A meta-analysis of the prevalence of neuropsychiatric disorders and their association with disease onset in myotonic dystrophy.

There is a high prevalence of neuropsychiatric disorders in myotonic dystrophy types 1 and 2 (DM1 and DM2), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in DM1, and depression and anxiety in both DMs. The aim of this systematic review and meta-analysis was to estimate the prevalence of ASD, ADHD, depression and anxiety in the population with DM, and their association with disease onset. A systematic search of Medline, Scopus, Web of Science, and the Cochrane Library was conducted from inception to November 2023. Observational studies estimating the prevalence of these disorders in DM1 or DM2 were included. A meta-analysis of the prevalence of these disorders and an association study with disease onset by prevalence ratio meta-analysis were performed. Thirty-eight studies were included. In DM1, the prevalence of ASD was 14%, with congenital onset being 79% more common than juvenile onset, while the prevalence of ADHD was 21%, with no difference between congenital and juvenile onset, and the prevalence of depression and anxiety were 14% and 16%. Depression was more common in the adult onset. Finally, the prevalence of depression in DM2 was 16%. A higher prevalence of neuropsychiatric disorders is observed in individuals with DM1 and DM2 than in the general population. Therefore, actively screening for congenital and juvenile neurodevelopmental disorders in DM1 and emotional disorders in DM1 and DM2 may improve the quality of life of those affected.

Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review.

BACKGROUND: Vamorolone has recently been approved for the management of Duchenne muscular dystrophy to replace glucocorticosteroids, which theoretically have more side effects. However, its efficacy and safety profile is unclear. OBJECTIVE: We aimed to assess the efficacy of vamorolone in Duchenne muscular dystrophy through the 6-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA), time to stand velocity (TTSTAND), time to run 10 m (TTRW), time to climb four stairs (TTCLIMB) and a safety profile. METHODS: A systematic search was conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to June 2024 (PROSPERO: CRD42024558413) for studies evaluating the effect or safety profile of vamorolone in a population with Duchenne muscular dystrophy on 6MWT, NSAA and TTSTAND. TTRW, TTCLIMB and a safety profile were included. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool (RoB2) and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute, depending on the type of design. Results were expressed as mean differences or proportions with 95% confidence intervals (CIs), depending on the outcome. RESULTS: Six studies with a total of 145 individuals with Duchenne muscular dystrophy and a baseline age between 4.7 and 5.5 years were included in the systematic review. Overall, the most effective dose was 6 mg/kg/day. At 24 weeks, this dose showed a statistically significant effect compared with the untreated cohorts of 41.60 m (95% CI 14.30, 68.90) on the 6MWT, 3.57 points (95% CI 1.89, 5.25) on the NSAA, 0.06 events/s (95% CI 0.02, 0.10) on the TTSTAND, approximately 0.25 m/s on the TTRW and 0.04 (95% CI -0.00, 0.08) to 0.07 events/s (95% CI 0.03, 0.11) on the TTCLIMB. There was some discrepancy in the statistical significance of some studies, although the direction of the effect was usually similar. In general, the effect was maintained in the extension studies. Adverse events were less frequent than in historical cohorts treated with glucocorticoids. Finally, the risk of bias in the included studies was low. CONCLUSIONS: According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis.

Association between pulse wave velocity and white matter hyperintensities among older adults: A meta-analysis of cross-sectional and longitudinal studies.

BACKGROUND: Higher levels of pulse wave velocity (PWV) have been related with the presence of small vessel disease that could damage the brain, in which white matter hyperintensities (WMH) could be presented as consequence. This meta-analysis aims to examine the cross-sectional and longitudinal associations between PWV and the presence of WMH among older adults. METHODS: We searched PubMed, Scopus, and WOS until June 2024. Pooled Odds Ratio (p-OR) were estimated for the cross-sectional and longitudinal associations between PWV and WMH. In addition, we explored whether this associations could be modified by type of PWV measurement and study and sample characteristics. RESULTS: The p-OR between PWV and WMH was 1.16 (95 % CI, 1.10-1.22) for the cross-sectional and 1.07 (95 %, 1.00-1.15) for the longitudinal association. Similar figures were found by type of PWV measurement and no one of the explored characteristics modified this associations. CONCLUSIONS: This meta-analysis revealed that the presence in and the long-term development of WMHs among older adults are more likely among those with elevated PWV.

Comparative effect of different types of physical exercise and intensity levels on low birth weight: A systematic review and network meta-analysis.

BACKGROUND: Low birth weight (LBW) has been established as a major determinant of neonatal mortality and morbidity. However, there is no evidence of the effectiveness of different types of physical exercise (PE) at different intensities during pregnancy to prevent LBW. OBJECTIVES: To compare the effectiveness of different types of PE at different levels of intensity in pregnant women to prevent LBW. DESIGN: A systematic review and network meta-analysis was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols for Network Meta-Analysis extension statement. DATA SOURCES AND METHODS: We searched the PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases from inception to November 2023. We included randomized controlled trials (RCTs). A random effects method was used to calculate the pooled mean difference (MD). The effect of each intervention was calculated using a network meta-analysis with a frequentist perspective. RESULTS: Forty-three RCTs were included in the systematic review, and 38 RCTs were included in the network meta-analysis. In the general population, although no significant results, the MDs for light-moderate strength, moderate-vigorous strength, and moderate-vigorous Pilates exercises were favorable for preventing LBW. Furthermore, moderate-vigorous strength exercise was effective to prevent LBW, reporting significant MD compared to control groups in the healthy population (310.00, 95% confidence interval: 78.40, 541.60; I2 = 81.3%). CONCLUSION: Strength exercises at a moderate-vigorous intensity could be a potential strategy for the prevention of LBW in the healthy population. However, our findings should be interpreted with caution because the overall risk of bias was between "some concerns" and "high," and the overall certainty of the evidence was low. REGISTRATION: PROSPERO CRD42023401770.

Real-world effectiveness and safety of erenumab for the treatment of migraine: A systematic review and meta-analysis.

BACKGROUND: Migraine is a common and disabling primary headache disorder. Several drugs targeting calcitonin gene-related peptide (CGRP), such as erenumab (an anti-CGRP receptor mAb), have been developed recently. However, the real-world effects of erenumab are not well understood. OBJECTIVE: To assess the clinical effectiveness and safety of erenumab for reducing migraine intensity and frequency in the real world. METHODS: A systematic search of PubMed, Scopus, Web of Science and the Cochrane Library was conducted from inception to December 2023. Studies estimating the real-world effect of erenumab on monthly migraine days (MMD), monthly headache days (MHD), headache impact test (HIT-6), number of days in medication (NDM), acute monthly intake (AMI), pain intensity (PI) and safety outcomes were included. Meta-analyses of proportions or mean differences were performed. RESULTS: Fifty-three studies were included. At 3-months, the effect was -7.18 days for MMD, -6.89 days for MHD, -6.97 for HIT-6, -6.22 days for NDM, -15.75 for AMI, and -1.71 for PI. Generally, the effect at 6- and 12-months increased slightly and gradually. The MMD/MHD response rates revealed that approximately one-third of patients exhibited a response greater than 30%, while one-sixth demonstrated a response exceeding 50%. Additionally, 3-4% of patients achieved a response rate of 100%. Adverse event rates were 0.34 and 0.43 at 6- and 12-months, respectively. CONCLUSION: This study provides strong evidence of the effectiveness and safety of erenumab in the real world; to our knowledge, this is the first real-world meta-analysis specific to erenumab. Erenumab represents a solid therapeutic option for physicians.

Measles Outbreak Associated with a Migrant Shelter - Chicago, Illinois, February-May 2024.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.

Exploring the Influence of Insulin Resistance on Arterial Stiffness in Healthy Adults: From the Metabolic and Cardiovascular Health Insights of the EVasCu Study.

Previous evidence associates insulin resistance with arterial stiffness in various pathologies, yet limited reports exist in healthy adults. Therefore, this study aims to estimate the association between insulin resistance and arterial stiffness in healthy adults. The cross-sectional EVasCu study enrolled 390 participants (42.05 ± 13.15 years). ANCOVAs, unadjusted (model 1) and adjusted (model 2), explored the association between arterial stiffness markers (aortic Pulse Wave Velocity [aPWV], Augmentation Index [AIx@75] and Cardio-Ankle Vascular Index [CAVI]), and insulin resistance markers (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], Quantitative Insulin Sensitivity Check Index [QUICKI] and Triglycerides-Glucose [TyG]). In model 1, all insulin resistance markers were associated with aPWV, HOMA-IR and QUICKI were associated with AIx@75, and the TyG index was associated with CAVI. In model 2, HOMA-IR and QUICKI increased aPWV by 0.179 and 0.156 m/s (p = 0.001 and p = 0.011), and AIx@75 by 4.17 and 5.39% (p = 0.009 and p = 0.003). The EVasCu study offers valuable insights into the relationship between insulin resistance and arterial stiffness in healthy adults, providing a deeper understanding of metabolic and cardiovascular health. By examining this influence, we embark on an intriguing exploration of how these factors interplay in the human body.

Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Correction: Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Correction for 'Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis' by Alicia Saz-Lara et al., Food Funct., 2024, https://doi.org/10.1039/D3FO05061K.

Differences in quality of life and fitness level among men and women in the adulthood: a cross-sectional analysis.

BACKGROUND: This study aimed to examine the associations between physical fitness components and health-related quality of life (HRQoL) among adults stratified by sex and age. In addition, we aimed to examine whether these associations change based on socioeconomic, clinical, and biochemical characteristics. METHODS: A total of 297 participants aged 47.41 (standard deviation: 9.08) years from the "Validity of a Model of Accelerated Vascular Aging as a Cardiovascular Risk Index in Healthy Adults: the EVasCu cross-sectional study" were included in this analysis. HRQoL, physical fitness, socioeconomic status (SES), waist circumference, and blood pressure were measured. Additionally, blood samples were extracted to determine cholesterol, triglyceride, and glycated hemoglobin A1c (HbA1c) levels. Analyses of covariance (ANCOVAs) were estimated to test mean differences in physical and mental health-related health measures (HRQoL) between fitness categories (fixed factors) by sex and age categories. RESULTS: The physical HRQoL was related to the levels of fitness parameters among women, independent of age, while for men, it was related to better levels of general fitness and cardiorespiratory fitness among men aged < 50 and men aged ≥ 50, respectively. In contrast, mental HRQoL was related to cardiorespiratory fitness only among women aged < 50 years; speed/agility and flexibility among men aged < 50 years; and general fitness, strength, and flexibility among men aged ≥ 50 years. These data did not change when SES, clinical variables, or biochemical determinations were included in the analyses, neither for the physical nor for the mental HRQoL. CONCLUSION: Gender and age are important factors to be considered when analysing health indicators and influences in the population. In addition, SES, clinical characteristics, and biochemical parameters do not seem to influence the relationship between HRQoL and fitness.

Steps per day and health-related quality of life in schoolchildren: the mediator role of cardiorespiratory fitness.

To analyse the relationship between steps per day and health-related quality of life (HRQoL) and cardiorespiratory fitness (CRF) and to examine whether the relationship between steps per day and HRQoL is mediated by CRF in schoolchildren. This was a cross-sectional study including 501 schoolchildren (aged 9-12 years, 47% girls), from Cuenca, Spain. Steps per day were measured using the Xiaomi Mi Band 3 Smart Bracelet, HRQoL was estimated by the KIDSCREEN-27 questionnaire, and CRF was assessed using the 20-m shuttle run test. Analysis of covariance and multivariate analysis of covariance models showed that children with a higher mean number of steps per day (> 9000 steps/day) had better HRQoL (global score, and physical and psychological well-being) and higher CRF levels than their peers with a lower number of steps per day (p < 0.05); however, these differences were no longer significant when controlling for sex, age, mother's education level, and CRF (p > 0.05). Linear regression models estimated that each 1000-step increment was associated with better CRF (ß = 0.350; 95% CI, 0.192 to 0.508). In addition, the relationship between steps per day and HRQoL was mediated by CRF (p < 0.05).    Conclusion: Steps per day are a good metric to estimate daily physical activity because of its positive relationship with CRF. Moreover, those children taking more than 9000 steps per day are associated with higher levels of physical and psychological well-being. Finally, a substantial part of the improvement in HRQoL achieved through the increase in physical activity (steps per day) is mediated by CRF. What is Known: • Physical activity is known to have a positive impact on health-related quality of life in children. Steps per day are commonly used as a measure of physical activity. • Cardiorespiratory fitness is a recognized indicator of overall health in youth. What is New: • Increments of steps per day were associated with better CRF, with a nonlinear association after approximately 9000 steps/day. • Schoolchildren with > 9000 steps/ day showed better HRQoL.

Association between wine consumption and cancer: a systematic review and meta-analysis.

Background: Alcohol consumption is related to the risk of developing different types of cancer. However, unlike other alcoholic beverages, moderate wine drinking has demonstrated a protective effect on the risk of developing several types of cancer. Objective: To analyze the association between wine consumption and the risk of developing cancer. Methods: We searched the MEDLINE (through PubMed), Scopus, Cochrane, and Web of Science databases to conduct this systematic review and meta-analysis. Pooled relative risks (RRs) were calculated using the DerSimonian and Laird methods. I2 was used to evaluate inconsistency, the τ2 test was used to assess heterogeneity, and The Newcastle-Ottawa Quality Assessment Scale were applied to evaluate the risk of bias. This study was previously registered in PROSPERO, with the registration number CRD42022315864. Results: Seventy-three studies were included in the systematic review, and 26 were included in the meta-analysis. The pooled RR for the effect of wine consumption on the risk of gynecological cancers was 1.03 (95% CI: 0.99, 1.08), that for colorectal cancer was 0.92 (95% CI: 0.82, 1.03), and that for renal cancer was 0.92 (95% CI: 0.81, 1.04). In general, the heterogeneity was substantial. Conclusion: The study findings reveal no association between wine consumption and the risk of developing any type of cancer. Moreover, wine drinking demonstrated a protective trend regarding the risk of developing pancreatic, skin, lung, and brain cancer as well as cancer in general. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022315864, identifier CRD42022315864 (PROSPERO).

Early vascular aging as an index of cardiovascular risk in healthy adults: confirmatory factor analysis from the EVasCu study.

BACKGROUND: The concept of early vascular aging (EVA) represents a potentially beneficial model for future research into the pathophysiological mechanisms underlying the early manifestations of cardiovascular disease. For this reason, the aims of this study were to verify by confirmatory factor analysis the concept of EVA on a single factor based on vascular, clinical and biochemical parameters in a healthy adult population and to develop a statistical model to estimate the EVA index from variables collected in a dataset to classify patients into different cardiovascular risk groups: healthy vascular aging (HVA) and EVA. METHODS: The EVasCu study, a cross-sectional study, was based on data obtained from 390 healthy adults. To examine the construct validity of a single-factor model to measure accelerated vascular aging, different models including vascular, clinical and biochemical parameters were examined. In addition, unsupervised clustering techniques (using both K-means and hierarchical methods) were used to identify groups of patients sharing similar characteristics in terms of the analysed variables to classify patients into different cardiovascular risk groups: HVA and EVA. RESULTS: Our data show that a single-factor model including pulse pressure, glycated hemoglobin A1c, pulse wave velocity and advanced glycation end products shows the best construct validity for the EVA index. The optimal value of the risk groups to separate patients is K = 2 (HVA and EVA). CONCLUSIONS: The EVA index proved to be an adequate model to classify patients into different cardiovascular risk groups, which could be valuable in guiding future preventive and therapeutic interventions.

Association between Wine Consumption with Cardiovascular Disease and Cardiovascular Mortality: A Systematic Review and Meta-Analysis.

Background: The objective of this systematic review and meta-analysis was: (i) to examine the association between wine consumption and cardiovascular mortality, cardiovascular disease (CVD), and coronary heart disease (CHD) and (ii) to analyse whether this association could be influenced by personal and study factors, including the participants' mean age, the percentage of female subjects, follow-up time and percentage of current smokers. Methods: In order to conduct this systematic review and meta-analysis, we searched several databases for longitudinal studies from their inception to March 2023. This study was previously registered with PROSPERO (CRD42021293568). Results: This systematic review included 25 studies, of which the meta-analysis included 22 studies. The pooled RR for the association of wine consumption and the risk of CHD using the DerSimonian and Laird approach was 0.76 (95% CIs: 0.69, 0.84), for the risk of CVD was 0.83 (95% CIs: 0.70, 0.98), and for the risk of cardiovascular mortality was 0.73 (95% CIs: 0.59, 0.90). Conclusions: This research revealed that wine consumption has an inverse relationship to cardiovascular mortality, CVD, and CHD. Age, the proportion of women in the samples, and follow-up time did not influence this association. Interpreting these findings with prudence was necessary because increasing wine intake might be harmful to individuals who are vulnerable to alcohol because of age, medication, or their pathologies.

Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.

BACKGROUND: Germline CDH1 pathogenic or likely pathogenic variants cause hereditary diffuse gastric cancer (HDGC). Once a genetic cause is identified, stomachs' and breasts' surveillance and/or prophylactic surgery is offered to asymptomatic CDH1 carriers, which is life-saving. Herein, we characterized an inherited mechanism responsible for extremely early-onset gastric cancer and atypical HDGC high penetrance. METHODS: Whole-exome sequencing (WES) re-analysis was performed in an unsolved HDGC family. Accessible chromatin and CDH1 promoter interactors were evaluated in normal stomach by ATAC-seq and 4C-seq, and functional analysis was performed using CRISPR-Cas9, RNA-seq and pathway analysis. RESULTS: We identified a germline heterozygous 23 Kb CDH1-TANGO6 deletion in a family with eight diffuse gastric cancers, six before age 30. Atypical HDGC high penetrance and young cancer-onset argued towards a role for the deleted region downstream of CDH1, which we proved to present accessible chromatin, and CDH1 promoter interactors in normal stomach. CRISPR-Cas9 edited cells mimicking the CDH1-TANGO6 deletion display the strongest CDH1 mRNA downregulation, more impacted adhesion-associated, type-I interferon immune-associated and oncogenic signalling pathways, compared to wild-type or CDH1-deleted cells. This finding solved an 18-year family odyssey and engaged carrier family members in a cancer prevention pathway of care. CONCLUSION: In this work, we demonstrated that regulatory elements lying down-stream of CDH1 are part of a chromatin network that control CDH1 expression and influence cell transcriptome and associated signalling pathways, likely explaining high disease penetrance and very young cancer-onset. This study highlights the importance of incorporating scientific-technological updates and clinical guidelines in routine diagnosis, given their impact in timely genetic diagnosis and disease prevention.

Association between arterial stiffness and orthostatic hypotension: A systematic review and meta-analysis.

Background: Orthostatic hypotension, defined as a decrease in blood pressure on standing, is associated with an increased risk of mortality and cardiovascular events in the general population. In addition, it has recently been suggested that arterial stiffness is independently associated with orthostatic hypotension, which may be due to a loss of the buffering effect of the ascending aorta and an early return of pressure waves. However, the specific mechanisms underlying this association remain unclear. Thus, we aimed to evaluate the association between orthostatic hypotension and arterial stiffness in the adult population. Methods: PubMed, Scopus, Web of Science, and Cochrane Library databases were searched from inception to 31 January 2022. The DerSimonian and Laird method was used to calculate pooled odds ratio (OR) estimates and their respective 95% confidence intervals (95% CI) for the association between orthostatic hypotension and arterial stiffness. Results: Overall, 11 studies were included, with a total of 10,611 subjects. Our results showed that increased arterial stiffness raises the risk of orthostatic hypotension (OR: 1.40, 95% CI: 1.28-1.54), with a stronger association at central arterial stiffness (OR: 1.50, 95% CI: 1.34-1.68) than at peripheral arterial stiffness (OR: 1.29, 95% CI: 1.17-1.43). Conclusion: Our findings showed that increased arterial stiffness raises the risk of orthostatic hypotension by 40% among the adult population. Considering that orthostatic hypotension, which is usually a consequence of antihypertensive treatment, has been widely associated with the risk of cardiovascular events, appropriate control of arterial stiffness could be a clinical strategy to prevent cardiovascular morbidity and mortality.

Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

The aim of this systematic review was to analyse whether there is an association between severe hypoglycaemia and the incidence of dementia in patients with type 2 diabetes mellitus. We systematically searched the MEDLINE, Scopus, and Cochrane databases from their inception until September 2022 for observational studies on the association between hypoglycaemia and the risk of dementia. The DerSimonian and Laird method was used to compute a pooled estimate of the risk for such association. Risk ratio (RR) and its respective 95% confidence interval (95% CI). Two analyses were performed to estimate the risk of dementia: (i) any hypoglycaemia versus no hypoglycaemia and (ii) a dose-response analysis for one, two, or more than three hypoglycemic events versus no hypoglycaemia. PROSPERO registration number CRD42020219200. Seven studies were included. The pooled RR for the association of severe hypoglycaemia and risk of dementia was 1.47 (95% CI: 1.24-1.74). When the dose-response trend was analysed, the pooled RR for the risk of dementia was increased according to the hypoglycaemia events as follows: 1.29 (95% CI: 1.15-1.44) for one hypoglycemic event; 1.68 (95% CI: 1.38-2.04) for two hypoglycemic events; and 1.99 (95% CI: 1.48-2.68) for three or more hypoglycemic events. Our study demonstrates a 54% higher risk of dementia among people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Considering our results and the prevalence of people suffering from diabetes mellitus, health education for both newly diagnosed and already diagnosed people could be a useful tool for glycaemic control, thus avoiding hypoglycaemic events.

Onasemnogene Abeparvovec in Type 1 Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis.

One of the latest approved therapies for spinal muscular atrophy (SMA) is onasemnogene abeparvovec, which transduces motor neurons with the survival of motor neuron gene. The aim of this meta-analysis was to estimate the effect of onasemnogene abeparvovec on motor function in participants with type 1 SMA. Medline, Web of Science, Scopus, and Cochrane Library were searched for studies published from inception to August 2022. Pre-post clinical trials and observational studies determining the effect of onasemnogene abeparvovec on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score or motor milestones (i.e., head control, sit unassisted, feed orally, not use permanent ventilatory support, crawl, stand alone, and walk alone) in participants with type 1 SMA were included. Continuous outcomes (i.e., CHOP-INTEND score) were expressed as pre-post mean difference and 95% confidence interval (CI), while the proportion of participants who achieved >40, >50, and >58/60 points on the CHOP-INTEND and the achievement of the motor milestones were expressed as proportions and 95% CI. A random effects meta-analysis was conducted on each outcome, and the baseline CHOP-INTEND score was considered a covariate. Eleven studies were included in the systematic review, and four were included in the meta-analyses. Onasemnogene abeparvovec improved CHOP-INTEND scores by 11.06 (9.47 to 12.65) and 14.14 (12.42 to 15.86) points at 3 and 6 months postinfusion, respectively. Moreover, 87%, 51%, and 12% achieved CHOP-INTEND scores of >40, >50, and >58/60 points, respectively. However, this proportion increased to 100% in presymptomatic participants with greater baseline CHOP-INTEND. Motor milestones were also improved, especially in presymptomatic participants. Our systematic review not only showed a marked improvement in motor function in type 1 SMA but also showed that treatment in the presymptomatic stage improves the development of these children toward an evolution close to normal for their age.

Is cardiorespiratory fitness a moderator of the relationship between sugar-sweetened beverage consumption and insulin resistance in schoolchildren?

PURPOSE: The aim of this study was to determine whether cardiorespiratory fitness (CRF) decreases the association between insulin resistance and sugar-sweetened beverage (SSB) consumption in a population-based sample of Spanish schoolchildren. METHODS: This is a cross-sectional study including 430 schoolchildren (51.4% girls), aged 8-12 years, from 10 schools in Cuenca (Spain). Blood samples were drawn to measure fasting insulin levels. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also assessed. Data on SSB consumption were gathered using the Children's Eating Habits Questionnaire, which was completed by parents. The CRF level was determined by the 20 m Shuttle Run test and a curvilinear allometric model. RESULTS: Our conditional regression estimates showed that CRF moderated the association of SSB consumption on insulin levels or HOMA-IR. In children who had levels of CRF < 34.4 ml/kg/min ml/kg/min (for insulin levels) or < 33.6 ml/kg/min (for HOMA-IR), the association between SSB consumption and fasting insulin levels or HOMA-IR raised. Among children with CRF levels between 34.4 and 52.1 ml/kg/min (for insulin levels) or 33.6-55.4 ml/kg/min (for HOMA-IR), the association of SSB consumption on insulin level or HOMA-IR neither increased nor decreased. Among children with CRF levels > 52.1 ml/kg/min (for insulin levels) or > 55.4 ml/kg/min (for HOMA-IR), the association of SSB consumption on fasting insulin levels or HOMA-IR decreased. CONCLUSIONS: Our results showed that certain levels of CRF moderate the association between SSB consumption and insulin resistance in a population-based sample of Spanish schoolchildren.