The effect of different levothyroxine administration regimens on thyroid hormone levels: a systematic review, pairwise, and network meta-analysis.

INTRODUCTION: This systematic review aimed to compare the effect of alternative levothyroxine administration regimens on thyroid hormone levels and patient-reported outcomes (PROs) among adults with hypothyroidism. METHODS: We searched PubMed, Embase, CENTRAL, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and ICTRP from inception to May/2023 for randomized controlled trials (RCTs). We assessed the risk of bias with Cochrane Risk of Bias 2.0 tool. We analyzed TSH levels by pairwise and network meta-analyses (NMA). The FT4 levels and PROs were qualitatively assessed. RESULTS: We included 14 RCTs (906 participants) comparing different regimens, as bedtime vs. before breakfast. A total of 12 RCTs were at high risk of bias. Seven RCTs were included in the TSH meta-analysis, where the mean difference (MD) and 95% confidence interval (CI) were as follows: bedtime vs before breakfast (4 RCTs) 0.69 (-1.67-3.04), I2 = 92%, very low certainty evidence; weekly dose vs before breakfast (2 RCTs) 1.68 (0.94-2.41), I2 = 0%, low certainty evidence; and at breakfast vs before breakfast (1 RCT) 0.65 (-1.11-2.41), very low certainty evidence. The NMA showed no evidence of differences in TSH level with different regimens. CONCLUSION: The evidence is insufficient to determine the most effective levothyroxine administration regimen for hypothyroidism. SYSTEMATIC REVIEW REGISTRATION: PROSPERO - CRD42021279375.

The sensitivity and specificity of the WHO's ICOPE screening tool, and the prevalence of loss of intrinsic capacity in older adults: A scoping review.

BACKGROUND: The World Health Organization has developed the Integrated Care for Older People (ICOPE) program, a public health strategy to maintain older adults' functional abilities and promote healthier aging. The approach comprises a 5-step pathway. Step 1 is the screening for impairment in functions, and Step 2 is an in-depth evaluation to confirm the presence and severity of functional impairment. These initial two steps are crucial to determine the subsequent plan of care (Step 3) and follow-up (Step 4). The fifth step encompasses actions to support families and caregivers and to engage communities. This review gathers data from the literature on the prevalence of positive screenings regarding intrinsic capacity detected by the program's first-step screening tool, and on currently available results regarding the instrument's sensitivity and specificity. METHODS AND FINDINGS: Electronic searches were conducted in the PubMed, Cochrane, Embase, and SciElo databases, the medRxiv platform, and recent human aging scientific events, looking for research analyzing the ICOPE screening instrument. Studies reporting data on the prevalence of positive screenings for loss of intrinsic capacity using the proposed screening tool and/or findings on the instrument's sensitivity and specificity were included. A total of 7 publications with participants aged 50 years or more were selected. The prevalence of at least one impairment in intrinsic capacity detected by the instrument varied among the studies from 17.1 % to 94.3 %. Sensitivity ranged from 26.4 % to 100 % and specificity from 22 % to 96 %, depending on the setting and the assessed domain. CONCLUSION: Currently available data are heterogeneous, and different results were found among the studies due to diverse settings and methodologies. The evidence on the ICOPE screening tool's performance in different populations is still scarce and reinforces the need for further research worldwide.

Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated with Cognitive Impairment in Older Adults: A Cross-Sectional Study.

Background: Type 2 Deiodinase (DIO2) converts thyroxine (T4) into the active hormone triiodothyronine (T3). Thr92Ala DIO2 polymorphism has been associated with reduced conversion of T4 into T3 and central nervous system hypothyroidism. However, how Thr92Ala DIO2 polymorphism affects cognitive function is still unclear. Objective: To assess the association between Thr92Ala DIO2 polymorphism and cognitive performance in older adults. Design: Cross-sectional study. Setting: University-based tertiary hospital in Brazil. Patients: > 65-year-old with no limiting clinical disease. Interventions: All participants answered a standard questionnaire before undergoing thyroid function laboratory evaluation and genotyping of the Thr92Ala DIO2 polymorphism. Main Outcomes: Cognitive impairment measured by the Word List Memory task from the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) and the Brief Cognitive Screening Battery (BCSB). Results: A hundred individuals were included. Clinical and laboratory characteristics were similar among DIO2 genotypes (all p > 0.05). No differences were found in the Word List Memory, recall, or recognition tests of the CERAD-NB assuming a recessive model for the Ala/Ala vs. Thr/Ala-Thr/Thr genotypes. Results of Clock Drawing Test, Animal Fluency Test, Mini-Mental State Exam, and Figure Memory Test of the BCSB were similar between groups. Conclusions: These findings suggest that Thr92Ala DIO2 polymorphism is not associated with relevant cognitive impairment in older adults.

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. Three more were identified through manual search, being 301 studies revised for inclusion. 278 were excluded during title/abstract review. After further evaluation of 23 full-texts, 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 meta-analysis 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 meta-analysis. 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.

Sleep duration and mortality in the elderly: a systematic review with meta-analysis.

OBJECTIVE: The purpose of our study was to evaluate the association between short and long sleep duration and all-cause and cardiovascular mortality among elderly individuals. DESIGN: Systematic review and meta-analysis of population-based cohort studies. SETTING: Articles were retrieved from international and national electronic databases. STUDY SELECTION: Studies were identified in PubMed, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographic Index on Health Sciences from Spain) and CAPES (PhD thesis repository) between 1980 and 2015. Studies which met all criteria were eligible: participants aged 60 years or over, assessment of sleep duration as 24 h, nighttime or daytime sleep, evaluation of all-cause or cause-specific mortality, population-based cohort studies conducted on representative samples. There was no language restriction and studies published as abstracts were excluded. DATA EXTRACTION: Data were analysed using the Comprehensive Meta-Analysis software (V.3.3.070), and summary estimates (relative risk (RR), 95% CI) were calculated using a random effects model. Heterogeneity and consistency were evaluated through Cochran's Q and the I(2) statistics, respectively, and sensitivity analyses were conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and cardiovascular mortality. RESULTS: Overall, 27 cohort studies were selected, comprising >70,000 elderly individuals, and followed up from 3.4 to 35 years. In the pooled analysis, long and short sleep duration were associated with increased all-cause mortality (RR 1.33; 95% CI 1.24 to 1.43 and RR 1.07; 95% CI 1.03 to 1.11, respectively), compared with the reference category. For cardiovascular mortality, the pooled relative risks were 1.43 (95% CI 1.15 to 1.78) for long sleep, and 1.18 (95% CI 0.76 to 1.84) for short sleep. Daytime napping ≥ 30 min was associated with risk of all-cause mortality (RR 1.27; 95% CI 1.08 to 1.49), compared with no daytime sleep, but longer sleep duration (≥ 2.0 h) was not (RR 1.34; 95% CI 1.95 to 1.90). CONCLUSIONS: Among elderly individuals, long and short sleep duration are associated with increased risk for all-cause mortality. Long sleep duration is associated with cardiovascular mortality.