The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states. GBD 2021 analysed trends in mortality, morbidity, and disability for 371 diseases and injuries and 88 risk factors in the USA between 1990 and 2021. We used several metrics to report sources of health and health loss related to specific diseases, injuries, and risk factors. GBD 2021 methods accounted for differences in data sources and biases. The analysis of levels and trends for causes and risk factors within the same computational framework enabled comparisons across states, years, age groups, and sex. GBD 2021 estimated years lived with disability (YLDs) and disability-adjusted life-years (DALYs; the sum of years of life lost to premature mortality and YLDs) for 371 diseases and injuries, years of life lost (YLLs) and mortality for 288 causes of death, and life expectancy and healthy life expectancy (HALE). We provided estimates for 88 risk factors in relation to 155 health outcomes for 631 risk-outcome pairs and produced risk-specific estimates of summary exposure value, relative health risk, population attributable fraction, and risk-attributable burden measured in DALYs and deaths. Estimates were produced by sex (male and female), age (25 age groups from birth to ≥95 years), and year (annually between 1990 and 2021). 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws (ie, 500 random samples from the estimate's distribution). Uncertainty was propagated at each step of the estimation process. We found disparities in health outcomes and risk factors across US states. Our analysis of GBD 2021 highlighted the relative decline in life expectancy and HALE compared with other countries, as well as the impact of COVID-19 during the first 2 years of the pandemic. We found a decline in the USA's ranking of life expectancy from 1990 to 2021: in 1990, the USA ranked 35th of 204 countries and territories for males and 19th for females, but dropped to 46th for males and 47th for females in 2021. When comparing life expectancy in the best-performing and worst-performing US states against all 203 other countries and territories (excluding the USA as a whole), Hawaii (the best-ranked state in 1990 and 2021) dropped from sixth-highest life expectancy in the world for males and fourth for females in 1990 to 28th for males and 22nd for females in 2021. The worst-ranked state in 2021 ranked 107th for males (Mississippi) and 99th for females (West Virginia). 14 US states lost life expectancy over the study period, with West Virginia experiencing the greatest loss (2·7 years between 1990 and 2021). HALE ranking declines were even greater; in 1990, the USA was ranked 42nd for males and 32nd for females but dropped to 69th for males and 76th for females in 2021. When comparing HALE in the best-performing and worst-performing US states against all 203 other countries and territories, Hawaii ranked 14th highest HALE for males and fifth for females in 1990, dropping to 39th for males and 34th for females in 2021. In 2021, West Virginia-the lowest-ranked state that year-ranked 141st for males and 137th for females. Nationally, age-standardised mortality rates declined between 1990 and 2021 for many leading causes of death, most notably for ischaemic heart disease (56·1% [95% UI 55·1-57·2] decline), lung cancer (41·9% [39·7-44·6]), and breast cancer (40·9% [38·7-43·7]). Over the same period, age-standardised mortality rates increased for other causes, particularly drug use disorders (878·0% [770·1-1015·5]), chronic kidney disease (158·3% [149·6-167·9]), and falls (89·7% [79·8-95·8]). We found substantial variation in mortality rates between states, with Hawaii having the lowest age-standardised mortality rate (433·2 per 100 000 [380·6-493·4]) in 2021 and Mississippi having the highest (867·5 per 100 000 [772·6-975·7]). Hawaii had the lowest age-standardised mortality rates throughout the study period, whereas Washington, DC, experienced the most improvement (a 40·7% decline [33·2-47·3]). Only six countries had age-standardised rates of YLDs higher than the USA in 2021: Afghanistan, Lesotho, Liberia, Mozambique, South Africa, and the Central African Republic, largely because the impact of musculoskeletal disorders, mental disorders, and substance use disorders on age-standardised disability rates in the USA is so large. At the state level, eight US states had higher age-standardised YLD rates than any country in the world: West Virginia, Kentucky, Oklahoma, Pennsylvania, New Mexico, Ohio, Tennessee, and Arizona. Low back pain was the leading cause of YLDs in the USA in 1990 and 2021, although the age-standardised rate declined by 7·9% (1·8-13·0) from 1990. Depressive disorders (56·0% increase [48·2-64·3]) and drug use disorders (287·6% [247·9-329·8]) were the second-leading and third-leading causes of age-standardised YLDs in 2021. For females, mental health disorders had the highest age-standardised YLD rate, with an increase of 59·8% (50·6-68·5) between 1990 and 2021. Hawaii had the lowest age-standardised rates of YLDs for all sexes combined (12 085·3 per 100 000 [9090·8-15 557·1]), whereas West Virginia had the highest (14 832·9 per 100 000 [11 226·9-18 882·5]). At the national level, the leading GBD Level 2 risk factors for death for all sexes combined in 2021 were high systolic blood pressure, high fasting plasma glucose, and...

Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999–1.045; p < 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro, by utilizing the homozygous PTEN-induced kinase 1 knockout (PINK1^−/−) mouse model of PD. PINK1^−/− mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1^−/− mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials.

Constraint-induced movement therapy (CIMT) is a neurorehabilitation technique designed to improve upper extremity motor functions after stroke. This review aimed to investigate evidence of the effect of CIMT on upper extremity in stroke patients and to identify optimal methods to apply CIMT. Four databases (MEDLINE, EMBASE, CINHAL, and PEDro) and reference lists of relevant articles and reviews were searched. Randomized clinical trials that studied the effect of CIMT on upper extremity outcomes in stroke patients compared with other rehabilitative techniques, usual care, or no intervention were included. Methodological quality was assessed using the PEDro score. The following data were extracted for each trial: patients’ characteristics, sample size, eligibility criteria, protocols of CIMT and control groups, outcome measurements, and the PEDro score. A total of 38 trials were identified according to the inclusion criteria. The trials included were heterogeneous in CIMT protocols, time since stroke, and duration and frequency of treatment. The pooled meta-analysis of 36 trials found a heterogeneous significant effect of CIMT on upper extremity. There was no significant effect of CIMT at different durations of follow-up. The majority of included articles did not fulfill powered sample size and quality criteria. The effect of CIMT changed in terms of sample size and quality features of the articles included. These meta-analysis findings indicate that evidence for the superiority of CIMT in comparison with other rehabilitative interventions is weak. Information on the optimal dose of CIMT and optimal time to start CIMT is still limited.

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of robot-assisted gait training (RAGT) on motor impairments in people with Parkinson’s disease (PD). A computer-based systematic literature search was performed in six databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of RAGT on motor impairments in people with PD were included. GRADE approach and PEDro scale were used to determine the studies’ quality of evidence. Meta-analyses were performed by calculating the weighted mean difference (WMD) at 95% confidence interval. Seven RCTs (PEDro: 5–8) met the inclusion criteria for systematic review and meta-analyses. The meta-analysis showed significant improvement on Unified Parkinson Disease Rating Scale Part III after intervention [WMD=3.292; 95% confidence interval (CI)=1.378–5.207; P=0.000], and after 1-month follow-up (WMD=5.512; 95% CI=2.396–8.629; P=0.001). Stride length (WMD=9.283; 95% CI=7.153–11.414; P=0.00) and gait speed (WMD=0.166; 95% CI=−0.090 to 0.243; P=0.000) showed significant improvements after RAGT. Balance as measured by Berg Balance Scale was improved significantly after intervention (WMD=3.87; 95% CI=0.374–6.735; P=0.029) and at 1-month follow-up (WMD=3.87; 95% CI=1.324–6.413; P=0.002). The pooled analysis did not detect any significant changes regarding stride time, cadence and functional balance scales. GRADE level of evidence ranged between high and low. The RAGT showed better outcomes than conventional interventions on some motor aspects in PD. However, RAGT did not seem superior to control interventions. Further RCTs that examine the effect of RAGT on more specific outcomes and at different medication statuses are required.