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BACKGROUND: Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington's Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes. OBJECTIVE: Investigate time to the event of functional decline (HD-ISS Stage 3) as an endpoint for trials in HD and present sample size estimates after enrichment. METHODS: We classified individuals from observational studies according to the HD-ISS. We assessed the ability of the prognostic index normed (PIN) and its components to predict time to HD-ISS Stage 3. For enrichment, we formed groups from deciles of the baseline PIN distribution for HD-ISS Stage 2 participants. We selected enrichment subgroups closer to Stage 3 transition and estimated sample sizes, using delay in the transition time as the effect size. RESULTS: In predicting time to HD-ISS Stage 3, PIN outperforms its components. Survival curves for each PIN decile show that groups with PIN from 1.48 to 2.74 have median time to Stage 3 of approximately 2 years and these are combined to create enrichment subgroups. Sample size estimates are presented by enrichment subgroup. CONCLUSIONS: PIN is predictive of functional decline. A delay of 9 months or more in the transition to Stage 3 for an enriched sample yields feasible sample size estimates, demonstrating that this approach can aid in planning future trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Huntington's disease (HD), due to expansion of a CAG repeat in HTT , is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5'-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.
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Psychiatric disorders affect millions of people globally, representing a major public health challenge. Adherence to medication treatment is essential for the effective management of these disorders, but non-adherence rates are variable and worrying. Several factors, such as concerns about side effects, lack of knowledge about the disease, treatment costs and fear of dependence, are associated with non-adherence. This study explores the importance of patient autonomy in mental health, highlighting patient-centered strategies to improve treatment adherence. The need for innovative practices that empower patients is emphasized, promoting active and informed participation in treatment decisions, aiming to improve quality of life and therapeutic results.
Os transtornos psiquiátricos afetam milhões de pessoas globalmente, representando um grande desafio para a saúde pública. A adesão ao tratamento medicamentoso é fundamental para o manejo eficaz desses transtornos, mas as taxas de não adesão são variáveis e preocupantes. Diversos fatores, como preocupações com efeitos colaterais, desconhecimento sobre a doença, custos do tratamento e medo de dependência, estão associados à não adesão. Este estudo explora a importância da autonomia do paciente na saúde mental, destacando estratégias centradas no paciente para melhorar a adesão ao tratamento. Enfatiza-se a necessidade de práticas inovadoras que empoderem os pacientes, promovendo uma participação ativa e informada nas decisões de tratamento, visando melhorar a qualidade de vida e os resultados terapêuticos.
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INTRODUCTION: Current evidence suggests the potential heightened vulnerability of smokers to severe coronavirus disease (COVID-19) outcomes. AIMS: This study aimed to analyze the clinical outcomes and mortality related to tobacco use in a cohort of hospitalized Brazilian COVID-19 patients. METHODS: This retrospective cohort study analyzed adults hospitalized for COVID-19 in Brazil using the SIVEP-Gripe database (official data reported by public and private healthcare facilities for monitoring severe acute respiratory syndrome cases in Brazil). The inclusion criteria were patients over 18 years of age with a positive RT-qPCR test for SARS-CoV-2. The analysis focused on in-hospital mortality, considering smoking as an exposure variable, and included covariates such as age, gender, and comorbidities. Smoking history was collected from the self-reported field in the database. Statistical analyses included descriptive statistics, crude Odds Ratios, and multivariable binary logistic regression. RESULTS: This study included 2,124,285 COVID-19 patients, among whom 44,774 (2.1 %) were smokers. The average age of the smokers was higher than that of the never-smokers (65.3 years vs. 59.7 years). The clinical outcomes revealed that smokers had higher rates of intensive care unit admission (51.6 % vs. 37.2 % for never-smokers), invasive ventilatory support (31.5 % vs. 20.2 % for never-smokers), and higher mortality (42.7 % vs. 31.8 % for never smokers). In the multivariable analysis, smokers demonstrated a heightened risk of death (aOR 1.23; 95 % CI 1.19-1.25). CONCLUSIONS: This large populational-based cohort study confirms the current evidence and underscore the critical importance of recognizing smoking as a substantial risk factor for adverse outcomes in COVID-19 patients.
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COVID-19 , Mortalidad Hospitalaria , Fumar , Humanos , COVID-19/mortalidad , Brasil/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Fumar/epidemiología , Estudios de Cohortes , SARS-CoV-2 , Factores de Riesgo , Hospitalización/estadística & datos numéricos , Comorbilidad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricosRESUMEN
Quilombolas are ethnic-racial groups, of black ancestry, and had their territories consolidated in Brazil in regions with difficult access and far from large centers. The objective of this study is to know the therapeutic itinerary (IT) adopted by quilombola women in traditional communities located in the North of the state of Minas Gerais. This is a qualitative study with the theoretical model using the Arthur Kleinman health care system. The study scenario was 23 quilombola communities in northern Minas Gerais. Forty quilombola women aged between 25 and 89 years were interviewed. Data analysis was performed following the IT. Units of analysis emerged that were grouped into three categories: quilombola women and the meaning of health and care; the professional care system in quilombola communities; and route of care in situations experienced by women. The therapeutic itinerary of the communities is mainly related to the actions of popular medicine. It was also possible to observe that there are weaknesses in relation to health care due to factors such as difficulty of access to institutionalized services.
Os quilombolas são grupos étnico-raciais de ancestralidade negra e tiveram seus territórios consolidados no Brasil em regiões com acesso difícil e distante dos grandes centros. O objetivo desse estudo é conhecer o itinerário terapêutico (IT) adotado por mulheres quilombolas em comunidades tradicionais localizadas no norte do estado de Minas Gerais. Trata-se de um estudo com abordagem qualitativa com o modelo teórico utilizando o sistema de cuidados à saúde de Arthur Kleinman. O estudo se deu em 23 comunidades quilombolas do norte de Minas Gerais. Foram entrevistadas 40 mulheres quilombolas, com idades entre 25 e 89 anos. A análise dos dados foi realizada seguindo os IT. Emergiram unidades de análise que foram agrupadas em três categorias: as mulheres quilombolas e o significado da saúde e do cuidado; o sistema de cuidado profissional nas comunidades quilombolas; e itinerário de cuidados nas situações vivenciadas pelas mulheres. O itinerário terapêutico das comunidades se mostra relacionado principalmente às ações de medicina popular. Foi possível observar ainda que existem fragilidades em relação à atenção à saúde devido a fatores como dificuldade de acesso aos serviços institucionalizados.
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Medicina , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Brasil , Análisis de Datos , Instituciones de Salud , Investigación CualitativaRESUMEN
This article aimed to map therapeutic itineraries in health care within rural Quilombola communities in the north of Minas Gerais, Brazil. This is a section of a qualitative research conducted in six visited communities. The data was collected through 18 individual interviews, analyzed using the theoretical-methodological framework of Therapeutic Itineraries, and organized into three empirical themes. The narratives allowed for understanding the paths taken in health care by the Quilombola population, identifying the components of the popular subsystem (natural resources, the use of teas and home remedies), the family subsystem (transmission of knowledge and cultural heritage of care), and the professional subsystem (hospital level, medical care, primary and specialized attention). The difficulties of access are not only due to geographical distances, but also broader aspects of social determination, such as institutional racism, low availability of services, the need for payment for transportation and medical procedures. In this sense, it is necessary to have an approach and interventions from public policies to address ethnic-racial, economic, and access inequalities in health care services.
Este artigo teve como objetivo mapear os itinerários terapêuticos no cuidado em saúde em comunidades quilombolas rurais no norte de Minas Gerais, Brasil. Trata-se de um recorte de uma pesquisa qualitativa realizada em seis comunidades visitadas. Os dados foram produzidos por meio de 18 entrevistas individuais, analisados pelo referencial teórico-metodológico dos itinerários terapêuticos e organizados em três temas empíricos. As narrativas permitiram a compreensão dos percursos trilhados no cuidado em saúde pela população quilombola, a identificação dos componentes do subsistema popular (recursos naturais, o uso de chás e remédios caseiros), do subsistema familiar (transmissão de conhecimentos e herança cultural de cuidados), e do subsistema profissional (nível hospitalar, cuidados médicos, atenção primária e especializada). As dificuldades de acesso não decorrem apenas das distâncias geográficas, envolvem aspectos mais amplos da determinação social, como o racismo institucional, a baixa oferta de serviços, a necessidade de pagamento para deslocamentos e procedimentos médicos. Nesse sentido, fazem-se necessárias uma abordagem e intervenções das políticas públicas frente às desigualdades étnico-raciais, econômicas e de acesso aos serviços de cuidado em saúde.
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Instituciones de Salud , Hospitales , Humanos , Brasil , Geografía , Atención a la SaludRESUMEN
Background: Understanding the sensitivity and utility of clinical assessments across different HD stages is important for study/trial endpoint selection and clinical assessment development. The Integrated HD Progression Model (IHDPM) characterizes the complex symptom progression of HD and separates the disease into nine ordered disease states. Objective: To generate a temporal map of discriminatory clinical measures across the IHDPM states. Methods: We applied the IHDPM to all HD individuals in an integrated longitudinal HD dataset derived from four observational studies, obtaining disease state assignment for each study visit. Using large-scale screening, we estimated Cohen's effect sizes to rank the discriminative power of 2,472 clinical measures for separating observations in disease state pairs. Individual trajectories through IHDPM states were examined. Discriminative analyses were limited to individuals with observations in both states of the pairs compared (N = 3,790). Results: Discriminative clinical measures were heterogeneous across the HD life course. UHDRS items were frequently identified as the best state pair discriminators, with UHDRS Motor items - most notably TMS - showing the highest discriminatory power between the early-disease states and early post-transition period states. UHDRS functional items emerged as strong discriminators from the transition period and on. Cognitive assessments showed good discriminative power between all state pairs examined, excepting state 1 vs. 2. Several non-UHDRS assessments were also flagged as excellent state discriminators for specific disease phases (e.g., SF-12). For certain state pairs, single assessment items other than total/summary scores were highlighted as having excellent discriminative power. Conclusion: By providing ranked quantitative scores indicating discriminatory ability of thousands of clinical measures between specific pairs of IHDPM states, our results will aid clinical trial designers select the most effective outcome measures tailored to their study cohort. Our observations may also assist in the development of end points targeting specific phases in the disease life course, through providing specific conceptual foci.
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ABSTRACT BACKGROUND: Precisely determining the aspects related to an instrument's validity and reliability measures allows for greater assurance of the quality of the results. OBJECTIVES: To analyze the psychometric properties of The Providers Survey in the Brazilian context of mental health services. DESIGN AND SETTING: The instrument validation study was conducted in Montes Claros, Minas Gerais, Brazil. METHODS: The validation study was conducted using the Consensus-based Standards for the Selection of Health Measurement Instruments checklist to analyze its validity and reliability. RESULTS: A committee of expert judges performed content validation after which the Content Validity Index was calculated. Construct validation took place through Exploratory Factor Analysis using the Kaiser-Meyer-Olkin Test criterion and Bartlett's Sphericity Test. Reliability was verified using test-retest reliability. The significance level adopted for the statistical tests was 5% (P < 0.05). The final instrument comprised 54 questions. The Content Validity Index was 97%. Exploratory Factor Analysis identified a Kaiser-Meyer-Olkin index of 0.901 and Bartlett's Sphericity Test with P < 0.001. We obtained a Cronbach's alpha coefficient of 0.95 and an intraclass correlation coefficient of 0.849. CONCLUSIONS: The Providers Survey, translated and adapted into Portuguese, was named the Work Assessment Instrument for the Recovery of Mental Health. It presented adequate psychometric properties for evaluating work-related practices for the recovery of psychosocial care network users.
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Resumo Os quilombolas são grupos étnico-raciais de ancestralidade negra e tiveram seus territórios consolidados no Brasil em regiões com acesso difícil e distante dos grandes centros. O objetivo desse estudo é conhecer o itinerário terapêutico (IT) adotado por mulheres quilombolas em comunidades tradicionais localizadas no norte do estado de Minas Gerais. Trata-se de um estudo com abordagem qualitativa com o modelo teórico utilizando o sistema de cuidados à saúde de Arthur Kleinman. O estudo se deu em 23 comunidades quilombolas do norte de Minas Gerais. Foram entrevistadas 40 mulheres quilombolas, com idades entre 25 e 89 anos. A análise dos dados foi realizada seguindo os IT. Emergiram unidades de análise que foram agrupadas em três categorias: as mulheres quilombolas e o significado da saúde e do cuidado; o sistema de cuidado profissional nas comunidades quilombolas; e itinerário de cuidados nas situações vivenciadas pelas mulheres. O itinerário terapêutico das comunidades se mostra relacionado principalmente às ações de medicina popular. Foi possível observar ainda que existem fragilidades em relação à atenção à saúde devido a fatores como dificuldade de acesso aos serviços institucionalizados.
Abstract Quilombolas are ethnic-racial groups, of black ancestry, and had their territories consolidated in Brazil in regions with difficult access and far from large centers. The objective of this study is to know the therapeutic itinerary (IT) adopted by quilombola women in traditional communities located in the North of the state of Minas Gerais. This is a qualitative study with the theoretical model using the Arthur Kleinman health care system. The study scenario was 23 quilombola communities in northern Minas Gerais. Forty quilombola women aged between 25 and 89 years were interviewed. Data analysis was performed following the IT. Units of analysis emerged that were grouped into three categories: quilombola women and the meaning of health and care; the professional care system in quilombola communities; and route of care in situations experienced by women. The therapeutic itinerary of the communities is mainly related to the actions of popular medicine. It was also possible to observe that there are weaknesses in relation to health care due to factors such as difficulty of access to institutionalized services.
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Resumo Este artigo teve como objetivo mapear os itinerários terapêuticos no cuidado em saúde em comunidades quilombolas rurais no norte de Minas Gerais, Brasil. Trata-se de um recorte de uma pesquisa qualitativa realizada em seis comunidades visitadas. Os dados foram produzidos por meio de 18 entrevistas individuais, analisados pelo referencial teórico-metodológico dos itinerários terapêuticos e organizados em três temas empíricos. As narrativas permitiram a compreensão dos percursos trilhados no cuidado em saúde pela população quilombola, a identificação dos componentes do subsistema popular (recursos naturais, o uso de chás e remédios caseiros), do subsistema familiar (transmissão de conhecimentos e herança cultural de cuidados), e do subsistema profissional (nível hospitalar, cuidados médicos, atenção primária e especializada). As dificuldades de acesso não decorrem apenas das distâncias geográficas, envolvem aspectos mais amplos da determinação social, como o racismo institucional, a baixa oferta de serviços, a necessidade de pagamento para deslocamentos e procedimentos médicos. Nesse sentido, fazem-se necessárias uma abordagem e intervenções das políticas públicas frente às desigualdades étnico-raciais, econômicas e de acesso aos serviços de cuidado em saúde.
Abstract This article aimed to map therapeutic itineraries in health care within rural Quilombola communities in the north of Minas Gerais, Brazil. This is a section of a qualitative research conducted in six visited communities. The data was collected through 18 individual interviews, analyzed using the theoretical-methodological framework of Therapeutic Itineraries, and organized into three empirical themes. The narratives allowed for understanding the paths taken in health care by the Quilombola population, identifying the components of the popular subsystem (natural resources, the use of teas and home remedies), the family subsystem (transmission of knowledge and cultural heritage of care), and the professional subsystem (hospital level, medical care, primary and specialized attention). The difficulties of access are not only due to geographical distances, but also broader aspects of social determination, such as institutional racism, low availability of services, the need for payment for transportation and medical procedures. In this sense, it is necessary to have an approach and interventions from public policies to address ethnic-racial, economic, and access inequalities in health care services.
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Considerando os desafios à reabilitação psicossocial, objetivou-se compreender a perspectiva de usuários e trabalhadores no tratamento psicofarmacológico. Trata-se de um estudo qualitativo que entrevistou seis profissionais e dez usuários do Centro de Atenção Psicossocial de um município da região norte de Minas Gerais. As transcrições foram tratadas em Ciclos de Codificação e examinadas pela Análise de Discurso. Definiram-se três categorias relativas à dimensão micropolítica do cuidado: o fluxograma institucional, os espaços intercessores e a produção subjetiva dos agentes. Revelaram-se dissonâncias entre enunciados alusivos à política da atenção psicossocial, com a concorrência de concepções e tecnologias de cuidado emancipatórias e restritivas. Constatou-se a importância da análise micropolítica do cuidado no tratamento psicofarmacológico, favorecendo os processos de contratualidade, protagonismo e autonomia do usuário.
Considerando los desafíos para la rehabilitación psicosocial, el objetivo fue comprender la perspectiva de usuarios y trabajadores en el tratamiento psicofarmacéutico. Se trata de un estudio cualitativo que entrevistó a seis profesionales y a diez usuarios del Centro de Atención Psicosocial de un municipio de la región norte de Minas Gerais. Las transcripciones fueron tratadas en Ciclos de Codificación y examinadas por el Análisis del Discurso. Se definieron tres categorías relativas a la dimensión micropolítica del cuidado: el diagrama de flujo institucional, los espacios intercesores y la producción subjetiva de los agentes. Se revelaron disonancias entre enunciados alusivos a la política de la atención psicosocial, con la concurrencia de concepciones y tecnologías de cuidado emancipatorias y restrictivas. Se constató la importancia del análisis micropolítico del cuidado en el tratamiento psicofarmacéutico, favoreciendo los procesos de contractualidad, protagonismo y autonomía del usuario.
Considering the challenges to psychosocial rehabilitation, this study was aimed at understanding the perspective of users and workers regarding psychopharmacological treatment. This is a qualitative study, which interviewed six providers and ten users of the Psychosocial Care Center of a municipality in the north of Minas Gerais. The transcripts were treated in Coding Cycles and examined by Discourse Analysis. Three categories related to the micropolitical dimension of care were defined: the institutional flowchart; the intercessory spaces; and the subjective production of the agents. Dissonances were revealed between statements alluding to the psychosocial care policy, with the competition of emancipatory and restrictive conceptions and technologies of care. The importance of the micropolitical analysis of care in psychopharmacological treatment was verified, favoring the processes of contractuality, protagonism, and user autonomy.
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O estudo objetivou mapear as estratégias utilizadas para o trabalho colaborativo em equipes de Saúde da Família (eSF) inseridas na Atenção Primária à Saúde (APS), em um município do norte de Minas. Trata-se de um estudo qualitativo, com a proposta metodológica da Cartografia. Os dados foram produzidos em quatro eSF por meio de observação participante, questionário de identificação, diário cartográfico, entrevista semiestruturada individual e grupo focal. A análise do discurso e o rastreio cartográfico possibilitaram a construção de duas categorias temáticas e um mapa cartográfico. Alcançou-se que as estratégias, consideradas linhas de fuga, permitem transformações existenciais no trabalho em equipe, pois originam nascentes em solos cristalizados, pensamentos problematizadores, subjetividade e interações disciplinares. Concluiu-se que as linhas duras não devem ser eliminadas do trabalho em equipe, pois coexistem nessa realidade, e o que importa é como são vivenciadas nas relações.
El objetivo del estudio fue mapear las estrategias utilizadas para el trabajo colaborativo en equipos de Salud de la Familia (eSF), inseridas en la Atención Primaria de la Salud, en un municipio del Norte de Minas Gerais. Se trata de un estudio cualitativo, con la propuesta metodológica de la Cartografía. Los datos se produjeron en cuatro eSF, por medio de observación participativa, cuestionario de identificación, diario cartográfico, entrevista semiestructurada individual y grupo focal. El análisis del discurso y el rastreo cartográfico posibilitaron la construcción de dos categorías temáticas y un mapa cartográfico. Se vio que las estrategias, consideradas líneas de fuga, permiten transformaciones en el trabajo en equipo, puesto que originan manantiales en suelos cristalizados, pensamientos problematizadores, subjetividad e interacciones disciplinarias. Se concluyó que las líneas duras no deben eliminarse del trabajo en equipo, puesto que coexisten en esta realidad y lo que importa es cómo se experimentan en las relaciones.
The study aimed to map the strategies used for collaborative work in Family Health Teams (FHT), inserted in Primary Health Care, in a municipality in the North of Minas. This is a qualitative study, with the methodological proposal of Cartography. Data were produced in four FHT, through participant observation, identification questionnaire, cartographic diary, semi-structured individual interview and focus group. Discourse analysis and mapping screening enabled the construction of two thematic categories and a cartographic map. It was reached that the strategies, considered lines of flight, allow existential transformations in teamwork, since they originate springs in crystallized soils, problematizing thoughts, subjectivity, and disciplinary interactions. It was concluded that hard lines should not be eliminated from teamwork, for they coexist in this reality, and what matters is how they are experienced in relationships.
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Background and Objectives: The variable CAG repeat expansion in the huntingtin gene and its inverse relationship to motor dysfunction onset are fundamental features of Huntington disease (HD). However, the wider phenotype (including non-motor features) at particular CAG lengths, ages, and functional levels is less well-characterized. The large number of participants in the Enroll-HD observational study enables the development of a phenotype atlas that summarizes the range and distribution of HD phenotypes, including outliers and possible clusters, with respect to various CAG repeat lengths, age ranges, and declining functional levels. Methods: Enroll-HD is an ongoing prospective longitudinal observational study that collects natural history data, releasing periodic data sets, in people with HD (PwHD) and controls. Core assessments at annual visits focus on behavioral, cognitive, motor, and functional status. Periodic data set 5, used for the development of the first iteration of the Enroll-HD Phenotype Atlas (EHDPA), included all eligible data collected through October 31, 2020. The atlas is based on subsets (cells) of descriptive data for all motor, cognitive, psychiatric, and functional measures that are routinely collected at most Enroll-HD sites, analyzed by single CAG lengths and 5-year age blocks. Results: Data from 42,840 visits from 15,982 unique PwHD were available for analysis. At baseline, participants had a mean ± SD age of 48.9 ± 13.9 years and CAG repeat length of 43.4 ± 3.6 and 54.1% were female. The EHDPA includes 223 age-by-CAG subsets for CAG repeats between 36 and 69 with five-year age brackets starting from 20-24 years up to 85-89 years. The atlas can be browsed at enroll-hd.org/for-researchers/atlas-of-hd-phenotype/. Discussion: The EHDPA summarizes the spectrum and distribution of HD phenotypes, including outliers and possible clusters, in all domains of disease involvement for the range of CAG repeat lengths, ages, and functional levels. Its availability in an easy-to-use online format will assist clinicians in tracking disease progression in PwHD by identifying phenotypic features most associated with loss of function and enabling conversations related to prognosis. The observable patterns in the EHDPA should also catalyze more formal multidomain characterization of motor, cognitive, and psychiatric progression and their relationships to functional decline and disease modifiers. Trial Registration Information: Enroll-HD is registered with clinicaltrials.gov: NCT01574053.
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This study aimed to assess the levels of physical activity (PA) among elderly teachers. It was an epidemiological, cross-sectional, and analytical web survey conducted with teachers working in public basic education schools. Data collection took place between October and December 2021 through an online form. The dependent variable was physical activity practice, classifying teachers as either physically active or inactive. Descriptive, bivariate, and multiple analyses were performed using Poisson Regression with robust variance. A total of 1907 teachers participated in the study, of whom 5.6% were elderly, ranging in age from 60 to 72 years. Regarding PA practice, elderly teachers were found to be more physically inactive compared with adult teachers (PR = 1.18; 95% CI = 1.04; 1.34). Conclusion: A statistically significant difference in PA practice was observed between adult and elderly teachers, indicating that elderly teachers are more physically inactive.
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Timelines of events, such as symptom appearance or a change in biomarker value, provide powerful signatures that characterise progressive diseases. Understanding and predicting the timing of events is important for clinical trials targeting individuals early in the disease course when putative treatments are likely to have the strongest effect. However, previous models of disease progression cannot estimate the time between events and provide only an ordering in which they change. Here, we introduce the temporal event-based model (TEBM), a new probabilistic model for inferring timelines of biomarker events from sparse and irregularly sampled datasets. We demonstrate the power of the TEBM in two neurodegenerative conditions: Alzheimer's disease (AD) and Huntington's disease (HD). In both diseases, the TEBM not only recapitulates current understanding of event orderings but also provides unique new ranges of timescales between consecutive events. We reproduce and validate these findings using external datasets in both diseases. We also demonstrate that the TEBM improves over current models; provides unique stratification capabilities; and enriches simulated clinical trials to achieve a power of 80% with less than half the cohort size compared with random selection. The application of the TEBM naturally extends to a wide range of progressive conditions.