Effectiveness of telerehabilitation and home-based falls prevention programs for community-dwelling older adults: a systematic review and meta-analysis protocol.

INTRODUCTION: Falls among older adults are associated with adverse sequelae including fractures, chronic pain and disability, which can lead to loss of independence and increased risks of nursing home admissions. The COVID-19 pandemic has significantly increased the uptake of telehealth, but the effectiveness of virtual, home-based fall prevention programmes is not clearly known. We aim to synthesise the trials on telerehabilitation and home-based falls prevention programmes to determine their effectiveness in reducing falls and adverse outcomes, as well as to describe the safety risks associated with telerehabilitation. METHODS AND ANALYSIS: This protocol was developed using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Database searches from inception to August 2022 will be conducted without language restrictions of MEDLINE, EMBASE, Ovid HealthSTAR, CINAHL, SPORTDiscus, Physiotherapy EvidenceDatabase (PEDro) and the Cochrane Library. Grey literature including major geriatrics conference proceedings will be reviewed. Using Covidence software, two independent reviewers will in duplicate determine the eligibility of randomised controlled trials (RCTs). Eligible RCTs will compare telerehabilitation and home-based fall prevention programmes to usual care among community-dwelling older adults and will report at least one efficacy outcome: falls, fractures, hospitalisations, mortality or quality of life; or at least one safety outcome: pain, myalgias, dyspnoea, syncope or fatigue. Secondary outcomes include functional performance in activities of daily living, balance and endurance. Risk of bias will be assessed using the Cochrane Collaboration tool. DerSimonian-Laird random effects models will be used for the meta-analysis. Heterogeneity will be assessed using the I2 statistic and Cochran's Q statistic. We will assess publication bias using the Egger's test. Prespecified subgroup analyses and univariate meta-regression will be used. ETHICS AND DISSEMINATION: Ethics approval is not required. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022356759.

Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis.

BACKGROUND: Traumatic brain injuries (TBI) among military veterans are increasingly recognized as important causes of both short and long-term neuropsychological dysfunction. However, the association between TBI and the development of dementia is controversial. This systematic review and meta-analysis sought to quantify the risks of all-cause dementia including Alzheimer's diseases and related dementias (ADRD), and to explore whether the relationships are influenced by the severity and recurrence of head injuries. METHODS: Database searches of Medline, Embase, Ovid Healthstar, PubMed and PROSPERO were undertaken from inception to December 2020 and supplemented with grey literature searches without language restrictions. Observational cohort studies examining TBI and incident dementia among veterans were analysed using Dersimonian-Laird random-effects models. RESULTS: Thirteen cohort studies totalling over 7.1 million observations with veterans were included. TBI was associated with an increased risk of all-cause dementia (hazard ratio [HR] = 1.95, 95% confidence interval [CI]: 1.55-2.45), vascular dementia (HR = 2.02, 95% CI: 1.46-2.80), but not Alzheimer's disease (HR = 1.30, 95% CI: 0.88-1.91). Severe and penetrating injuries were associated with a higher risk of all-cause dementia (HR = 3.35, 95% CI: 2.47-4.55) than moderate injuries (HR = 2.82, 95% CI: 1.44-5.52) and mild injuries (HR = 1.91, 95% CI: 1.30-2.80). However, the dose-response relationship was attenuated when additional studies with sufficient data to classify trauma severity were included. CONCLUSION: TBI is a significant risk factor for incident all-cause dementia and vascular dementia. These results need to be interpreted cautiously in the presence of significant heterogeneity.

The Critical Importance of Spatial and Temporal Scales in Designing and Interpreting Immune Cell Migration Assays.

Intravital microscopy and other direct-imaging techniques have allowed for a characterisation of leukocyte migration that has revolutionised the field of immunology, resulting in an unprecedented understanding of the mechanisms of immune response and adaptive immunity. However, there is an assumption within the field that modern imaging techniques permit imaging parameters where the resulting cell track accurately captures a cell's motion. This notion is almost entirely untested, and the relationship between what could be observed at a given scale and the underlying cell behaviour is undefined. Insufficient spatial and temporal resolutions within migration assays can result in misrepresentation of important physiologic processes or cause subtle changes in critical cell behaviour to be missed. In this review, we contextualise how scale can affect the perceived migratory behaviour of cells, summarise the limited approaches to mitigate this effect, and establish the need for a widely implemented framework to account for scale and correct observations of cell motion. We then extend the concept of scale to new approaches that seek to bridge the current "black box" between single-cell behaviour and systemic response.

Use of family disability service by families with young children with disabilities.

AIM: To investigate which families with young children with disabilities used disability services and when they used services to inform policy on service delivery. METHOD: We used linked administrative data from different ministries in Alberta to describe families' use of disability services when their children were between the ages of 3 and 8 years old. Disability was investigated on the basis of the presence of a severe special education code for children, and level of special education code. The outcome was the use of family disability services. RESULTS: Of 31 346 children, 24 761 (79.0%) had no special education code, 3982 (12.7%) had a mild special education code, and 2603 (8.3%) had a severe special education code. Level of special education code was associated with child characteristics and service use. Children with severe special education codes generally were more likely to report service use and have poor outcomes than those with less severe codes. Of note, 26% of children with severe special education codes used family disability services. In addition, among children with severe special education codes, many years of severe coding (compared with fewer years) had the strongest association with family disability service use (prevalence ratio 5.50; 95% confidence interval 4.10-7.37). Associations with family disability service use were seen with mental health, health care, and educational achievement. Interactions between child characteristics and service use were observed. INTERPRETATION: This study provides evidence that families were more likely to use disability services when they were involved with other services, and that use interacts with various factors. The findings highlight the importance of considering service eligibility, referral, and integration.

Health care service for families with children at early risk of developmental delay: an All Our Families cohort study.

AIM: This study examined children's health care service use, mothers' workforce participation, and mothers' community engagement based on children's risk of developmental delay. METHOD: We used data from the All Our Families study, a prospective pregnancy cohort. Ages and Stages Questionnaire (ASQ) scores at year 2 indicated risk of developmental delay. To investigate the impact of risk of developmental delay when children were not diagnosed, a sensitivity analysis excluded reports of neurodevelopmental disorder (NDD) diagnosis at year 3. Outcomes were maternal reports of children's health and allied health visits (and estimated costs), and maternal workforce participation and community engagement from year 2 to 3. RESULTS: Among 1314 mother-child dyads, 209 (16%) children were classified as being at risk of developmental delay by the ASQ, and 42 (3%) had a reported diagnosis of NDD. Risk of developmental delay was related to increased use of allied health care services (incidence risk ratio 5.04 [year 3]; 95% confidence interval 2.49-10.2) and health visits (incidence risk ratio 1.33 [year 3]; 95% confidence interval 1.14-1.54). The average expected allied health costs were greater for children at risk versus not at risk of developmental delay. However, when excluding children with reported diagnoses of an NDD from this analysis, increased service use and costs in the remaining at-risk population were not observed. Community engagement and workplace participation among families did not differ on the basis of risk of developmental delay. INTERPRETATION: These results suggest increased health care service use by families of children at risk of developmental delay is driven by those receiving a diagnosis of an NDD in the subsequent year. WHAT THIS PAPER ADDS: Early developmental delay risk was related to health care service use and costs. Diagnosis of neurodevelopmental disorder drove increased health care service use and costs. Early developmental delay risk did not relate to parental workforce participation. Early developmental delay risk did not relate to community engagement participation.

SERVICIO DE ATENCIÓN MÉDICA PARA FAMILIAS CON NIÑOS EN RIESGO TEMPRANO DE RETRASO EN EL DESARROLLO: UN ESTUDIO DE COHORTE DE TODAS NUESTRAS FAMILIAS: OBJETIVO: Este estudio examinó el uso del servicio de atención médica de los niños en riesgo de retraso en el desarrollo, y a su vez la participación de las madres en el mercado laboral y su participación comunitaria basada en el riesgo de los niños de presentar retraso en el desarrollo. MÉTODO: Utilizamos datos del estudio All Our Families, una cohorte de embarazo longitudinal. Las puntuaciones del Cuestionario de edades y etapas (ASQ) a los 2 años se usaron para identificar riesgo de retraso en el desarrollo. Para investigar el impacto del riesgo de retraso del desarrollo cuando los niños no fueron diagnosticados, un análisis de sensibilidad excluyó los informes de diagnóstico de trastornos del neurodesarrollo (NDD) a los 3 años. Los resultados se recolectaron de informes maternos de salud infantil y visitas de salud a diferentes profesionales de la salud (y costos estimados), y la participación materna en el mercado laboral y la participación materna en la comunidad entre el 2 a 3 año de vida de sus hijos. RESULTADOS: Entre 1.314 díadas madre-hijo, 209 (16%) niños fueron clasificados como en riesgo de retraso en el neurodesarrollo por el ASQ, y 42 (3%) tenían un diagnóstico informado de NDD. El riesgo de retraso en el desarrollo se relacionó con un mayor uso de servicios de atención médica por diversos profesionales de la salud (incidencia cociente de riesgos 5.04 [año 3]; Intervalo de confianza del 95% 2.49-10.2) y visitas de salud (riesgo de incidencia relación 1,33 [año 3]; 95% intervalo de confianza 1.14-1.54). La proyección de los costos promedio de salud aliada esperada fueron mayores para los niños en riesgo versus no en riesgo de retraso en el desarrollo. Sin embargo, al excluir a los niños con diagnósticos informados de un NDD de este análisis, no se observaron un aumento en el uso del servicio y los costos en la población en riesgo restante. Cuando se comparó la participación en la comunidad y la participación en el mercado laboral entre las familias, los resultados no difirieron en función del riesgo de retraso en el desarrollo de los niños. INTERPRETACIÓN: Estos resultados sugieren que el mayor uso de servicios de atención médica por parte de las familias de los niños en riesgo de retraso del desarrollo son impulsados por aquellos que reciben un diagnóstico de NDD en el año siguiente.

SERVIÇOS DE SAÚDE PARA FAMÍLIAS COM CRIANÇAS EM RISCO PRECOCE PARA ATRASO NO DESENVOLVIMENTO: UM ESTUDO DE COORTE TODAS AS NOSSAS FAMÍLIAS: OBJETIVO: Este estudo examinou o uso de serviços de saúde por crianças, participação das mães na força de trabalho, e engajamento das mães na comunidade com base no risco da criança para atraso no desenvolvimento. MÉTODO: Usamos dados do estudo All Our Families, uma coorte prospectiva de gestantes. Os escores no Questionário Idades e Fases (QIF) na idade de 2 anos indicou risco de atraso no desenvolvimento. Para investigar o impacto do risco para atraso no desenvolviemnto quando crianças não tinham diagnóstico, uma análise de sensibilidade excluiu os relatos de desordem neurodesenvolvimental (DND) na idade de 3 anos. Os desfechos foram os relatos maternos sobre a saúde da criança e visitas a serviços de saúde (com custos estimados), e a participação das mães na força de trabalho e engajamento na comunidade nos anos 2 e 3. RESULTADOS: Entre 1314 díades mãe-criança, 209 (16%) crianças foram classificadas como tendo risco para atraso no desenvolvimento, e 42 (3%) tiveram diagnóstico de DND. O risco de atraso no desenvolvimento foi relacionado a um aumento no uso de serviços aliados de saúde (razão do risco de incidência 5,04 [ano 3]; intervalo de confiança a 95% 2,49-10,2) e consultas de saúde (razão do risco de incidência 1,33 [ano 3]; intervalo de confiança a 95% 1,14-1,54). A média esperada dos custos dos serviços aliados de saúde foi maior para crianças de risco versus aquelas sem risco para atraso no desenvolvimento. No entanto, quando excluídas da análise as crianças com diagnóstico reportado de DND, o maior uso dos serviços e custos no restante da população de risco não foram observados. O engajamento na comunidade e participação na força de trabalho entre famílias não diferiu com base no risco para atraso do desenvolvimento. INTERPRETAÇÃO: Os resultados sugerem que o uso aumentado de serviços de saúde por famílias com crianças com risco para atraso no desenvolvimento é causado por aqueles que receberam diagnóstico de DND no ano subsequente.

An Integrated Pipeline for Combining in vitro Data and Mathematical Models Using a Bayesian Parameter Inference Approach to Characterize Spatio-temporal Chemokine Gradient Formation.

All protective and pathogenic immune and inflammatory responses rely heavily on leukocyte migration and localization. Chemokines are secreted chemoattractants that orchestrate the positioning and migration of leukocytes through concentration gradients. The mechanisms underlying chemokine gradient establishment and control include physical as well as biological phenomena. Mathematical models offer the potential to both understand this complexity and suggest interventions to modulate immune function. Constructing models that have powerful predictive capability relies on experimental data to estimate model parameters accurately, but even with a reductionist approach most experiments include multiple cell types, competing interdependent processes and considerable uncertainty. Therefore, we propose the use of reduced modeling and experimental frameworks in complement, to minimize the number of parameters to be estimated. We present a Bayesian optimization framework that accounts for advection and diffusion of a chemokine surrogate and the chemokine CCL19, transport processes that are known to contribute to the establishment of spatio-temporal chemokine gradients. Three examples are provided that demonstrate the estimation of the governing parameters as well as the underlying uncertainty. This study demonstrates how a synergistic approach between experimental and computational modeling benefits from the Bayesian approach to provide a robust analysis of chemokine transport. It provides a building block for a larger research effort to gain holistic insight and generate novel and testable hypotheses in chemokine biology and leukocyte trafficking.

Stable cycling in quasi-linkage equilibrium: Fluctuating dynamics under gene conversion and selection.

Genetic systems with multiple loci can have complex dynamics. For example, mean fitness need not always increase and stable cycling is possible. Here, we study the dynamics of a genetic system inspired by the molecular biology of recognition-dependent double strand breaks and repair as it happens in recombination hotspots. The model shows slow-fast dynamics in which the system converges to the quasi-linkage equilibrium (QLE) manifold. On this manifold, sustained cycling is possible as the dynamics approach a heteroclinic cycle, in which allele frequencies alternate between near extinction and near fixation. We find a closed-form approximation for the QLE manifold and use it to simplify the model. For the simplified model, we can analytically calculate the stability of the heteroclinic cycle. In the discrete-time model the cycle is always stable; in a continuous-time approximation, the cycle is always unstable. This demonstrates that complex dynamics are possible under quasi-linkage equilibrium.

Stochastic transport in the presence of spatial disorder: Fluctuation-induced corrections to homogenization.

Motivated by uncertainty quantification in natural transport systems, we investigate an individual-based transport process involving particles undergoing a random walk along a line of point sinks whose strengths are themselves independent random variables. We assume particles are removed from the system via first-order kinetics. We analyze the system using a hierarchy of approaches when the sinks are sparsely distributed, including a stochastic homogenization approximation that yields explicit predictions for the extrinsic disorder in the stationary state due to sink strength fluctuations. The extrinsic noise induces long-range spatial correlations in the particle concentration, unlike fluctuations due to the intrinsic noise alone. Additionally, the mean concentration profile, averaged over both intrinsic and extrinsic noise, is elevated compared with the corresponding profile from a uniform sink distribution, showing that the classical homogenization approximation can be a biased estimator of the true mean.

N400 incongruity effect in an episodic memory task reveals different strategies for handling irrelevant contextual information for Japanese than European Canadians.

East Asians/Asian Americans show a greater N400 effect due to semantic incongruity between foreground objects and background contexts than European Americans (Goto, Ando, Huang, Yee, & Lewis, 2010). Using analytic attention instructions, we asked Japanese and European Canadians to judge, and later, remember, target animals that were paired with task-irrelevant original (congruent), or novel (incongruent) contexts. We asked: (1) whether the N400 also shows an episodic incongruity effect, due to retrieved contexts conflicting with later-shown novel contexts; and (2) whether the incongruity effect would be more related to performance for Japanese, who have been shown to have more difficulty ignoring such contextual information. Both groups exhibited episodic incongruity effects on the N400, with Japanese showing more typical N400 topographies. However, incongruent-trial accuracy was related to reduction of N400s only for the Japanese. Thus, we found that the N400 can reflect episodic incongruity which poses a greater challenge to Japanese than European Canadians.