A systematic review and meta-analysis investigating the relationship between metabolic syndrome and the incidence of thyroid diseases.

PURPOSE To assess the prospective association between metabolic syndrome (MetS), its components, and incidence of thyroid disorders by conducting a systematic review and meta-analysis. METHODS A systematic search was performed in Ovid Medline, Embase.com, and Cochrane CENTRAL from inception to February 22, 2023. Publications from prospective studies were included if they provided data on baseline MetS status or one of its components and assessed the incidence of thyroid disorders over time. A random effects meta-analysis was conducted to calculate the odds ratio (OR) for developing thyroid disorders. RESULTS After full-text screening of 2927 articles, seven studies met our inclusion criteria. Two of these studies assessed MetS as an exposure (N = 71,727) and were included in our meta-analysis. The association between MetS at baseline and incidence of overt hypothyroidism at follow-up yielded an OR of 0.78 (95% confidence interval [CI]: 0.52-1.16 for two studies, I2 = 0%). Pooled analysis was not possible for subclinical hypothyroidism, due to large heterogeneity (I2 = 92.3%), nor for hyperthyroidism, as only one study assessed this association. We found evidence of an increased risk of overt (RR: 3.10 (1.56-4.64, I2 = 0%) and subclinical hypothyroidism (RR 1.50 (1.05-1.94), I2 = 0%) in individuals with obesity at baseline. There was a lower odds of developing overt hyperthyroidism in individuals with prediabetes at baseline (OR: 0.68 (0.47-0.98), I2 = 0%). CONCLUSIONS We were unable to draw firm conclusions regarding the association between MetS and the incidence of thyroid disorders due to the limited number of available studies and the presence of important heterogeneity in reporting results. However, we did find an association between obesity at baseline and incidence of overt and subclinical hypothyroidism

Systematic Literature Review of the Natural History of Spinal Muscular Atrophy: Motor Function, Scoliosis, and Contractures.

BACKGROUND AND OBJECTIVES Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA. METHODS Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with Types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Datasets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves. RESULTS Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (three on the probability of sitting in patients with Types 2 and 3 SMA, and eight on the probability of walking/ambulation in patients with Type 3 SMA). The median time to loss of sitting (95% confidence interval [CI]) was 14.5 years (14.1-31.5) for the Type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for Type 3a SMA (disease onset at age <3 years) and 44.2 years (43.0-49.4) for Type 3b SMA (disease onset at age ≥3 years). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data. DISCUSSION Results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. Additionally, data suggest that untreated patients with Types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with Types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes

How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison

Aim: To conduct indirect treatment comparisons between risdiplam and other approved treatments for spinal muscular atrophy (SMA). Patients &amp; methods: Individual patient data from risdiplam trials were compared with aggregated data from published studies of nusinersen and onasemnogene abeparvovec, accounting for heterogeneity across studies. Results: In Type 1 SMA, studies of risdiplam and nusinersen included similar populations. Indirect comparison results found improved survival and motor function with risdiplam versus nusinersen. Comparison with onasemnogene abeparvovec in Type 1 SMA and with nusinersen in Types 2/3 SMA was challenging due to substantial differences in study populations; no concrete conclusions could be drawn from the indirect comparison analyses. Conclusion: Indirect comparisons support risdiplam as a superior alternative to nusinersen in Type 1 SMA.</p