Discovery of hepatitis B virus subviral particle biogenesis inhibitors from a bioactive compound library.

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.

Impact of care-recipient relationship type on quality of life in caregivers of older adults with dementia over time.

BACKGROUND: Dementia caregiving is a dynamic and multidimensional process. To gain a comprehensive understanding of informal caregiving for people living with dementia (PLWD), it is pivotal to assess the quality of life (QoL) of informal caregivers. OBJECTIVE: To evaluate whether the care-recipient relationship type predicts changes in the QoL of informal caregivers of PLWD over a two-year period. METHODS: This was a secondary analysis of longitudinal data. The data were drawn from two waves of linked data from the National Health and Aging Trends Study (NHATS) and the National Study of Caregiving (NSOC) (2015: NHATS R5 & NSOC II; 2017: NHATS R7 & NSOC III). Caregivers were categorized into spousal, adult-child, "other" caregiver and "multiple" caregivers. QoL was assessed through negative emotional burden (NEB), positive emotional benefits and social strain (SS). Generalized estimating equation modelling was used to examine changes in caregivers' QoL outcomes across types of relationship over time. RESULTS: About, 882 caregivers were included who linked to 601 PLWD. After adjusting caregivers' socio-demographics, "other" caregivers had lower risk of NEB and SS than spousal caregivers (OR = 0.34, P = 0.003, 95%CI [0.17, 0.70]; OR = 0.37, P = 0.019, 95%CI 0.16, 0.85], respectively), and PLWD's dementia status would not change these significance (OR = 0.33, P = 0.003, 95%CI [0.16, 0.68]; OR = 0.31, P = 0.005, 95%CI [0.14, 0.71], respectively). CONCLUSIONS: The study demonstrates that spousal caregivers face a higher risk of NEB and SS over time, underscoring the pressing need to offer accessible and effective support for informal caregivers of PLWD, especially those caring for their spouses.

A call for caution when using network methods to study multimorbidity: an illustration using data from the Canadian Longitudinal Study on Aging.

OBJECTIVES: To examine the impact of two key choices when conducting a network analysis (clustering methods and measure of association) on the number and type of multimorbidity clusters. STUDY DESIGN AND SETTING: Using cross-sectional self-reported data on 24 diseases from 30,097 community-living adults aged 45-85 from the Canadian Longitudinal Study on Aging, we conducted network analyses using 5 clustering methods and 11 association measures commonly used in multimorbidity studies. We compared the similarity among clusters using the adjusted Rand index (ARI); an ARI of 0 is equivalent to the diseases being randomly assigned to clusters, and 1 indicates perfect agreement. We compared the network analysis results to disease clusters independently identified by two clinicians. RESULTS: Results differed greatly across combinations of association measures and cluster algorithms. The number of clusters identified ranged from 1 to 24, with a low similarity of conditions within clusters. Compared to clinician-derived clusters, ARIs ranged from -0.02 to 0.24, indicating little similarity. CONCLUSION: These analyses demonstrate the need for a systematic evaluation of the performance of network analysis methods on binary clustered data like diseases. Moreover, in individual older adults, diseases may not cluster predictably, highlighting the need for a personalized approach to their care.

Patient factors associated with cancer worry post-breast reconstruction: A cross-sectional study.

PURPOSE: The BREAST-Q Breast Cancer module is a patient-reported outcome measure for women with breast cancer diagnosis. Our research team developed and validated a novel BREAST-Q scale for this module that measures quality of life outcomes specific to cancer worry. The aim of this study was to investigate patient related breast reconstruction factors that are associated with worse scores on the new BREAST-Q Cancer Worry Scale. METHODS: Women with a history of breast cancer treated with mastectomy and reconstruction, aged ≥18 years, and English-speaking were recruited through the Love Research Army between October and November 2019. Participants completed demographic and clinical questions alongside the BREAST-Q Cancer Worry Scale. Univariable and multivariable regression analyses were used to identify participant characteristics associated with cancer worry scores. RESULTS: Among the 554 potential respondents, 538 (97.1%) completed the Cancer Worry Scale. The average patient age was 58.4 (+9.8) years. Cancer Worry scores were normally distributed with a mean of 46.4 (+17.2). Cancer Worry scores were significantly associated (p < 0.01) with younger age, history of radiation therapy, complications associated with breast surgery since diagnosis, use of textured breast implants, and shorter duration since surgery. CONCLUSIONS: This exploratory analysis provides evidence of patient characteristics that may be associated with cancer worry following postmastectomy breast reconstruction.

Correction: Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

[This corrects the article DOI: 10.1371/journal.pone.0292788.].

Effect of Age-Friendly Communities Action Plan on Trajectories of Older Canadians' Depressive Symptoms Between 2018 and 2020: Multilevel Results From the Canadian Longitudinal Study on Aging.

As the COVID-19 pandemic impacted mental health, this longitudinal study examined the effect of age-friendly communities (AFC) action plan on older adults' depressive symptoms. Using the CLSA, the CLSA COVID-19 Questionnaire study, survey of Canadian municipalities, and the census, the depressive symptoms trajectories were modeled with multilevel multinomial regressions. Most respondents (66.1%) had non-depressed trajectories, 28.1% experienced a moderate increase in depressive symptoms, and 5.8% had a depressed trajectory. AFC action plans did not have a protective effect on these trajectories. Being a female, greater loneliness, lower income, ≥2 chronic conditions, inferior social participation, weaker sense of belonging, COVID-19 infection, and pandemic stressors predicted a depressed trajectory. Neighborhood's deprivation had a weak protective effect on the declining trajectory. Although AFC action plans provided no benefits during the pandemic, volunteers facilitating resource access and social interactions could limit any increase in depressive symptoms.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Drug and Natural Health Product Data Collection and Curation in the Canadian Longitudinal Study on Aging.

This study aimed to develop an efficient data collection and curation process for all drugs and natural health products (NHPs) used by participants to the Canadian Longitudinal Study on Aging (CLSA). The three-step sequential process consisted of (a) mapping drug inputs collected through the CLSA to the Health Canada Drug Product Database (DPD), (b) algorithm recoding of unmapped drug and NHP inputs, and (c) manual recoding of unmapped drug and NHP inputs. Among the 30,097 CLSA comprehensive cohort participants, 26,000 (86.4%) were using a drug or an NHP with a mean of 5.3 (SD 3.8) inputs per participant user for a total of 137,366 inputs. Of those inputs, 70,177 (51.1%) were mapped to the Health Canada DPD, 20,729 (15.1%) were recoded by algorithms, and 44,108 (32.1%) were manually recoded. The Direct algorithm correctly classified 99.4 per cent of drug inputs and 99.5 per cent of NHP inputs. We developed an efficient three-step process for drug and NHP data collection and curation for use in a longitudinal cohort.

Validating the Emergency Department Avoidability Classification (EDAC): A cluster randomized single-blinded agreement study.

INTRODUCTION: The Emergency Department Avoidability Classification (EDAC) retrospectively classifies emergency department (ED) visits that could have been safely managed in subacute primary care settings, but has not been validated against a criterion standard. A validated EDAC could enable accurate and reliable quantification of avoidable ED visits. We compared agreement between the EDAC and ED physician judgements to specify avoidable ED visits. MATERIALS AND METHODS: We conducted a cluster randomized, single-blinded agreement study in an academic hospital in Hamilton, Canada. ED visits between January 1, 2019, and December 31, 2019 were clustered based on EDAC classes and randomly sampled evenly. A total of 160 ED visit charts were randomly assigned to ten participating ED physicians at the academic hospital for evaluation. Physicians judged if the ED visit could have been managed appropriately in subacute primary care (an avoidable visit); each ED visit was evaluated by two physicians independently. We measured interrater agreement between physicians with a Cohen's kappa and 95% confidence intervals (CI). We evaluated the correlation between the EDAC and physician judgements using a Spearman rank correlation and ordinal logistic regression with odds ratios (ORs) and 95% CIs. We examined the EDAC's precision to identify avoidable ED visits using accuracy, sensitivity and specificity. RESULTS: ED physicians agreed on 139 visits (86.9%) with a kappa of 0.69 (95% CI 0.59-0.79), indicating substantial agreement. Physicians judged 96.2% of ED visits classified as avoidable by the EDAC as suitable for management in subacute primary care. We found a high correlation between the EDAC and physician judgements (0.64), as well as a very strong association to classify avoidable ED visits (OR 80.0, 95% CI 17.1-374.9). The EDACs avoidable and potentially avoidable classes demonstrated strong accuracy to identify ED visits suitable for management in subacute care (82.8%, 95% CI 78.2-86.8). DISCUSSION: The EDAC demonstrated strong evidence of criterion validity to classify avoidable ED visits. This classification has important potential for accurately monitoring trends in avoidable ED utilization, measuring proportions of ED volume attributed to avoidable visits and informing interventions intended at reducing ED use by patients who do not require emergency or life-saving healthcare.

Lifetime Physical Activity and Late-Life Mild Cognitive Impairment in Community-Dwelling Older Adults.

OBJECTIVES: Regular physical activity throughout life is generally recommended to prevent dementia; however, there is little evidence regarding the association between lifetime physical activity and mild cognitive impairment (MCI), which often precedes dementia. This study aimed to examine the association of lifetime physical activity and their transitions with late-life MCI. DESIGN: A population-based case-control study. SETTING AND PARTICIPANTS: A total of 2968 Japanese community-dwelling older adults aged ≥70 years without dementia. METHODS: We evaluated the participants' early-, mid-, and late-life physical activity habits and categorized their transitions across life stages. Cognitive functions in late life were assessed for memory, attention, executive function, and processing speed; functional impairment in one or more cognitive domains was defined as MCI. RESULTS: Regular physical activity in early life was not significantly associated with late-life MCI [odds ratio (OR), 0.80; 95% CI, 0.63-1.02], although those in mid-life (OR, 0.64; 95% CI, 0.51-0.81) and late-life (OR, 0.74; 95% CI, 0.59-0.91) were associated with lower odds of late-life MCI. Compared with nonexercisers, participants who acquired new habits of physical activity during mid- or late-life (OR, 0.71; 95% CI, 0.55-0.91) and those who maintained physical activity throughout their life span (OR, 0.61; 95% CI, 0.42-0.87) had lower odds of late-life MCI; those who stopped regular activity during mid- or late-life did not (OR, 0.79; 95% CI, 0.58-1.06). CONCLUSIONS AND IMPLICATIONS: While physical activity throughout the life span is associated with the lowest odds of MCI, starting regular physical activity, even later in life, confers a benefit and should be encouraged as a "lifelong approach" to MCI risk reduction.

Associations between Osteosarcopenia and Falls, Fractures, and Frailty in Older Adults: Results From the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To explore if older adults with osteosarcopenia are at a greater risk of falls, fractures, frailty, and worsening life satisfaction and activities of daily living (ADL) compared to those with normal bone mineral density (BMD) and without sarcopenia. DESIGN: The baseline and 3-year follow-up of a longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling people aged 65 years or older in Canada. METHODS: Caucasian participants 65 years or older that completed the Canadian Longitudinal Study on Aging (CLSA) 2015 baseline interview, physical measurements and 3-year follow-up were included. Osteopenia/osteoporosis was defined as BMD T score below -1 SD according to the World Health Organization, and sarcopenia was defined as low grip strength and/or low gait speed according to the Sarcopenia Definition Outcomes Consortium. Osteosarcopenia was defined as the coexistence of osteopenia/osteoporosis and sarcopenia. Self-reported incident falls and fractures in the last 12 months before the 3-year follow-up were measured. Frailty was assessed through the Rockwood Frailty Index (FI); life satisfaction through the Satisfaction With Life Scale (SWLS); and ADL through the Older American Resources and Services modules. Multivariable logistic and linear regression, including subgroup analyses by sex, were conducted. RESULTS: The sample of 8888 participants (49.1% females) had a mean age (SD) of 72.7 (5.6) years. At baseline, neither osteopenia/osteoporosis nor sarcopenia (reference group) was present in 30.1%, sarcopenia only in 18.4%, osteopenia/osteoporosis only in 29.2%, and osteosarcopenia in 22.3%. Osteosarcopenia was significantly associated with incident falls and fractures in males [adjusted odds ratio (aOR), 1.90, 95% CI 1.15, 3.14, and aOR 2.60, 95% CI 1.14, 5.91, respectively] compared to males without osteopenia/osteoporosis or sarcopenia. Participants with osteosarcopenia had worsening ADL of 0.110 (estimated ß coefficient 0.110, 95% CI 0.029, 0.192) and a decrease in their SWLS by 0.660 (estimated ß coefficient -0.660, 95% CI -1.133, -0.187), compared to those without. Osteosarcopenia was not associated with frailty for both males and females. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia was associated with self-reported incident falls and fractures in males and worse life satisfaction and ADL for all participants. Assessing and identifying osteosarcopenia is essential for preventing falls and fractures. Furthermore, it improves life satisfaction and ADL.

Does urban greenness reduce loneliness and social isolation among Canadians? A cross-sectional study of middle-aged and older adults of the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVES: Urban greenness has been shown to confer many health benefits including reduced risks of chronic disease, depression, anxiety, and, in a limited number of studies, loneliness. In this first Canadian study on this topic, we investigated associations between residential surrounding greenness and loneliness and social isolation among older adults. METHODS: This cross-sectional analysis of the Canadian Longitudinal Study on Aging included 26,811 urban participants between 45 and 86 years of age. The Normalized Difference Vegetation Index (NDVI), a measure of greenness, was assigned to participants' residential addresses using a buffer distance of 500 m. We evaluated associations between the NDVI and (i) self-reported loneliness using the Center for Epidemiological Studies Depression Scale, (ii) whether participants reported "feeling lonely living in the local area", and (iii) social isolation. Logistic regression models were used to characterize associations between greenness and loneliness/social isolation while adjusting for individual socio-economic and health behaviours. RESULTS: Overall, 10.8% of participants perceived being lonely, while 6.5% reported "feeling lonely in their local area". Furthermore, 16.2% of participants were characterized as being socially isolated. In adjusted models, we observed no statistically significant difference (odds ratio (OR) = 0.99; 95% confidence interval (CI) 0.93-1.04) in self-reported loneliness in relation to an interquartile range (IQR) increase of NDVI (0.06). However, for the same change in greenness, there was a 15% (OR = 0.85; 95% CI 0.72-0.99) reduced risk for participants who strongly agreed with "feeling lonely living in the local area". For social isolation, for an IQR increase in the NDVI, we observed a 7% (OR = 0.93; 95% CI 0.88-0.97) reduction in prevalence. CONCLUSION: Our findings suggest that urban greenness plays a role in reducing loneliness and social isolation among Canadian urbanites.

RéSUMé: OBJECTIFS: Il est démontré que la verdure urbaine confère de nombreux avantages pour la santé; elle réduit notamment les risques de maladies chroniques, de dépression et d'anxiété et, selon un petit nombre d'études, le risque de solitude. Dans cette première étude canadienne sur le sujet, nous avons étudié les associations entre la verdure de l'environnement résidentiel et la solitude et l'isolement social chez les adultes d'âge mûr. MéTHODE: Cette analyse transversale de l'Étude longitudinale canadienne sur le vieillissement a inclus 26 811 participantes et participants urbains de 45 à 86 ans. L'indice de végétation par différence normalisée (IVDN), un indicateur de verdure, a été assigné à l'adresse domiciliaire dans une zone tampon de 500 m. Nous avons évalué les associations entre l'IVDN et i) la solitude autodéclarée selon l'échelle de dépression du Center for Epidemiological Studies, ii) le fait de déclarer « vivre de la solitude dans sa zone locale ¼ et iii) l'isolement social. Des modèles de régression logistique ont servi à caractériser les associations entre la verdure et la solitude/l'isolement social, et nous avons apporté des ajustements pour tenir compte du statut socioéconomique et des comportements de santé individuels. RéSULTATS: Globalement, 10,8 % des participantes et des participants se sentaient seuls, et 6,5 % disaient « vivre de la solitude dans leur zone locale ¼. De plus, 16,2 % des participantes et des participants ont été caractérisés comme étant socialement isolés. Dans nos modèles ajustés, nous n'avons observé aucun écart significatif (rapport de cotes (RC) = 0,99; IC de 95 % : 0,93­1,04) dans la solitude autodéclarée en lien avec une augmentation de l'écart interquartile (EI) de l'IVDN (0,06). Cependant, pour le même changement dans la verdure, la probabilité pour les participantes et les participants d'être tout à fait d'accord avec l'énoncé qu'ils « vivent de la solitude dans leur zone locale ¼ était réduite de 15 % (RC = 0,85, IC de 95 % : 0,72­0,99). Et pour chaque augmentation de l'EI de l'IVDN, nous avons observé une baisse de 7 % (RC = 0,93, IC de 95 % : 0,88­0,97) de la prévalence de l'isolement social. CONCLUSION: Nos constatations indiquent que la verdure urbaine joue un rôle dans la réduction de la solitude et de l'isolement social chez les citadins et citadines au Canada.

Physical frailty and survival time after the onset of functional disability: Is there a sex difference?

BACKGROUND: Physical frailty accelerates the timing of both subsequent disability and death; however, evidence regarding the impact of frailty on the period from disability onset to death and sex differences of this impact is lacking. The aim of this study was to examine the relationship among physical frailty, disability, death, and sex differences. METHODS: This Japanese cohort study included 10,524 community-dwelling people aged ≥65 years. Physical frailty was operationalized by key phenotypes as per Fried's criteria (slowness, weakness, exhaustion, weight loss, and low activity) at baseline. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for disability onset and post-disability survival according to the frailty status. RESULTS: During a 5-year follow-up, the risk of disability onset for pre-frailty (HR: 1.74, 95% CI: 1.51-2.00) and frailty (HR: 3.27, 95% CI: 2.77-3.87) were significantly higher than that for robust people. Furthermore, among participants who developed disabilities within 5 years (n = 1481), the risk of post-disability death for pre-frailty was not different from that for robust (HR: 1.49, 95% CI: 0.99-2.24), but frailty showed a higher risk of post-disability death than did robust people. (HR: 1.75, 95% CI: 1.13-2.72). In the sex-stratified analysis, although the female group showed no association between frailty status and post-disability death (HR: 1.21, 95% CI: 0.63-2.33 in pre-frailty; HR: 1.24, 95% CI: 0.60-2.57 in frailty), the male group showed higher risk of post-disability death in both pre-frailty (HR: 1.74, 95% CI: 1.03-2.96) and frailty (HR: 2.32, 95% CI: 1.32-4.09). CONCLUSIONS: Physical frailty shortens the period from disability onset to death. Additionally, the impact of frailty on post-disability death is greater for males than for females. Our findings suggest that physical frailty is an important clinical indicator distinct from disability and that interventions to prevent and address frailty in men need further investigation.

The Effects of Cognitive Ability, Mental Health, and Self-Quarantining on Functional Ability of Older Adults During the COVID-19 Pandemic: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVES: Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. DESIGN AND SETTING: Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). PARTICIPANTS: 17 541 CLSA participants. MEASUREMENTS: Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. RESULTS: Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). CONCLUSIONS: Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.

Impact of Care-Recipient Relationship Type on Quality of Life in Community-Dwelling Older Adults With Dementia Over Time.

INTRODUCTION: Maintaining quality of life (QoL) has been identified as the primary goal of care services for person living with dementia (PLWD). METHODS: A secondary analysis was conducted on five rounds of the National Health and Aging Trends Study (NHATS) over 4 years. A generalized estimating equation (GEE) was used to examine the prediction of relationship type on older adults' QoL through four domains: mental health, general health, functional limitations, and pain. RESULTS: older adults cared for by an adult-child or multiple caregivers predicted increased risk for functional limitations after adjustment for their socio-demographic and dementia status (IRR = 1.53, CI [1.26, 1.86]; IRR = 1.36, CI [1.14, 1.61], respectively). The interaction between the relationship type and education was significant. Older adults with a high school education or below, who were cared for by an adult child, had a significantly higher risk of increasing functional limitations over 4 years compared to those cared for by a spouse/partner (contrast = .50, P = .01, 95% CI [.07, .93]; contrast=.52, P = .03, 95% CI [.03, 1.02]; respectively). Similarly, older adults with a high school education, who were cared for by multiple caregivers, also experienced a significantly higher risk of increasing functional limitations than those cared for by a spouse/partner (contrast = .44, P = .03, 95% CI [.02, .85]). CONCLUSION: Our findings provide evidence of the significant contribution of relationship type on PLWD's QoL changes over time. They also help to prioritize resource allocation while addressing PLWD's demands by socio-demographics such as education level.

Protocol for validating an algorithm to identify neurocognitive disorders in Canadian Longitudinal Study on Aging participants: an observational study.

INTRODUCTION: In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data. METHODS AND ANALYSIS: Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated. ETHICS AND DISSEMINATION: Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.

Public Health Surveillance of Behavioral Cancer Risk Factors During the COVID-19 Pandemic: Sentiment and Emotion Analysis of Twitter Data.

BACKGROUND: The COVID-19 pandemic and its associated public health mitigation strategies have dramatically changed patterns of daily life activities worldwide, resulting in unintentional consequences on behavioral risk factors, including smoking, alcohol consumption, poor nutrition, and physical inactivity. The infodemic of social media data may provide novel opportunities for evaluating changes related to behavioral risk factors during the pandemic. OBJECTIVE: We explored the feasibility of conducting a sentiment and emotion analysis using Twitter data to evaluate behavioral cancer risk factors (physical inactivity, poor nutrition, alcohol consumption, and smoking) over time during the first year of the COVID-19 pandemic. METHODS: Tweets during 2020 relating to the COVID-19 pandemic and the 4 cancer risk factors were extracted from the George Washington University Libraries Dataverse. Tweets were defined and filtered using keywords to create 4 data sets. We trained and tested a machine learning classifier using a prelabeled Twitter data set. This was applied to determine the sentiment (positive, negative, or neutral) of each tweet. A natural language processing package was used to identify the emotions (anger, anticipation, disgust, fear, joy, sadness, surprise, and trust) based on the words contained in the tweets. Sentiments and emotions for each of the risk factors were evaluated over time and analyzed to identify keywords that emerged. RESULTS: The sentiment analysis revealed that 56.69% (51,479/90,813) of the tweets about physical activity were positive, 16.4% (14,893/90,813) were negative, and 26.91% (24,441/90,813) were neutral. Similar patterns were observed for nutrition, where 55.44% (27,939/50,396), 15.78% (7950/50,396), and 28.79% (14,507/50,396) of the tweets were positive, negative, and neutral, respectively. For alcohol, the proportions of positive, negative, and neutral tweets were 46.85% (34,897/74,484), 22.9% (17,056/74,484), and 30.25% (22,531/74,484), respectively, and for smoking, they were 41.2% (11,628/28,220), 24.23% (6839/28,220), and 34.56% (9753/28,220), respectively. The sentiments were relatively stable over time. The emotion analysis suggests that the most common emotion expressed across physical activity and nutrition tweets was trust (69,495/320,741, 21.67% and 42,324/176,564, 23.97%, respectively); for alcohol, it was joy (49,147/273,128, 17.99%); and for smoking, it was fear (23,066/110,256, 20.92%). The emotions expressed remained relatively constant over the observed period. An analysis of the most frequent words tweeted revealed further insights into common themes expressed in relation to some of the risk factors and possible sources of bias. CONCLUSIONS: This analysis provided insight into behavioral cancer risk factors as expressed on Twitter during the first year of the COVID-19 pandemic. It was feasible to extract tweets relating to all 4 risk factors, and most tweets had a positive sentiment with varied emotions across the different data sets. Although these results can play a role in promoting public health, a deeper dive via qualitative analysis can be conducted to provide a contextual examination of each tweet.

An Exploration of Methods to Resolve Inconsistent Self-Reporting of Chronic Conditions and Impact on Multimorbidity in the Canadian Longitudinal Study on Aging.

OBJECTIVES: To quantify inconsistent self-reporting of chronic conditions between the baseline (2011-2015) and first follow-up surveys (2015-2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity. METHODS: Community-dwelling adults aged 45-85 years in the baseline and first follow-up surveys were included (n = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions. Identifiable inconsistent responses were enumerated. RESULTS: 32-40% of participants had at least one inconsistent response across all conditions. Illness-related information (e.g., taking medication) resolved most inconsistent responses (>93%) while computer-assisted software asking participants to confirm their inconsistent disease status resolved ≤53%. Using these adjudication methods, multimorbidity prevalence at follow-up increased by ≤1.6% compared to the prevalence without resolving inconsistent responses. DISCUSSION: Inconsistent self-reporting of chronic conditions is common but may not substantially affect multimorbidity prevalence. Future research should validate methods to resolve inconsistencies.

Pre-Clinical Mobility Limitation (PCML) Outcomes in Rehabilitation Interventions for Middle-Aged and Older Adults: A Scoping Review.

Individuals with pre-clinical mobility limitation (PCML) are at a high risk of future functional loss and progression to disability. The purpose of this scoping review was to provide a comprehensive understanding of PCML intervention studies in middle-aged and older adults. We present the interventions that have been tested or planned, describe how they have been conducted and reported, identify the knowledge gaps in current literature, and make recommendations about future research directions. An initial search of 2,291 articles resulted in 14 articles that met criteria for inclusion. Findings reveal that: (1) there is limited published work on PCML interventions, especially in middle-aged populations; and (2) the complexity and variety of PCML measures make it difficult to compare findings across PCML studies. Despite the diversity of measures, this review provides preliminary evidence that rehabilitation interventions on PCML help to delay or prevent disability progression.