The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. DATA EXTRACTION AND SYNTHESISIn this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I 2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. MAIN OUTCOMES AND MEASURESThe primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). CONCLUSIONS AND RELEVANCEIn this prospective meta-analysis of clinical trials of patients hosp...

Understanding the consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93% to 75.3%. It also varied per agent, ranging from 48.84-85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N=10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N=4/7, 57.14%) and cardiac disease (N=6/8, 75%), endocrinologic morbidity (N=4/5, 90%), and lower HRQoL (N=4/6, 66.67%). Inadequate compliance with ICT therapy is common. Higher compliance is correlated with the lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.

Introduction: Thalassemia is among the most common genetic disorders globally and many patients suffer from iron overload (IOL) complications that mainly affect the heart, liver and endocrine system. These events may be further complicated by drug-related problems (DRP), an inherent issue among patients with chronic diseases.Objective: The study aimed to evaluate the burden, associated factors and impacts of DRP in transfusion-dependent thalassemia (TDT) patients.Method: Eligible TDT patients under follow-up in a tertiary hospital between 01 March 2020 to 30 April 2021 were interviewed and their medical records were reviewed retrospectively to identify any DRP. DRPs were classified using the Pharmaceutical Care Network Europe (PCNE) classification version 9.1. The incidence and preventability of DRP were assessed and the associated risk factors were estimated by univariate and multivariate logistic regression.Results: A total of 200 patients were enrolled with a median (interquartile range: IQR) age of 28 years at enrolment. Approximately 1 in 2 patients were observed to suffer from thalassemia-related complications. Throughout the study period, 308 DRPs were identified among 150 (75%) participants, with a median DRP per participant of 2.0 (IQR 1.0–3.0). Of the three DRP dimensions, treatment effectiveness was the most common DRP (55.8%) followed by treatment safety (39.6%) and other DRP (4.6%). The median serum ferritin level was statistically higher in patients with DRP compared with patients without DRP (3833.02 vs. 1104.98 μg/L, p &lt; 0.001). Three risk factors were found to be significantly associated with the presence of DRP. Patients with frequent blood transfusion, moderate to high Medication Complexity Index (MRCI) and of Malay ethnicity were associated with higher odds of having a DRP (AOR 4.09, 95% CI: 1.83, 9.15; AOR 4.50, 95% CI: 1.89, 10.75; and AOR 3.26, 95% CI: 1.43, 7.43, respectively).Conclusion: The prevalence of DRP was relatively high amongst TDT patients. Increased medication complexity, more severe form of the disease and Malay patients were more likely to experience DRP. Hence, more viable interventions targeted to these groups of patients should be undertaken to mitigate the risk of DRP and achieve better treatment outcomes.