Explore the vast range of titles available.

Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets. Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.

Additionally, as first noted in a commentary published in 2001 in this journal, there continue to be conceptual and practical issues in determining the appropriate occurrence rates of living with multiple health issues [9]. [...]the objective of this commentary is to highlight the current issues in defining the broad concept of multimorbidity within the context of international research and to re-establish the distinction between the concepts of “multimorbidity” and “comorbidity.” [...]the accumulation is increasingly occurring in younger age groups, indicating a timely opportunity for prevention and a need to focus on patient-relevant outcome measures (PROMs). More appropriate uses of the term comorbidity exist in the literature and are framed as a focus on patients living with a specific chronic condition (such as diabetes, stroke, or dementia) and the implications of these conditions for complex management programs and clinical care delivery [27–29]. Because of the lack of clinical guidelines that actively account and respond to the challenges of multimorbidity in clinical management [15,30,31], the tools that are available to health care professionals often have a comorbidity orientation by assessing the impact of a co-occurring condition (or its management protocol) on another condition. [...]the authors acknowledge the complex interplay between comorbidity, multimorbidity, functional impairments, frailty, aging, patient-centeredness, and complexity.

Low lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV1), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population. From the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV1 with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV1 (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > -1 SD), 19% (n = 4,353) moderate (z-score -1 to > -2 SD), and 6% (n = 1,329) severely low FEV1 (z-score = < -2 SD). There was a graded association between lower FEV1 with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV1 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV1 with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred. We observed graded associations between lower FEV1 with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency.

ObjectiveTo describe the sociodemographic characteristics associated with e-cigarette ever use and to examine the impact of e-cigarette ever use on lung function impairment in an ageing population.DesignA cross-sectional analysis of data from the Canadian Longitudinal Study on Aging.SettingA national stratified sample of 44 817 adults living in Canadian provinces.ParticipantsRespondents included participants aged 45–85 and residing in the community in Canadian provinces.Outcome measuresThe Global Lung Function Initiative normative values for forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory ratio (FEV1/FVC) appropriate for age, sex, height and ethnicity were used to interpret the severity of lung function impairment. Multinomial logistic regression analysis was used to examine the impact of e-cigarette ever use on obstructive and restrictive lung function impairment.ResultsThe prevalence of e-cigarette ever use was 6.5% and varied by sociodemographic factors including higher prevalence among individuals younger than 65 years, those with lower education attainment and those with lower annual household income. E-cigarette ever use was associated with 2.10 (95% CI 1.57 to 2.08) times higher odds of obstructive lung function impairment after adjusting for conventional cigarette smoking and other covariates. Individuals with exposure to e-cigarette ever use and 15 or more pack-years had 7.43 (95% CI 5.30 to 10.38) times higher odds for obstructive lung function impairment when compared with non-smokers and non-e-cigarette users after adjusting for covariates. Smokers with 15 or more pack-years had higher odds of restrictive lung function impairment irrespective of e-cigarette ever use.ConclusionsEver use of e-cigarettes was found to be associated with obstructive lung function impairment after adjusting for covariates, suggesting that e-cigarette use may be adding to the respiratory and other chronic disease burden in the population.

COVID-19 infection can lead to multi-organ dysfunction, which has been shown to contribute to the physical disability seen in people after hospital discharge. We aimed to understand the effects of hospitalization for COVID-19 on mobility, cognition, and daily activities over 24-months of follow up. This was a 24-month extension of the COREG-FR prospective cohort study (NCT04602260). We enrolled consecutive adult patients (≥18 years) with lab confirmed SARS-Cov-2 infection who were admitted to five Ontario, Canada hospitals between August 21, 2020, and December 21, 2021. Patients were excluded if they resided in an institution (e.g., long term care facility), had severe premorbid physical function limitations (e.g., unable to stand independently) or had cognitive impairment which limited their ability to complete follow-up assessment. We assessed mobility and cognitive status using the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Domain and Cognitive Domain, respectively. Deficits from premorbid status were determined using the minimal clinically important differences in mobility (≥ 3.3) and cognition (≥ 5.5). We also asked participants how much their COVID-19 recovery affected their daily activities within the preceding week with response options from 'not at all' to 'all the time'. Among the 215 participants who participated 12-months after hospital discharge, 170 (79%) consented to the 24-month follow-up. The mean (standard deviation) age was 61.2 (12.7) years and 54% (n = 91) of participants who were male. Compared to pre-morbid function, mobility and cognitive deficits were present in 57% and 41% of participants, respectively. Furthermore, 59% of participants reported COVID-19 continued to impact their daily activities. At 24-months after hospitalization for COVID-19, many participants experience persistent mobility and cognitive deficits. Future work should aim to develop comprehensive rehabilitation strategies for those recovering from COVID-19 which target mobility and cognitive function.

Background Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments. Methods We searched MEDLINE ® , EMBASE ® , Cochrane Central Register of Controlled Trials ® , AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies. Results Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain). Conclusions The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems.

It is unknown if the relationship between multimorbidity and disability differs by combinations of chronic conditions. The objective of our study was to elucidate how joint effect of different combinations of chronic conditions impact the five year risk of functional disability at the population level. Participants ≥65 years from the Canadian Study of Health and Aging were assessed for functional disability measured using activities of daily living (ADL) and instrumental ADL (IADL), and the presence of conditions in five disease domains; cardiometabolic, neurological, sensory, musculoskeletal, and respiratory. Logistic regression was used to assess the relationship between each disease domain and incident ADL and IADL measured at five years of follow up and population attributable risk (PAR) was modeled for diseases domains that were significantly associated with disability. Results were stratified by sex and age (65-74 years, ≥75 years). There were 6272 participants free of ADL disability and 4571 participants free from IADL disability at baseline. For incident ADL, the greatest PAR values were 21.3 (9.8-32.8) for the cardiometabolic domain in males 65-74 years, 22.7 (4.7-40.8) for the musculoskeletal domain for females aged 65-74 years, and 11.2 (2.8-19.7) for the musculoskeletal domain in males ≥75 years. The PAR for the musculoskeletal, sensory, and neurological domains were similar in females ≥75 years(9.3-9.9). PAR values were lower but followed similar patterns for IADL disability. The chronic disease domains which most strongly predicted incident ADLs and IADLs did not account for the greatest amount of disability at the population level.

Background Monitoring and improving physical activity levels is essential for promoting healthy aging. The objective of this study was to create age-specific normative values for the Physical Activity Scale for the Elderly (PASE) among community-dwelling women and men aged 45–85 years old. Methods 36,701 participants (47% female) aged 45–85 years old, free of any mobility limitation or activities of daily living disability from the Canadian Longitudinal Study on Aging (CLSA) were included. Best fitting models were identified using Generalized Akaike Information Criteria values and cross-validation. Seasonal differences for males and females were also explored. Results Separate models for males and females are presented, providing a range of percentile values (5–95%) in charts and tables. Total PASE scores were highest in 45-year-olds and decreased with age. Seasonal differences were not substantial or consistent at the population level. Conclusions The age- and sex- specific normative values provided can improve the interpretability of PASE scores among middle-aged and older adults. In addition to PA guideline cut-offs, normative values provide further information for monitoring physical activity by allowing for more personalized observations that account for healthy variation.

Background Older adults have been disproportionately impacted by COVID-19 and related preventative measures undertaken during the pandemic. Given clear evidence of the relationship between loneliness and health outcomes, it is imperative to better understand if, and how, loneliness has changed for older adults during the COVID-19 pandemic, and whom it has impacted most. Method We used “pre-pandemic” data collected between 2015–2018 ( n  = 44,817) and “during pandemic” data collected between Sept 29-Dec 29, 2020 ( n  = 24,114) from community-living older adults participating in the Canadian Longitudinal Study on Aging. Loneliness was measured using the 3-item UCLA Loneliness Scale. Weighted generalized estimating equations estimated the prevalence of loneliness pre-pandemic and during the pandemic. Lagged logistic regression models examined individual-level factors associated with loneliness during the pandemic. Results We found the adjusted prevalence of loneliness increased to 50.5% (95% CI: 48.0%-53.1%) during the pandemic compared to 30.75% (95% CI: 28.72%-32.85%) pre-pandemic. Loneliness increased more for women (22.3% vs. 17.0%), those in urban areas (20.8% vs. 14.6%), and less for those 75 years and older (16.1% vs. 19.8% or more in all other age groups). Loneliness during the pandemic was strongly associated with pre-pandemic loneliness (aOR 4.87; 95% CI 4.49–5.28) and individual level sociodemographic factors [age < 55 vs. 75 + (aOR 1.41; CI 1.23–1.63), women (aOR 1.34; CI 1.25–1.43), and no post-secondary education vs. post-secondary education (aOR 0.73; CI 0.61–0.86)], living conditions [living alone (aOR 1.39; CI 1.27–1.52) and urban living (aOR 1.18; CI 1.07–1.30)], health status [depression (aOR 2.08; CI 1.88–2.30) and having two, or ≥ three chronic conditions (aOR 1.16; CI 1.03–1.31 and aOR 1.34; CI 1.20–1.50)], health behaviours [regular drinker vs. non-drinker (aOR 1.15; CI 1.04–1.28)], and pandemic-related factors [essential worker (aOR 0.77; CI 0.69–0.87), and spending less time alone than usual on weekdays (aOR 1.32; CI 1.19–1.46) and weekends (aOR 1.27; CI 1.14–1.41) compared to spending the same amount of time alone]. Conclusions As has been noted for various other outcomes, the pandemic did not impact all subgroups of the population in the same way with respect to loneliness. Our results suggest that public health measures aimed at reducing loneliness during a pandemic should incorporate multifactor interventions fostering positive health behaviours and consider targeting those at high risk for loneliness.