Validation of an early vascular aging construct model for comprehensive cardiovascular risk assessment using external risk indicators for improved clinical utility: data from the EVasCu study.

BACKGROUND: Cardiovascular diseases (CVDs) remain a major global health concern, necessitating advanced risk assessment beyond traditional factors. Early vascular aging (EVA), characterized by accelerated vascular changes, has gained importance in cardiovascular risk assessment. METHODS: The EVasCu study in Spain examined 390 healthy participants using noninvasive measurements. A construct of four variables (Pulse Pressure, Pulse Wave Velocity, Glycated Hemoglobin, Advanced Glycation End Products) was used for clustering. K-means clustering with principal component analysis revealed two clusters, healthy vascular aging (HVA) and early vascular aging (EVA). External validation variables included sociodemographic, adiposity, glycemic, inflammatory, lipid profile, vascular, and blood pressure factors. RESULTS: EVA cluster participants were older and exhibited higher adiposity, poorer glycemic control, dyslipidemia, altered vascular properties, and higher blood pressure. Significant differences were observed for age, smoking status, body mass index, waist circumference, fat percentage, glucose, insulin, C-reactive protein, diabetes prevalence, lipid profiles, arterial stiffness, and blood pressure levels. These findings demonstrate the association between traditional cardiovascular risk factors and EVA. CONCLUSIONS: This study validates a clustering model for EVA and highlights its association with established risk factors. EVA assessment can be integrated into clinical practice, allowing early intervention and personalized cardiovascular risk management.

Non-invasive skin autofluorescence as a screening method for diabetic retinopathy.

Diabetic retinopathy (DR) is a public health problem and a common cause of blindness. It is diagnosed by fundus examination; however, this is a costly and time-consuming method. Non-invasive skin autofluorescence (SAF) may be an accessible, fast and simple alternative for screening and early diagnosis of DR. The aim of this study was to evaluate the accuracy of SAF as a screening method for DR. A systematic search of MEDLINE, Scopus, and Web of Science databases was performed. Random effects models for sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (dOR) value and 95% CIs were used to calculate test accuracy. In addition, hierarchical summary receiver operating characteristic curves (HSROC) were used to summarise the overall test performance. Four studies were included in the meta-analysis. Pooled sensitivity and specificity were 0.79 (95% CI 0.72-0.88; I2  = 0.0%) and 0.54 (95% CI 0.32-0.92; I2  = 97.0%), respectively. The dOR value for the diagnosis of DR using SAF was 5.11 (95% CI 1.81-14.48: I2  = 85.9%). The PRL was 2.17 (95% CI 0.62-7.64) and the NRL was 0.27 (95% CI 0.07-1.03). Heterogeneity was not relevant in sensitivity and considerable in specificity. The 95% confidence region of the HSROC included all studies. SAF as a screening test for DR shows sufficient accuracy for its use in clinical settings. SAF may be an appropriate method for DR screening, and further research is needed to recommend it as a diagnostic method.

Prevalence and genotypic associations of epilepsy in Prader-Willi Syndrome: A systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS). METHODS: A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed. RESULTS: Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures. CONCLUSIONS: The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed.

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 of daily steps on lipid and glycaemic profiles in children: The mediator role of cardiorespiratory fitness.

AIM: To analyse, in schoolchildren, the relationship between daily steps with metabolic parameters; and to examine whether this association is mediated by cardiorespiratory-fitness (CRF). METHODS: A cross-sectional analysis of baseline data from a feasibility trial was performed in children from two primary schools in Cuenca, Spain. Daily steps were measured using the Xiaomi MI Band 3. Lipid and glycaemic profiles were analysed from blood samples. CRF was assessed using the 20-m shuttle run test. ANCOVA models were used to test the mean differences by daily steps quartiles. Mediation analyses were conducted to examine whether CRF mediates the association between daily steps and lipid and glycaemic parameters. RESULTS: A total of 159 schoolchildren (aged 9-12 years, 53% female) were included in the analysis. Schoolchildren in the highest daily steps quartiles (>10 000 steps) showed significantly lower triglycerides and insulin levels (p = 0.004 and 0.002, respectively). This association did not remain after controlling for CRF. In mediation analyses, a significant indirect effect was observed through CRF in the relationship between daily steps with triglycerides and insulin. CONCLUSION: Children who daily accumulate more than 10 000 steps have better lipid and metabolic profile, and CRF mediated their relationship in schoolchildren.

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.

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.

Global prevalence of intellectual developmental disorder in dystrophinopathies: A systematic review and meta-analysis.

AIM: To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD) according to the affected isoforms of the DMD gene: Dp427, Dp140, Dp71. METHOD: Systematic searches in MEDLINE, Scopus, Web of Science, and the Cochrane Library were conducted from inception of each database to March 2022. Observational studies that determined the prevalence of IDD in the population with BMD or DMD were included. Meta-analyses of IDD prevalence and prevalence ratios of the IDD-genotype association were conducted. RESULTS: Forty-nine studies were included. The prevalence of IDD in BMD was 8.0% (95% confidence interval 5.0-11.0), and in DMD it was 22.0% (18.0-27.0). Meta-analyses of IDD-genotype association showed a deleterious association between IDD and the number of isoforms affected in DMD, with a prevalence ratio = 0.43 (0.28-0.64) and 0.17 (0.09-0.34) for Dp140+ /Dp71+ versus Dp140- /Dp71+ and Dp140+ /Dp71+ versus Dp140- /Dp71- comparisons respectively. However, in BMD, there was no association for Dp140+ /Dp71+ versus Dp140- /Dp71+ . INTERPRETATION: There is a high prevalence of IDD in BMD and DMD. Moreover, the number of isoforms affected is strongly and negatively associated with the prevalence of IDD in DMD. WHAT THIS PAPER ADDS: The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy and 22% in Duchenne muscular dystrophy (DMD). The global prevalence of IDD in DMD was 12%, 29%, and 84% in participants with Dp427- /Dp140+ /Dp71+ , Dp427- /Dp140- /Dp71+ , and Dp427- /Dp140- /Dp71- genotypes respectively. In DMD, 12% and 22% of participants had abnormal performance IQ and verbal IQ values respectively.

Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess the efficacy and safety of risdiplam on motor and respiratory function in spinal muscular atrophy (SMA). We systematically searched Medline, Scopus, Web of Science, and the Cochrane Library from inception to March 2023. We included pre-post studies that determined the effect of risdiplam on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the 32-item Motor Function Measure (MFM32), the Revised Upper Limb Module (RULM), the Hammersmith Functional Motor Scale - Expanded (HFMSE), respiratory function, and the proportion of risdiplam-related adverse events in a population with SMA (phenotypes 1 and 2/3). Meta-analyses were also performed where possible. Eleven studies were included. After 12 months of treatment, 57% of participants with SMA1 achieved a CHOP-INTEND score ≥ 40 points, and more than half were able to feed orally and had head control. In SMA2/3, MFM32, RULM, and HFMSE increased by 2.09 (1.17, 3.01), 1.73 (1.25, 2.20), and 1.00 (0.40, 1.59) points, respectively. Efficacy on respiratory function in SMA2/3 was inconsistent. Finally, 16% of participants experienced adverse events, but serious adverse events could not be quantified due to a lack of cases. The limited available evidence suggests that risdiplam is an effective and safe drug for the treatment of SMA. In addition, long-term clinical benefit may be partly determined by the stage of disease at which treatment is initiated.

Intellectual Profile in Myotonic Dystrophy Type 1 and Its Association With Its Onset: A Systematic Review and Meta-Analysis.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is caused by mutations in the DMPK gene, and it is associated with cognitive deficits and intelligence below normative values. The objective of this systematic review and meta-analysis was to estimate the overall intelligence and proportion of intellectual development disorder (IDD) in the population with DM1 and its association with its onset. METHODS: Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to January 2023. Studies that determined the full intelligence quotient (FIQ) or the IDD proportion in populations with DM1 were included. Meta-analyses of the FIQ and IDD and the FIQ mean difference and IDD prevalence ratios (PRs) by disease onset, inheritance, and genotype were conducted. RESULTS: Forty-five studies were included in the meta-analyses, and all were performed in the DM1 population. The FIQ and IDD in DM1 were 77.90 (71.98, 83.81) and 0.44 (0.27, 0.60), respectively. Furthermore, DM1 onset was negatively associated with intelligence. Thus, the comparison "Congenital versus Adult" onsets resulted in an intelligence quotient of -41.61 (-47.81, -35.40) points and a PR of IDD of 9.49 (3.23, 27.89). Finally, maternal inheritance was also negatively associated, but the genotype did not have a statistically significant association. CONCLUSIONS: The alterations in intelligence in DM1 are highly associated with the onset of the disease. However, the genotype did not explain these alterations well and there may be other genetic or epigenetic factors that should be considered.

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 sleep duration and cardiovascular risk: the EVasCu cross-sectional study.

Introduction: Some cardiovascular risk markers have been associated with alterations in sleep duration in different populations; however, there is little evidence in a healthy population. Aim: The aim of the present study was to analyze the associations between sleep duration and cardiovascular risk biomarkers, including advanced glycation end-products (AGEs) measured by skin autofluorescence (SAF), maximum carotid intima-media thickness (IMTMax), aortic pulse wave velocity (a-PWV), pulse pressure (PP), and low-density lipoprotein cholesterol (LDL-C), in healthy adults (EVasCu study). Methodology: The EVasCu study included 390 participants. Simple and multiple linear regressions were performed between sleep duration and cardiovascular risk markers. ANOVA analysis and ANCOVA analysis adjusted for various covariates were then performed after categorizing sleep into 6 h, 6-8 h, and >8 h. Results: 296 participants were included in the analyses (43.97 ± 12.60 years, 63.9% female). Simple linear regressions showed an inverse association between sleep duration and SAF, IMTMax, aPWV and PP. However, in the multiple linear regression with all the covariates, the statistical significance was lost. For its part, in the ANOVA analyses, sleep duration was also associated with the same parameters, but when performing the fully adjusted ANCOVA analyses, the statistical significance for SAF was maintained (p = 0.015), obtaining a difference of 0.223 arbitrary units (p = 0.017) when comparing the group <6 h vs. > 8 h. Finally, there was no association for LDL-C. Conclusion: An inverse association was found between sleep duration and APS, which is considered a marker of cardiovascular risk. Although prospective studies are needed, it is suggested that insufficient sleep may increase cardiovascular risk, which could be a key factor in future public health policies to promote health and prevent CVD.

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.

Effect of different exercise programs on lung function in people with chronic obstructive pulmonary disease: A network meta-analysis of RCTs.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has systemic consequences and causes structural abnormalities throughout the respiratory system. It is associated with a high clinical burden worldwide. AIM: A network meta-analysis was performed to determine the effects of exercise programs on lung function measured by forced expiratory volume in the first second (FEV1), FEV1 as a percentage of the predicted value (FEV1%) and forced vital capacity in people with COPD. METHODS: A literature search was performed to March 2023. Randomized controlled trials on the effectiveness of exercise programs on lung function in people with COPD were included. A standard pairwise meta-analysis and a network meta-analysis for direct and indirect comparisons between intervention and control/nonintervention groups were carried out to calculate the standardized mean difference and 95 % CI. The risk of bias was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation tool was used to assess the quality of the evidence. RESULTS: 35 studies with a total sample of 2909 participants were included in this network meta-analysis. The highest standardized mean difference was for active mind body movement therapy programs versus control for FEV1 and FEV1% (0.71; 95 % CI 0.32 to1.09; and 0.36; 95 % CI 0.15 to 0.58, respectively), and pulmonary rehabilitation+active mind body movements therapies versus control for forced vital capacity (0.45; 95 % CI 0.07 to 0.84). CONCLUSIONS: active mind body movement therapy programs were the most effective type of exercise program to improve lung function measured by FEV1 and FEV1%; pulmonary rehabilitation+active mind body movements therapies had the greatest effects on FVC in people with COPD. Exercise programs in which the abdominal muscles are strengthened could improve lung emptying, helping to overcome airway resistance in people with COPD.

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.

Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review.

BACKGROUND: Spasticity is a very common neurological sequelae that significantly impacts the quality of life of patients, affecting more than 12 million people worldwide. Botulinum toxin is considered a reversible treatment for spasticity, but due to the large amount of available evidence, synthesis seems necessary. Therefore, we conducted an overview of existing systematic reviews and meta-analyses to evaluate the effect of botulinum toxin injections in the treatment of spasticity of different etiologies. METHODS: A systematic search of different databases, including Pubmed, Scopus, the Cochrane Library, and Web of Science, was performed from inception to February 2024. Standardized mean differences (SMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the effect of botulinum toxin compared to that of the control treatment using the Modified Ashworth Scale (MAS). All the statistical analyses were performed using STATA 15 software. RESULTS: 28 studies were included in the umbrella review. The effect of botulinum toxin injections on spasticity, as measured by the MAS, was significantly lower in all but three studies, although these studies also supported the intervention. The SMDs reported by the meta-analyses ranged from -0.98 to -0.01. CONCLUSION: Botulinum toxin injections were effective at treating spasticity of different etiologies, as indicated by the measurements on the MAS. This implies an improvement in muscle tone and, consequently, in the patient's mobility and quality of life.

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.

Comparative effect of different physical exercise training on exercise capacity and cardiac function in heart failure with preserved ejection fraction: a network meta-analysis-ExIC-FEp Study.

AIMS: This network meta-analysis aimed to compare the effect of different types of physical exercise [endurance training, endurance/resistance training, and high-intensity interval training (HIIT)] on exercise capacity and cardiac function parameters in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: A systematic search of the MEDLINE (via PubMed), Scopus, and Web of Science databases was conducted to identify experimental studies addressing the effect of different physical exercise training programmes on exercise capacity and cardiac function in heart failure with preserved ejection fraction. Comparative evaluation of the effect of exercise training type was performed by conducting a standard pairwise meta-analysis and a network meta-analysis for direct and indirect comparisons between exercise training types and controls/non-interventions. Eleven studies were included in the analysis showing that endurance training improves the main exercise capacity parameters (VO2peak, workload, exercise time, peak heart rate, VO2, and 6 min walk distance). Additionally, endurance/resistance training showed a significant effect on VO2peak, workload, early mitral annulus velocity, and early mitral/mitral annulus velocity ratio. Finally, HIIT showed a significant effect on VO2peak, VO2, and the early mitral/mitral annulus velocity ratio. CONCLUSION: Our findings support the effect of three different types of physical exercise on exercise capacity, mainly VO2peak. Additionally, endurance/resistance training and HIIT could reverse left ventricular remodelling in patients with heart failure with preserved ejection fraction. REGISTRATION: PROSPERO: CRD42021276111.

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.

Comparative Effect of Two Types of Physical Exercise for the Improvement of Exercise Capacity, Diastolic Function, Endothelial Function and Arterial Stiffness in Participants with Heart Failure with Preserved Ejection Fraction (ExIC-FEp Study): Protocol for a Randomized Controlled Trial.

(1) Background: Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for approximately 50% of all patients with HF. In the absence of pharmacological treatments that have been successful in reducing mortality or morbidity in this pathology, physical exercise is recognized as an important adjunct in the treatment of HF. Therefore, the objective of this study is to compare the efficacy of combined training and high intensity interval training (HIIT) on exercise capacity, diastolic function, endothelial function, and arterial stiffness in participants with HFpEF. (2) Methods: The ExIC-FEp study will be a single-blind, 3-arm, randomized clinical trial (RCT) conducted at the Health and Social Research Center of the University of Castilla-La Mancha. Participants with HFpEF will be randomly assigned (1:1:1) to the combined exercise, HIIT or control group to evaluate the efficacy of physical exercise programs on exercise capacity, diastolic function, endothelial function, and arterial stiffness. All participants will be examined at baseline, at three months and at six months. (3) Results: The findings of this study will be published in a peer-reviewed journal. (4) Conclusions: This RCT will represent a significant advance in the available scientific evidence on the efficacy of physical exercise in the treatment of HFpEF.