB). One hundred and forty children with severe HFMD were randomly divided into Group A (n=70) and Group B (n=70) according to the random number table method. Group A was treated with routine treatment. Group B was treated with routine treatment, and an early intravenous injection of human immunoglobulin. Serum CRP, CK, and CK-MB in Group B were lower than those in Group A after treatment (all p <0.001). The total clinical effective rate of Group B was 92.9%, which was higher than that of Group A (80.0%, p=0.026). Early administration of human immunoglobulin may reduce the levels of serum markers CRP, CK, and CK-MB in children with severe HFMD. Key Words: Human immunoglobulin, Children, HFMD (Hand, foot and mouth disease).
PICO Summary
Population
Children with severe hand, foot and mouth disease (n= 140).
Intervention
Routine treatment + early intravenous injection of human immunoglobulin (n= 70).
Comparison
Routine treatment (n= 70).
Outcome
Serum c-reactive protein, creatine kinase, and creatine kinase isoenzyme in children who received routine treatment were lower than those who received the routine treatment + human immunoglobulin after treatment. The total clinical effective rate of routine treatment + human immunoglobulin was 92.9%, which was higher than that of routine treatment (80.0%).
3.
Efficacy of convalescent plasma for the treatment of severe influenza
Xu Z, Zhou J, Huang Y, Liu X, Xu Y, Chen S, Liu D, Lin Z, Liu X, Li Y
Crit Care. 2020;24(1):469
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Free full text
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Editor's Choice
Abstract
BACKGROUND Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. METHODS We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. RESULTS A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51-2·23; P = 0.87; I(2) = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. CONCLUSIONS The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.
PICO Summary
Population
Patients hospitalized with severe influenza (5 studies, n= 598).
Intervention
Convalescent plasma or hyperimmune intravenous immunoglobulin (H-IVIG).
Comparison
Various comparators (normal intravenous immunoglobulin, standard care, low-titre anti-influenza, placebo).
Outcome
Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality, number of days in the intensive care unit, or number of days on mechanical ventilation.
4.
Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial
Davey RT Jr, Fernandez-Cruz E, Markowitz N, Pett S, Babiker AG, Wentworth D, Khurana S, Engen N, Gordin F, Jain MK, et al
The Lancet. Respiratory medicine. 2019
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Free full text
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Editor's Choice
Abstract
BACKGROUND Since 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. METHODS This 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. FINDINGS 313 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 primary outcome, the OR in patients with influenza A was 0.94 (0.55-1.59) and was 3.19 (1.21-8.42) for those with influenza B (interaction p=0.023). Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1.06, 95% CI 0.70-1.60; p=0.79). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment. INTERPRETATION When administered alongside standard care (most commonly oseltamivir), hIVIG was not superior to placebo for adults hospitalised with influenza infection. By contrast with our prespecified subgroup hypothesis that hIVIG would result in more favourable responses in patients with influenza A than B, we found the opposite effect. The clinical benefit of hIVIG for patients with influenza B is supported by antibody affinity analyses, but confirmation is warranted. FUNDING NIAID and NIH. Partial support was provided by the Medical Research Council (MRC_UU_12023/23) and the Danish National Research Foundation.
PICO Summary
Population
Hospitalised adults with laboratory-confirmed influenza A or B infection (n= 308).
Intervention
Single 500-mL infusion of high-titre hIVIG (0.25 g/kg bodyweight, 24.75 g maximum (hIVIG group, n=156).
Comparison
Saline placebo (placebo group, n=152).
Outcome
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). In subgroup analyses for the primary outcome, the OR in patients with influenza A was 0.94 and was 3.19 for those with influenza B. Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1.06). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment.