A cloroquina e o paraquedas: uma fábula da era COVID19

O cenário atual da COVID-19 tem gerado muitas angústias. É natural que a sociedade anseie por respostas rápidas. Entretanto, o conhecimento gerado por estudos científicos demanda alto investimento, rigidez metodológica e árduo trabalho para que dados coletados sejam confiáveis e gerem resultados robustos e, assim, possam ser aplicados diretamente à população adoecida. Passos científicos importantes têm sido “pulados” para se tentar dar celeridade às respostas exigidas pelo momento atual. De forma mais preocupante, estudos de baixa qualidade metodológica estão sendo publicados e conclusões inapropriadas têm ganhado as páginas dos jornais e posts pouco racionais nas mídias. Baseado em heurística, preceitos científicos e nos dados até aqui divulgados sobre cloroquina e hidroxicloroquina, este texto trata de forma narrativa, metafórica e algo sarcástica o tema através de uma fábula aplicável ao cenário atual, traçando um paralelo liberal entre o paradigma do paraquedas e as recomendações de hidroxicloroquina para tratamento da COVID-19

Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE)

Background: The aging population is associated with increased multimorbidity and polypharmacy. Older adults are at a higher risk of adverse events and reduced therapeutic response. This phenomenon is partially explained by drug interactions and treatment adherence. Most randomized clinical trials have found no significant differences between morning and evening levothyroxine (LT4) administration in young adults, but there is little evidence regarding alternative LT4 regimens in older populations. Thus, the MONIALE trial aims to test an alternative schedule for LT4 administration in older adults. Methods/design: This randomized crossover clinical trial will include participants aged 60 years or older with primary hypothyroidism. The trial groups will consist of morning LT4 intake (60 min before breakfast) or evening LT4 intake (60 min after supper). The primary outcome will be variation in serum thyrotropin (TSH) levels after 24 weeks of the LT4 protocol. The secondary outcomes will be the prevalence of drugs that potentially interact with LT4 and hypothyroidism control according to interaction status. The sample size was calculated to detect a minimum mean difference of 1 mUI/L in serum TSH level between the groups with 80% power and a 5% probability of type I error, resulting in 91 patients per group. The project was approved by the Hospital de Clínicas de Porto Alegre Ethics Committee. Discussion: Considering the aging population, the increased prevalence of multimorbidity and polypharmacy, as well as potential drug interactions and treatment adherence difficulties, an alternative LT4 protocol could be useful for hypothyroidism treatment in the elderly. Prior studies comparing alternative LT4 administration protocols have mainly included young adult populations and have not addressed potential drug interactions

Effects of physical exercise programs on sarcopenia management, dynapenia, and physical performance in the elderly : a systematic review of randomized clinical trials

Introduction. Sarcopenia is a prevalent condition in the elderly population, imposing a significant impact over their functional ability as well as their quality of life. Furthermore, it is associated with greater incidence of major geriatric outcomes, as reduced mobility, falls, loss of independence, cognitive impairment, and all-cause mortality. Physical Exercise Programs directed to improve muscle mass and its function may be key to reduce sarcopenia consequences. However, a significant heterogeneity is found in clinical trials, especially as a consequence of different exercise protocols applied to research subjects. Objectives. To access the effects of physical exercise programs compared to no exercise interventions to improve sarcopenia components and its determinants in sarcopenic elder individuals. Methods. A systematic review was conducted in the Pubmed database to identify randomized clinical trials (RCTs) which tested the effects of physical exercise programs to manage sarcopenia components in sarcopenic elder individuals. Two independent reviewers assessed the studies’ eligibility according to specified inclusion criteria in a four-step strategy. Data regarding population characteristics, muscle mass, muscle quality, muscle strength, and muscle function were extracted from each one of the included studies. Assessment of quality and individual studies risk of bias were assessed through Cochrane Risk of Bias Tool®. Assuming theoretical expected heterogeneity among studies, especially regarding different physical exercise programs and different outcome measurements, authors decided to be conservative and present study results in descriptive tables. Results. Search strategy retrieved 298 papers on PubMed database. )ree more were identified through manual search, being 301 studies revised for inclusion. 278 were excluded during title/abstract review. After further evaluation of 23 fulltexts, 5 RCTs were included. All 5 trials tested the efficacy of isolated exercise programs to improve sarcopenia components in the elderly compared to no physical intervention. Resistance training was the main intervention component in all included trials compared to inactive control groups (health education mainly). Physical training improved muscle strength, muscle quality, and muscle function compared to inactive control groups. Considering muscle mass, no differences were demonstrated. Data metaanalysis was not possible to be performed due to high heterogeneity among trials and small number of studies for each outcome comparison. Conclusion. Heterogeneity among trials and small number of RCTs limited robust conclusions and data metaanalysis. However, resistance training protocols can improve muscle strength and physical performance in elders previously diagnosed with sarcopenia, although its effect size and clinical impact are barely relevant

Evaluation of bedtime vs. morning levothyroxine intake to control hypothyroidism in older patients : a pragmatic crossover randomized clinical trial

Introduction: Drug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating Lthyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients. Materials and Methods: A randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60min before breakfast) or bedtime LT4 intake (60min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen. Results: A total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107. Discussion: Thyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime)