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.

Normative values for grip strength, gait speed, timed up and go, single leg balance, and chair rise derived from the Canadian longitudinal study on ageing.

BACKGROUND: decreased muscle strength and physical function often precede disability, nursing home admission, home care use and mortality in older adults. Normative values for commonly used physical performance-based tests are not widely available for older adults but are required for clinicians and researchers to easily identify individuals with low performance. OBJECTIVE: to develop normative values for grip strength, gait speed, timed up and go, single-leg balance and five-repetition chair rise tests in a large population-based sample of Canadians aged 45-85 years. METHODS: baseline data (2011-2015) from the Canadian Longitudinal Study on Ageing was used to estimate age- and sex-specific normative values for each of the physical tests. Participants were without disability or mobility limitation (no assistance with activities of daily living or use of mobility devices). RESULTS: of the 25,470 participants eligible for the analyses 48.6% (n = 12,369) were female with a mean age of 58.6 ± 9.5 years. Sex-specific 5th, 10th, 20th, 50th, 80th, 90th and 95th percentile values for each physical performance-based test were estimated. Cross-validation (n = 100 repetitions) with a 30% holdout sample was used to evaluate model fit. CONCLUSIONS: the normative values developed in this paper can be used in clinical and research settings to identify individuals with low performance relative to their peers of the same age and sex. Interventions targeting these at-risk individuals including physical activity can prevent or delay mobility disability and the resulting cascade of increasing care requirements, health care costs and mortality.

Factors Influencing Mobility During the COVID-19 Pandemic in Community-Dwelling Older Adults.

OBJECTIVE: To describe and identify factors influencing mobility among older adults during the first 5 months of the COVID-19 pandemic. DESIGN: A cross-sectional telesurvey. SETTING: Community dwelling older adults, situated within the first 5 months of the COVID-19 pandemic, in Hamilton, Canada. PARTICIPANTS: A random sample of 2343 older adults were approached to be in the study, of which 247 completed the survey (N=247). Eligible participants were aged ≥65 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mobility was measured using global rating of change items and the Late Life Function Instrument (LLFI). Multivariate linear regression models were used to examine the association between mobility and related factors based on Webber's model. RESULTS: 247 older adults (29% male, mean age 78±7.3 years) completed surveys between May and August 2020. Respectively, 26%, 10%, and 9%, rated their ability to engage in physical activity, housework, and move around their home as worse compared with the start of the pandemic. The mean LLFI score was 60.9±13.4. In the model, walking volume (ß=0.03 95% confidence interval 0.013, 0.047), fall history (ß=-0.04, 95% confidence interval -0.08, -0.04), male sex (ß=0.06, 95% confidence interval 0.02, 0.09), unpleasant neighborhood (ß=-0.06, 95% confidence interval -0.11, -0.02), musculoskeletal pain (ß=-0.07, 95% confidence interval -0.11, -0.03), and self-reported health (ß=0.08, 95% confidence interval 0.03, 0.13) had the strongest associations with LLFI scores and explained 64% of the variance in the LLFI score. CONCLUSIONS: Physical and environmental factors may help explain poorer mobility during lockdowns. Future research should examine these associations longitudinally to see if factors remain consistent over time and could be targeted for rehabilitation.

Sex-stratified reference values for the life-space assessment in the Canadian longitudinal study on aging.

BACKGROUND: The Life-Space Assessment (LSA) can compliment traditional physical performance measures of mobility by accounting for the interaction between individuals and their environment. However, there are no studies that have generated percentile curves showing sex-stratified reference values in a large population-based sample of community-dwelling adults, making its interpretation difficult. Therefore, this study aimed to establish sex-stratified reference values for the LSA in middle-aged and older Canadians. METHODS: Baseline data for participants aged 45-84 years old from the Canadian Longitudinal Study on Aging (CLSA) were used (n = 22,154). Quantile regression was used to estimate specific percentiles, with age as the independent variable and LSA scores as the dependent variable. Models were run for the whole sample, then separately for males and females. The models were cross-validated to assess their reliability. CLSA inflation and analytic weights were applied. RESULTS: On average, the sample was 62.5 ± 10.0 y.o. (51.1% males), with a weighted mean LSA score of 89.2 ± 17.0. There was also a decrease in LSA scores with age, where scores were lower for older age groups compared to younger groups, and LSA scores were lower for females relative to males. DISCUSSION AND CONCLUSIONS: Reference data will aid in interpreting, comparing, and making inferences related to LSA scores obtained in clinical and research settings for Canadian adults.

Measuring physical performance in later life: reliability of protocol variations for common performance-based mobility tests.

BACKGROUND AND AIMS: Performance-based tests of mobility or physical function such as the Timed Up and Go (TUG), gait speed, chair-rise, and single-leg stance (SLS) are often administered using different protocols in aging populations, however, the reliability of their assessment protocols is not often considered. The purpose of this study was to examine the reliabilities of frequently used assessment protocols for the TUG, gait speed, chair-rise, and SLS in different age groups. METHODS: We administered the following assessment protocols in an age-stratified (50-64, 65-74, 75+ years) sample of participants (N = 147) from the Canadian Longitudinal Study on Aging (CLSA): TUG fast pace and TUG normal pace: TUG-cognitive counting backwards by ones and counting back by threes, gait speed with 3-m and 4-m course, chair-rise with arms crossed and allowing the use of arms, and SLS using preferred leg or both legs-on two occasions within 1 week. We assessed the relative (intra-class correlation) and absolute reliability (standard error of measurement, SEM and minimal detectable change, MDC) for each protocol variation and provided recommendations based on relative reliability. RESULTS: For participants aged 50-64 years, our results suggest better reliability for TUG fast-pace compared with normal-pace (ICC and 95% CI 0.70; 0.41-0.85 versus 0.38; 0.12-0.59). The reliability values for 3-m gait speed were potentially higher than for 4-m gait speed (ICC 0.75; 0.67-0.82 versus 0.64; 0.54-0.73) and values for chair-rise suggested better reliability allowing participants to use their arms than with arms crossed (ICC 0.79; 0.66-0.86 versus 0.64; 0.45-0.77) for participants overall. For participants aged 75+ years, ICCs for SLS with the preferred leg showed better reliability than for both legs (ICC = 0.62-0.79 versus 0.30-0.39). CONCLUSIONS AND DISCUSSION: These reliability data and the recommendations can help guide the selection of the most appropriate performance-based test protocols for measuring mobility in middle-aged and older community-dwelling adults.

Age-appropriate BMI cut-points for cardiometabolic health risk: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: Body composition changes that occur with aging pose unique health risks to older adults. The current World Health Organization (WHO) body mass index (BMI) cut-points may not accurately reflect health risks in older adults (65+). Prior findings suggest those classified as overweight may be conferred survival advantages. This study aims to define age-specific BMI cut-points for adults (45-64, 65-74, and 75-85 years) associated with cardiometabolic outcomes, and compare the performance of these thresholds to the WHO BMI thresholds using cardiometabolic conditions and frailty as outcomes. METHODS: Using baseline data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (N = 30,097), a classification and regression tree cross-sectional analysis was conducted to derive age-specific BMI cut-points based on cardiometabolic health risk. The area under the receiver operating curve (AUC), sensitivity, and specificity were estimated. Agreement with waist circumference was conducted. RESULTS: For older adults (65-74 and 75+ years old), the BMI threshold for identifying overweight increased to 26.9 and 26.6, respectively, from the WHO definition of 25.0 kg/m2. For obesity, the thresholds were revised to 29.0 and 30.9, respectively, from 30.0. The largest improvements to AUC occurred in older adults (65+). Across all age-sex stratifications, the new overweight threshold demonstrated lower sensitivity and higher specificity compared to the traditional threshold. Age-specific BMI thresholds demonstrated higher agreement with waist circumference for some age-sex stratifications and poor performance with hearing. CONCLUSIONS: Age-appropriate BMI thresholds for older adults may improve classification by health risk compared to standard WHO cut-points. A higher overweight threshold but lower obesity cut-points may be best suited to this demographic.

Mobility screening for fall prediction in the Canadian Longitudinal Study on Aging (CLSA): implications for fall prevention in the decade of healthy ageing.

BACKGROUND: Guidelines for fall prevention in older adults recommend mobility screening for fall risk assessment; however, there is no consensus on which test to use and at what cutoff. This study aimed to determine the accuracy and optimal cut-off values of commonly used mobility tests for predicting falls in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Mobility tests at baseline included the Timed Up and Go (TUG), Single Leg Stance (SLS), chair-rise and gait speed. Inclusion criteria were: age ≥ 65 years and meeting first-level fall screening criteria (i.e. history of a fall or mobility problem) at baseline. Accuracy of fall prediction at 18-months for each test was measured by the area under the receiver operating curve (AUC). RESULTS: Of 1,121 participants that met inclusion criteria (mean age 75.2 ± 5.9 years; 66.6% women), 218 (19.4%) reported ≥one fall at 18 months. None of the tests achieved acceptable accuracy for identifying individuals with ≥one fall at follow-up. Among women 65-74 and 75-85 years, the TUG identified recurrent fallers (≥two falls) with optimal cut-off scores of 14.1 and 12.9 s (both AUCs 0.70), respectively. Among men 65-74 years, only the SLS showed acceptable accuracy (AUC 0.85) for identifying recurrent fallers with an optimal cutoff of 3.6 s. CONCLUSIONS: Our findings indicate that commonly used mobility tests do not have sufficient discriminability to identify fallers in a population-based sample of community-dwelling older adults. The TUG and SLS can identify recurrent fallers; however, their accuracy and cut-off values vary by age and sex.

Body mass index, waist circumference, waist-to-hip ratio, and body fat in relation to health care use in the Canadian Longitudinal Study on Aging.

BACKGROUND/OBJECTIVES: Obesity is associated with increased health care use (HCU), but it is unclear whether this is consistent across all measures of adiposity. The objectives were to compare obesity defined by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and percent body fat (%BF), and to estimate their associations with HCU. SUBJECTS/METHODS: Baseline data from 30,092 participants aged 45-85 years from the Canadian Longitudinal Study on Aging were included. Measures of adiposity were recorded by trained staff and obesity was defined as BMI ≥ 30.0 kg/m2 for all participants and WC ≥ 88 cm and ≥102 cm, WHR ≥ 0.85 and ≥0.90, and %BF > 35% and >25% (measured using dual energy x-ray absorptiometry) for females and males, respectively. Self-reported HCU in the past 12 months was collected for any contact with a general practitioner, specialist, emergency department, and hospitalization. Pearson correlation coefficients (r) compared each measure to %BF-defined obesity, the reference standard. Relative risks (RR) and risk differences (RD) adjusted for age, sex, education, income, urban/rural, marital status, smoking status, and alcohol use were calculated, and results were age- and sex-stratified. RESULTS: Obesity prevalence varied by measure: BMI (29%), WC (42%), WHR (62%), and %BF (73%). BMI and WC were highly correlated with %BF (r ≥ 0.70), while WHR demonstrated a weaker relationship with %BF, with differences by sex (r = 0.29 and r = 0.46 in females and males, respectively). There were significantly increased RR and RD for all measures and health care services, for example, WC-defined obesity was associated with an increased risk of hospitalization (RR: 1.40, 95% CI: 1.28-1.54 and RD per 100: 2.6, 95% CI:1.9-3.3). Age-stratified results revealed that older adult groups with obesity demonstrated weak or no associations with HCU. CONCLUSIONS: All measures of adiposity were positively associated with increased HCU although obesity may not be a strong predictor of HCU in older adults.

The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).

The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.

Clustering of obesity-related characteristics: A latent class analysis from the Canadian Longitudinal Study on Aging.

Measures of obesity, including body mass index (BMI) and waist circumference (WC), do not fully capture the complexity of obesity-related health risks. This study identified distinct classes of obesity-related characteristics and evaluated their associations with BMI, WC, and percent body fat (%BF) using cross-sectional data from 30,096 participants aged 45-85 in the Canadian Longitudinal Study on Aging (2011-2015). Sixteen obesity-related variables, including behavioural, metabolic, physical health, and mental health/social factors, were included in a latent class analysis to identify distinct classes of participants. Adjusted odds ratios (OR) were estimated from logistic regression for associations between each class and obesity defined by BMI, WC and %BF. Six latent classes were identified: "low-risk" (39.8%), "cardiovascular risk" (19.4%), "metabolic risk" (16.9%), "sleep and mental health risk" (12.1%), "multiple and complex risk" (6.7%), and "cardiometabolic risk" (5.1%). Compared to "low-risk", all classes had increased odds of BMI-, WC- and %BF-defined obesity. For example, the "complex and multiple risk" class was associated with obesity by BMI (OR: 10.70, 95% confidence interval (CI): 9.51, 12.04), WC (OR: 9.21, 95% CI: 8,15, 10,41) and %BF (OR: 7.54, 95% CI: 6.21, 9.16). Distinct classes of obesity-related characteristics were identified and were strongly associated with obesity defined by multiple measures.

An Evolutionary Genetic Perspective of Eating Disorders.

Eating disorders (ED) including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) affect up to 5% of the population in Western countries. Risk factors for developing an ED include personality traits, family environment, gender, age, ethnicity, and culture. Despite being moderately to highly heritable with estimates ranging from 28 to 83%, no genetic risk factors have been conclusively identified. Our objective was to explore evolutionary theories of EDs to provide a new perspective on research into novel biological mechanisms and genetic causes of EDs. We developed a framework that explains the possible interactions between genetic risk and cultural influences in the development of ED. The framework includes three genetic predisposition categories (people with mainly AN restrictive gene variants, people with mainly BED variants, and people with gene variants predisposing to both diseases) and a binary variable of either the presence or absence of pressure to be thin. We propose novel theories to explain the overlapping characteristics of the subtypes of AN (binge/purge and restrictive), BN, and BED. For instance, mutations/structural gene variants in the same gene causing opposite effects or mutations in nearby genes resulting in partial disequilibrium for the genes causing AN (restrictive) and BED may explain the overlap of phenotypes seen in AN (binge/purge).

Assessing the Heritability of Complex Traits in Humans: Methodological Challenges and Opportunities.

The goal of this review article is to provide a conceptual based summary of how heritability estimates for complex traits such as obesity are determined and to explore the future directions of research in the heritability field. The target audience are researchers who use heritability data rather than those conducting heritability studies. The article provides an introduction to key concepts critical to understanding heritability studies including: i) definitions of heritability: broad sense versus narrow sense heritability; ii) how data for heritability studies are collected: twin, adoption, family and population-based studies; and iii) analytical techniques: path analysis, structural equations and mixed or regressive models of complex segregation analysis. For each section, a discussion of how the different definitions and methodologies influence heritability estimates is provided. The general limitations of heritability studies are discussed including the issue of "missing heritability" in which heritability estimates are significantly higher than the variance explained by known genetic variants. Potential causes of missing heritability include restriction of many genetic association studies to single nucleotide polymorphisms, gene by gene interactions, epigenetics, and gene by environment interactions. Innovative strategies of accounting for missing heritability including modeling techniques and improved software are discussed.

A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality.

Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0·81; 95 % CI 0·77, 0·85 for highest v. lowest quantile of intake, P het=0·04, I 2=43 %), CVD mortality (five studies; RR 0·73; 95 % CI 0·68, 0·78; P het=0·31, I 2=16 %), all CHD (three studies; RR 0·66; 95 % CI 0·48, 0·91; P het=0·0002, I 2=88 %) and CHD mortality (seven studies; RR 0·70; 95 % CI 0·64, 0·76; P het=0·65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0·71; 95 % CI 0·49, 1·03; P het=0·03, I 2=72 %) and stroke mortality (three studies; RR 0·83; 95 % CI 0·69, 1·00; P het=0·54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1·05; 95 % CI 0·69, 1·61; P het=0·04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death.

Nutrition labelling, marketing techniques, nutrition claims and health claims on chip and biscuit packages from sixteen countries.

OBJECTIVE: Food packages were objectively assessed to explore differences in nutrition labelling, selected promotional marketing techniques and health and nutrition claims between countries, in comparison to national regulations. DESIGN: Cross-sectional. SETTING: Chip and sweet biscuit packages were collected from sixteen countries at different levels of economic development in the EPOCH (Environmental Profile of a Community's Health) study between 2008 and 2010. SUBJECTS: Seven hundred and thirty-seven food packages were systematically evaluated for nutrition labelling, selected promotional marketing techniques relevant to nutrition and health, and health and nutrition claims. We compared pack labelling in countries with labelling regulations, with voluntary regulations and no regulations. RESULTS: Overall 86 % of the packages had nutrition labels, 30 % had health or nutrition claims and 87 % displayed selected marketing techniques. On average, each package displayed two marketing techniques and one health or nutrition claim. In countries with mandatory nutrition labelling a greater proportion of packages displayed nutrition labels, had more of the seven required nutrients present, more total nutrients listed and higher readability compared with those with voluntary or no regulations. Countries with no health or nutrition claim regulations had fewer claims per package compared with countries with regulations. CONCLUSIONS: Nutrition label regulations were associated with increased prevalence and quality of nutrition labels. Health and nutrition claim regulations were unexpectedly associated with increased use of claims, suggesting that current regulations may not have the desired effect of protecting consumers. Of concern, lack of regulation was associated with increased promotional marketing techniques directed at children and misleadingly promoting broad concepts of health.

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.].

A Call for Caution When Using Network Methods to Study Multimorbidity: An Illustration Using Data from the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: 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 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.

Sarcopenia Definition and Outcomes Consortium 2020 Definition: Association and Discriminatory Accuracy of Sarcopenia With Disability in the Canadian Longitudinal Study on Aging.

BACKGROUND: Previous sarcopenia definitions have poor discriminatory accuracy for identifying people with/without relevant health outcomes, and poor agreement between methods of operationalizing sarcopenia criterion. The 2020 Sarcopenia Definitions and Outcomes Consortium (SDOC) definition recommends grip strength (absolute, or standardized to body mass index, total body fat, lean arm mass, or weight), and gait speed. The agreement between methods of operationalizing grip strength and discriminatory accuracy of the SDOC definition for health outcomes such as activities of daily living (ADL) disability is unknown. METHODS: Cross-sectional analyses of 27 924 Canadian Longitudinal Study on Aging participants aged 45-85 at baseline (2012-2015) stratified by sex. The associations of the SDOC definitions with ADL disability were assessed using logistic regression. Area under the curve (AUC) analyses were conducted to assess discriminatory accuracy. Agreement between methods of operationalizing grip strength was measured using Cohen's kappa. RESULTS: Sarcopenia was associated with 1.60 (1.42-1.80) to 5.80 (4.89-6.88) greater odds of ADL disability with AUC values between 0.60 and 0.81. Agreement between methods of operationalizing grip strength was between 0.10-0.80 for grip strength alone and 0.45-0.91 when combined with gait speed. CONCLUSIONS: The SDOC-suggested criteria of grip strength and gait speed are significantly associated with ADL disability and have high discriminatory accuracy. However, the agreement between methods of operationalizing grip strength tended to be modest, and AUC, sensitivity, and specificity differed depending on the definition. We suggest a single measure of grip strength be considered and age-stratified cutoff values to improve AUC values.

Overprescription of antibiotics for treating hospitalized COVID-19 patients: A systematic review & meta-analysis.

Background: Empirical use of antibiotics was reported throughout the coronavirus disease of 2019 (COVID-19) pandemic; however, evidence of bacterial coinfection or secondary bacterial infection among COVID-19 patients was sparse. Antibiotic overprescription for COVID-19 patients without confirmed bacterial coinfection can increase antimicrobial resistance (AMR). The objective of this study is to assess the appropriateness of antibiotic use during COVID-19 by summarizing the frequency of antibiotic use among hospitalized COVID-19 and the frequency of antibiotic use in patients with COVID-19. Methods: A systematic search was conducted of the Embase, Medline, Web of Science, and Cochrane Library databases by generating search terms using the concepts of "COVID-19," "Bacterial Coinfection," "Secondary bacterial infection," and "Antimicrobial resistance" to identify studies reporting antibiotic prescription for hospitalized COVID-19 patients with or without bacterial coinfection. We excluded studies on outpatients, studies informed infection due to mechanical ventilation, and randomized controlled trials. The pooled estimate of the percentage of the total and confirmed appropriate antibiotic prescriptions provided to hospitalized COVID-19 patients was generated using a random effect meta-analysis with inverse variance weighting. The study protocol registration DOI is osf.io/d3fpm. Results: Of 157,623 participants from 29 studies (11 countries, 45 % women) included in our review, antibiotics were prescribed to 67 % of participants (CI 64 %-71 %, P < 0·001), of which 80 % (CI 76 %-83 %, P < 0·001) of prescriptions were for COVID-19 patients without confirmed bacterial coinfections. Antibiotic overprescription varied during different periods of the pandemic and between High-Income and Upper and Lower Middle-Income Countries. We found heterogeneity among the studies (I2 = 100 %). The risk of bias analysis showed that 100 % of the included studies had the proper sample framing, and we are at low risk of bias due to sampling. Discussion: We find greater than expected use of antibiotics to treat hospitalized COVID-19 patients without bacterial coinfections, which may contribute to AMR globally. Concrete guidelines for using antibiotics to treat COVID-19 patients, strict monitoring, and administering Antimicrobial Stewardship are needed to prevent overprescription.

Examining the immediate and ongoing impact of the COVID-19 pandemic on population-based estimates of dementia: a population-based time series analysis in Ontario, Canada.

OBJECTIVES: Population-based chronic disease surveillance systems were likely disrupted by the COVID-19 pandemic. The objective of this study was to examine the immediate and ongoing impact of the COVID-19 pandemic on the claims-based incidence of dementia. METHODS: We conducted a population-based time series analysis from January 2015 to December 2021 in Ontario, Canada. We calculated the monthly claims-based incidence of dementia using a validated case ascertainment algorithm drawing from routinely collected health administrative data. We used autoregressive linear models to compare the claims-based incidence of dementia during the COVID-19 period (2020-2021) to the expected incidence had the pandemic not occurred, controlling for seasonality and secular trends. We examined incidence by source of ascertainment and across strata of sex, age, community size and number of health conditions. RESULTS: The monthly claims-based incidence of dementia dropped from a 2019 average of 11.9 per 10 000 to 8.5 per 10 000 in April 2020 (32.6% lower than expected). The incidence returned to expected levels by late 2020. Across the COVID-19 period there were a cumulative 2990 (95% CI 2109 to 3704) fewer cases of dementia observed than expected, equivalent to 1.05 months of new cases. Despite the overall recovery, ascertainment rates continued to be lower than expected among individuals aged 65-74 years and in large urban areas. Ascertainment rates were higher than expected in hospital and among individuals with 11 or more health conditions. CONCLUSIONS: The claims-based incidence of dementia recovered to expected levels by late 2020, suggesting minimal long-term changes to population-based dementia surveillance. Continued monitoring of claims-based incidence is necessary to determine whether the lower than expected incidence among individuals aged 65-74 and in large urban areas, and higher than expected incidence among individuals with 11 or more health conditions, is transitory.