Efficacy and safety of onasemnogene abeparvovec for the treatment of patients with spinal muscular atrophy type 1: A systematic review with meta-analysis.

BACKGROUND: Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety. OBJECTIVE: Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence. METHODS: This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable. RESULTS: Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated. CONCLUSION: The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain.

Potential and limitations of machine meta-learning (ensemble) methods for predicting COVID-19 mortality in a large inhospital Brazilian dataset.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.

Chagas disease and SARS-CoV-2 coinfection does not lead to worse in-hospital outcomes.

Chagas disease (CD) continues to be a major public health burden in Latina America. Information on the interplay between COVID-19 and CD is lacking. Our aim was to assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients. Consecutive patients with confirmed COVID-19 were included from March to September 2020. Genetic matching for sex, age, hypertension, diabetes mellitus and hospital was performed in a 4:1 ratio. Of the 7018 patients who had confirmed COVID-19, 31 patients with CD and 124 matched controls were included (median age 72 (64-80) years-old, 44.5% were male). At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (p < 0.05). C-reactive protein levels were lower in CD patients compared with the controls (55.5 [35.7, 85.0] vs. 94.3 [50.7, 167.5] mg/dL). In-hospital management, outcomes and complications were similar between the groups. In this large Brazilian COVID-19 Registry, CD patients had a higher prevalence of atrial fibrillation and chronic heart failure compared with non-CD controls, with no differences in-hospital outcomes. The lower C-reactive protein levels in CD patients require further investigation.

[The profile of antimicrobial utilization in a private hospital]. / Perfil da utilização de antimicrobianos em um hospital privado.

The antimicrobials are one of the groups of the most prescribed drugs in hospitals and which cause a great concern for the suitability of their use. The profile of the antimicrobials utilized in a private hospital in the countryside of Rio Grande do Sul State was described and the quantity of each antimicrobial consumed was analyzed. All the prescriptions of patients who utilized antimicrobials while they were hospitalized in the period from March to June 2006 were analyzed. The antimicrobial consumption was expressed in Defined Daily Dose (DDD) in 100 day-beds. The antimicrobial utilization analysis were done generally speaking and divided by age groups and by medical clinics. During the studying period the antimicrobial use prevalence was of 52.4 % (IC 95 % 49.2 - 55.7). The cephalosporins were the most utilized (43.4 %), followed by the penicillins (16.3 %), fluoroquinolones (13.0 %) and aminoglycosides (9.7 %). The high consumption of antimicrobials during the studying period is the result of the absence of a policy for controlling the drugs prescribed in hospital and the lack of protocols of antimicrobial use. In order to exist a control of antimicrobial consumption the hospitals must assume a surveillance policy on the prescriptions of this drug group.

Perfil da utilização de antimicrobianos em um hospital privado / The profile of antimicrobial utilization in a private hospital

Os antimicrobianos são um dos grupos de medicamentos mais prescritos nos hospitais e que causam uma grande preocupação quanto à adequação do seu uso. Descreveu-se o perfil dos antimicrobianos utilizados num hospital privado do interior do Rio Grande do Sul, analisando a quantidade consumida de cada antimicrobiano. Foram analisadas todas as prescrições de pacientes que utilizaram antimicrobianos enquanto internados no período de março a junho de 2006. O consumo dos antimicrobianos foi expresso em dose diária definida (DDD) por 100 leitos-dia. As análises de utilização de antimicrobianos foram feitas em geral e estratificadas por grupos de idade e por clínicas médicas. Durante o período em estudo, a prevalência do uso de antimicrobianos foi de 52,4 por cento (IC95 por cento 49,2-55,7). As cefalosporinas foram as mais utilizadas (43,4 por cento), seguidas das penicilinas (16,3 por cento), fluorquinolonas (13,0 por cento) e aminoglicosídeos (9,7 por cento). O alto consumo de antimicrobianos durante o período em estudo é resultado da ausência de uma política de controle dos medicamentos prescritos no hospital e da falta de protocolos de uso de antimicrobianos. Para que haja um controle do consumo de antimicrobianos, os hospitais devem assumir uma política de vigilância sobre as prescrições deste grupo de medicamentos.

The antimicrobials are one of the groups of the most prescribed drugs in hospitals and which cause a great concern for the suitability of their use. The profile of the antimicrobials utilized in a private hospital in the countryside of Rio Grande do Sul State was described and the quantity of each antimicrobial consumed was analyzed. All the prescriptions of patients who utilized antimicrobials while they were hospitalized in the period from March to June 2006 were analyzed. The antimicrobial consumption was expressed in Defined Daily Dose (DDD) in 100 day-beds. The antimicrobial utilization analysis were done generally speaking and divided by age groups and by medical clinics. During the studying period the antimicrobial use prevalence was of 52.4 percent (IC 95 percent 49.2 - 55.7). The cephalosporins were the most utilized (43.4 percent), followed by the penicillins (16.3 percent), fluoroquinolones (13.0 percent) and aminoglycosides (9.7 percent). The high consumption of antimicrobials during the studying period is the result of the absence of a policy for controlling the drugs prescribed in hospital and the lack of protocols of antimicrobial use. In order to exist a control of antimicrobial consumption the hospitals must assume a surveillance policy on the prescriptions of this drug group.