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JAMA Sep 2023Sedentary behavior is associated with cardiometabolic disease and mortality, but its association with dementia is unclear.
IMPORTANCE
Sedentary behavior is associated with cardiometabolic disease and mortality, but its association with dementia is unclear.
OBJECTIVE
To investigate whether accelerometer-assessed sedentary behavior is associated with incident dementia.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective study of prospectively collected data from the UK Biobank including 49 841 adults aged 60 years or older without a diagnosis of dementia at the time of wearing the wrist accelerometer and living in England, Scotland, or Wales. Follow-up began at the time of wearing the accelerometer (February 2013 to December 2015) and continued until September 2021 in England, July 2021 in Scotland, and February 2018 in Wales.
EXPOSURES
Mean daily sedentary behavior time (included in the primary analysis) and mean daily sedentary bout length, maximum daily sedentary bout length, and mean number of daily sedentary bouts (included in the secondary analyses) were derived from a machine learning-based analysis of 1 week of wrist-worn accelerometer data.
MAIN OUTCOME AND MEASURES
Incident all-cause dementia diagnosis from inpatient hospital records and death registry data. Cox proportional hazard models with linear and cubic spline terms were used to assess associations.
RESULTS
A total of 49 841 older adults (mean age, 67.19 [SD, 4.29] years; 54.7% were female) were followed up for a mean of 6.72 years (SD, 0.95 years). During this time, 414 individuals were diagnosed with incident all-cause dementia. In the fully adjusted models, there was a significant nonlinear association between time spent in sedentary behavior and incident dementia. Relative to a median of 9.27 hours/d for sedentary behavior, the hazard ratios (HRs) for dementia were 1.08 (95% CI, 1.04-1.12, P < .001) for 10 hours/d, 1.63 (95% CI, 1.35-1.97, P < .001) for 12 hours/d, and 3.21 (95% CI, 2.05-5.04, P < .001) for 15 hours/d. The adjusted incidence rate of dementia per 1000 person-years was 7.49 (95% CI, 7.48-7.49) for 9.27 hours/d of sedentary behavior, 8.06 (95% CI, 7.76-8.36) for 10 hours/d, 12.00 (95% CI, 10.00-14.36) for 12 hours/d, and 22.74 (95% CI, 14.92-34.11) for 15 hours/d. Mean daily sedentary bout length (HR, 1.53 [95% CI, 1.03-2.27], P = .04 and 0.65 [95% CI, 0.04-1.57] more dementia cases per 1000 person-years for a 1-hour increase from the mean of 0.48 hours) and maximum daily sedentary bout length (HR, 1.15 [95% CI, 1.02-1.31], P = .02 and 0.19 [95% CI, 0.02-0.38] more dementia cases per 1000 person-years for a 1-hour increase from the mean of 1.95 hours) were significantly associated with higher risk of incident dementia. The number of sedentary bouts per day was not associated with higher risk of incident dementia (HR, 1.00 [95% CI, 0.99-1.01], P = .89). In the sensitivity analyses, after adjustment for time spent in sedentary behavior, the mean daily sedentary bout length and the maximum daily sedentary bout length were no longer significantly associated with incident dementia.
CONCLUSIONS AND RELEVANCE
Among older adults, more time spent in sedentary behaviors was significantly associated with higher incidence of all-cause dementia. Future research is needed to determine whether the association between sedentary behavior and risk of dementia is causal.
Topics: Aged; Female; Humans; Male; Dementia; England; Retrospective Studies; Sedentary Behavior; Accelerometry; Incidence; Middle Aged; United Kingdom; Registries
PubMed: 37698563
DOI: 10.1001/jama.2023.15231 -
JAMA Jun 2023Prior studies have suggested that transgender individuals may be a high-risk group with respect to suicide attempt and mortality, but large-scale, population-based...
IMPORTANCE
Prior studies have suggested that transgender individuals may be a high-risk group with respect to suicide attempt and mortality, but large-scale, population-based investigations are lacking.
OBJECTIVE
To examine in a national setting whether transgender individuals have higher rates of suicide attempt and mortality than nontransgender individuals.
DESIGN, SETTING, AND PARTICIPANTS
Nationwide, register-based, retrospective cohort study on all 6 657 456 Danish-born individuals aged 15 years or older who lived in Denmark between January 1, 1980, and December 31, 2021.
EXPOSURE
Transgender identity was determined through national hospital records and administrative records of legal change of gender.
MAIN OUTCOMES AND MEASURES
Suicide attempts, suicide deaths, nonsuicidal deaths, and deaths by any cause during 1980 through 2021 were identified in national hospitalization and causes of death registers. Adjusted incidence rate ratios (aIRRs) with 95% CIs controlling for calendar period, sex assigned at birth, and age were calculated.
RESULTS
The 6 657 456 study participants (50.0% assigned male sex at birth) were followed up during 171 023 873 person-years. Overall, 3759 individuals (0.06%; 52.5% assigned male sex at birth) were identified as transgender at a median age of 22 years (IQR, 18-31 years) and followed up during 21 404 person-years, during which 92 suicide attempts, 12 suicides, and 245 suicide-unrelated deaths occurred. Standardized suicide attempt rates per 100 000 person-years were 498 for transgender vs 71 for nontransgender individuals (aIRR, 7.7; 95% CI, 5.9-10.2). Standardized suicide mortality rates per 100 000 person-years were 75 for transgender vs 21 for nontransgender individuals (aIRR, 3.5; 95% CI, 2.0-6.3). Standardized suicide-unrelated mortality rates per 100 000 person-years were 2380 for transgender vs 1310 for nontransgender individuals (aIRR, 1.9; 95% CI, 1.6-2.2), and standardized all-cause mortality rates per 100 000 person-years were 2559 for transgender vs 1331 for nontransgender individuals (aIRR, 2.0; 95% CI, 1.7-2.4). Despite declining rates of suicide attempts and mortality during the 42 years covered, aIRRs remained significantly elevated in recent calendar periods up to and including 2021 for suicide attempts (aIRR, 6.6; 95% CI, 4.5-9.5), suicide mortality (aIRR, 2.8; 95% CI, 1.3-5.9), suicide-unrelated mortality (aIRR, 1.7; 95% CI, 1.5-2.1), and all-cause mortality (aIRR, 1.7; 95% CI, 1.4-2.1).
CONCLUSIONS AND RELEVANCE
In this Danish population-based, retrospective cohort study, results suggest that transgender individuals had significantly higher rates of suicide attempt, suicide mortality, suicide-unrelated mortality, and all-cause mortality compared with the nontransgender population.
Topics: Adolescent; Adult; Humans; Male; Young Adult; Denmark; Hospitalization; Retrospective Studies; Suicide, Attempted; Transgender Persons; Gender Identity; Registries; Suicide; Female
PubMed: 37367977
DOI: 10.1001/jama.2023.8627 -
The Lancet. Respiratory Medicine Jul 2023Bronchiectasis is a heterogeneous, neglected disease with few multicentre studies exploring the causes, severity, microbiology, and treatment of the disease across... (Observational Study)
Observational Study
BACKGROUND
Bronchiectasis is a heterogeneous, neglected disease with few multicentre studies exploring the causes, severity, microbiology, and treatment of the disease across Europe. This aim of this study was to describe the clinical characteristics of bronchiectasis and compare between different European countries.
METHODS
EMBARC is an international clinical research network for bronchiectasis. We report on a multicentre, prospective, observational, non-interventional, cohort study (the EMBARC registry) conducted across 27 European countries and Israel. Comprehensive clinical data were collected from adult patients (aged ≥18 years) at baseline and annual follow-up visits using electronic case report form. Data from individual countries were grouped into four regions (the UK, northern and western Europe, southern Europe, and central and eastern Europe according to modified EU EuroVoc classification). Follow-up data were used to explore differences in exacerbation frequency between regions using a negative binomial regression model.
FINDINGS
Between Jan 12, 2015, and April 12, 2022, 16 963 individuals were enrolled. Median age was 67 years (IQR 57-74), 10 335 (60·9%) participants were female and 6628 (39·1%) were male. The most common cause of bronchiectasis in all 16 963 participants was post-infective disease in 3600 (21·2%); 6466 individuals (38·1%) were classified as idiopathic. Individuals with bronchiectasis experienced a median of two exacerbations (IQR 1-4) per year and 4483 (26·4%) patients had a hospitalisation for exacerbation in the previous year. When examining the percentage of all isolated bacteria, marked differences in microbiology were seen between countries, with a higher frequency of Pseudomonas aeruginosa and lower Haemophilus influenzae frequency in southern Europe, compared with higher H influenzae in the UK and northern and western Europe. Compared with other regions, patients in central and eastern Europe had more severe bronchiectasis measured by the Bronchiectasis Severity Index (51·3% vs 35·1% in the overall cohort) and more exacerbations leading to hospitalisations (57·9% vs 26·4% in the overall cohort). Overall, patients in central and eastern Europe had an increased frequency of exacerbations (adjusted rate ratio [RR] 1·12, 95% CI 1·01-1·25) and a higher frequency of exacerbations leading to hospitalisations (adjusted RR 1·71, 1·44-2·02) compared with patients in other regions. Treatment of bronchiectasis was highly heterogeneous between regions.
INTERPRETATION
Bronchiectasis shows important geographical variation in causes, microbiology, severity, and outcomes across Europe.
FUNDING
European Union-European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative.
TRANSLATIONS
For the Arabic, French, German, Greek, Hebrew, Irish, Russian and Spanish translations of the abstract see Supplementary Materials section.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Bronchiectasis; Cohort Studies; Disease Progression; Europe; Prospective Studies; Registries
PubMed: 37105206
DOI: 10.1016/S2213-2600(23)00093-0 -
Journal of Neurology Aug 2023Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in...
Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis.
OBJECTIVE
Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).
METHODS
Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.
RESULTS
As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.
CONCLUSION
Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
Topics: Humans; Codon, Nonsense; Muscular Dystrophy, Duchenne; Registries; Disease Progression
PubMed: 37115359
DOI: 10.1007/s00415-023-11687-1 -
Ugeskrift For Laeger Jan 2024Studies on cancer loci by use of twin data reveal sources of variation in risk. The Nordic twin and cancer registries contain the largest cohort of population...
Studies on cancer loci by use of twin data reveal sources of variation in risk. The Nordic twin and cancer registries contain the largest cohort of population representative twins ever studied with more than median 40 years of follow-up. This article considers findings that show influences on familial risk and demonstrates the strengths of the matched case co-twin design for unraveling important risk factors of cancers. Studies using twin data will expectedly continue to provide insights into cancer epidemiology and genetics for the benefit of prevention and treatment.
Topics: Humans; Diseases in Twins; Neoplasms; Registries; Risk Factors; Twin Studies as Topic
PubMed: 38305325
DOI: 10.61409/V11230732 -
Brain : a Journal of Neurology Dec 2023The capacity and power of data from cohorts, registries and randomized trials to provide answers to contemporary clinical questions in neurology has increased... (Review)
Review
The capacity and power of data from cohorts, registries and randomized trials to provide answers to contemporary clinical questions in neurology has increased considerably over the past two decades. Novel sophisticated statistical methods are enabling us to harness these data to guide treatment decisions, but their complexity is making appraisal of clinical evidence increasingly demanding. In this review, we discuss several methodological aspects of contemporary research of treatment effectiveness in observational data in neurology, aimed at academic neurologists and analysts specializing in outcomes research. The review discusses specifics of the sources of observational data and their key features. It focuses on the limitations of observational data and study design, as well as statistical approaches aimed to overcome these limitations. Among the examples of leading clinical themes typically studied with analyses of observational data, the review discusses methodological approaches to comparative treatment effectiveness, development of diagnostic criteria and definitions of clinical outcomes. Finally, this review provides a brief summary of key points that will help clinical audience critically evaluate design and analytical aspects of studies of disease outcomes using observational data.
Topics: Humans; Treatment Outcome; Outcome Assessment, Health Care; Registries; Research Design; Neurology
PubMed: 37587541
DOI: 10.1093/brain/awad278 -
Arquivos de Neuro-psiquiatria Aug 2023Evaluation and treatment of primary and secondary headaches is a global public health challenge. Recognizing the epidemiological impact of headaches, a group of... (Observational Study)
Observational Study
BACKGROUND
Evaluation and treatment of primary and secondary headaches is a global public health challenge. Recognizing the epidemiological impact of headaches, a group of researchers linked to the Brazilian Headache Society proposed the Brazilian Headache Registry and drew up its initial protocol.
OBJECTIVE
Here we describe the methods and preliminary data obtained from the pilot study.
METHODS
This was a multicenter longitudinal observational study conducted between September 2020 and August 2021. Prospective data were collected in three specialist centers for headache care in states in southern and southeastern Brazil. Patients aged 18 years or older who sought care for headache in tertiary centers and who agreed to participate in the study, were considered eligible.
RESULTS
Sixty-six patients were included in the pilot study: 43 (65%) from Rio Grande do Sul state and 23 (35%) from Minas Gerais state. Overall, 90% were female, and the subjects' mean age was 38.2 ± 11.2 years. Primary headaches accounted for 85.3% of the diagnoses made. Among secondary headaches, medication overuse headache was the most frequent type (7.1%).
CONCLUSIONS
The pilot study showed the feasibility of the research protocol developed for tertiary centers. The Brazilian Headache Registry will form a source of longitudinal data with the aim of contributing to better characterization of the various phenotypes of patients with primary and secondary headaches, and to detailing the use of health resources and identifying predictors of better clinical outcomes.
Topics: Female; Male; Humans; Pilot Projects; Brazil; Preliminary Data; Prospective Studies; Headache; Registries
PubMed: 37604204
DOI: 10.1055/s-0043-1771175 -
Advances in Therapy Sep 2023Tyrosine-kinase inhibitors (TKIs) have become the standard treatment for patients with advanced gastrointestinal stromal tumor (GIST); however, secondary mutations can...
INTRODUCTION
Tyrosine-kinase inhibitors (TKIs) have become the standard treatment for patients with advanced gastrointestinal stromal tumor (GIST); however, secondary mutations can still drive disease progression. Studies have shown that ripretinib, a novel switch-control TKI, inhibits various primary and secondary drug-resistant mutations. There is a paucity of data on the effectiveness and safety of ripretinib in a real-world setting. This prospective, large-scale, real-world registry study aimed to evaluate the effectiveness and safety of ripretinib as a fourth-line treatment in Chinese patients with advanced GIST.
METHODS
Patients ≥ 18 years of age having recurrent/metastatic GIST were enrolled. Key endpoints were median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) incidence. Univariate and multivariate analyses were conducted to identify various parameters associated with PFS.
RESULTS
A total of 240 patients were enrolled. After a median follow-up period of 6.5 months, the mPFS [95% confidence interval (CI)] was 7.70 (6.60, 8.60) months and the mOS was not reached. Multivariate analysis revealed association of Eastern Cooperative Oncology Group (ECOG) performance status score with PFS and superior benefits for non-gastric was observed as compared to gastric GISTs [hazard ratio (HR) 0.58, 95% CI (0.39-0.86)]. Disease control rate and tumor shrinkage (any magnitude) was 73% and 43%, respectively. Ripretinib was also effective in the subgroup of patients with different gene mutations. The toxicities were tolerable, and most reported AEs were alopecia (17.1%) and hand-foot syndrome (15.4%).
CONCLUSION
Ripretinib demonstrated effectiveness and a tolerable safety profile, making it a viable option as a fourth- or later-line treatment in Chinese patients with advanced GISTs, especially for non-gastric GISTs.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT05697107.
Topics: Humans; Gastrointestinal Stromal Tumors; Neoplasm Recurrence, Local; Registries; Prospective Studies
PubMed: 37356078
DOI: 10.1007/s12325-023-02576-0 -
Journal of the American Heart... Jun 2023Background Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden... (Observational Study)
Observational Study
Background Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision-making model. However, the impact and outcomes of this strategy remain unknown. Methods The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life-threatening cardiovascular conditions. The study will assess sports eligibility decision-making, exercise habits, psychosocial well-being, and long-term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to <35 years diagnosed with a confirmed cardiovascular condition or borderline finding with potential increased risk of major adverse cardiovascular events are eligible. Outcomes will be monitored for an initial 5-year follow-up period or until age 35, and metrics of psychosocial well-being and composite adverse cardiovascular events including arrhythmias, sudden cardiac arrest/sudden cardiac death, and evidence of disease progression will be compared among athletes who continue versus discontinue competitive sports participation. Conclusions The ORCCA study aims to assess the process and results of return to sport decision-making and to monitor major adverse cardiovascular events, exercise habits, and the psychosocial well-being among young competitive athletes diagnosed with confirmed cardiovascular conditions or borderline findings with potential increased risk of major adverse cardiovascular events. The results of this work will generate an evidence base to inform future guidelines.
Topics: Humans; Prospective Studies; Heart Diseases; Athletes; Death, Sudden, Cardiac; Registries
PubMed: 37259981
DOI: 10.1161/JAHA.122.029052 -
Estonian National Mental Health Study: Design and methods for a registry-linked longitudinal survey.Brain and Behavior Aug 2023The Estonian National Mental Health Study (EMHS) was conducted in 2021-2022 to provide population-wide data on mental health in the context of COVID-19 pandemic. The...
OBJECTIVES
The Estonian National Mental Health Study (EMHS) was conducted in 2021-2022 to provide population-wide data on mental health in the context of COVID-19 pandemic. The main objective of this paper is to describe the rationale, design, and methods of the EMHS and to evaluate the survey response.
METHODS
Regionally representative stratified random sample of 20,000 persons aged 15 years and older was drawn from the Estonian Population Register for the study. Persons aged 18 years and older at the time of the sampling were enrolled into three survey waves where they were invited to complete an online or postal questionnaire about mental well-being and disorders, and behavioral, cognitive, and other risk factors. Persons younger than 18 years of age were invited to fill an anonymous online questionnaire starting from wave 2. To complement and validate survey data, data on socio-demographic, health-related, and environmental variables were collected from six national administrative databases and registries. Additionally, a subsample was enrolled into a validation study using ecological momentary assessment.
RESULTS
In total, 5636 adults participated in the survey wave 1, 3751 in wave 2, and 4744 in wave 3. Adjusted response rates were 30.6%, 21.1%, and 27.6%, respectively. Women and older age groups were more likely to respond. Throughout the three survey waves, a considerable share of adult respondents screened positive for depression (27.6%, 25.1%, and 25.6% in waves 1, 2, and 3, respectively). Women and young adults aged 18 to 29 years had the highest prevalence of depression symptoms.
CONCLUSIONS
The registry-linked longitudinal EMHS dataset comprises a rich and trustworthy data source to allow in-depth analysis of mental health outcomes and their correlates among the Estonian population. The study serves as an evidence base for planning mental health policies and prevention measures for possible future crises.
Topics: Young Adult; Humans; Female; Aged; Adolescent; Mental Health; COVID-19; Pandemics; Estonia; Longitudinal Studies; Registries
PubMed: 37278143
DOI: 10.1002/brb3.3106