BACKGROUND:A 12-month trial economic evaluation was conducted to compare the Triple P-Positive Parenting Program (Triple P) versus treatment as usual (TAU) and the Circle of Security Parenting Program (COSP) versus TAU from a societal perspective. METHODS:Trial data were used to determine the costs of delivering the interventions and the 12-month costs associated with children's health and social care service use based on the Child and Adolescent Service Use Schedule questionnaire, which was completed by caregivers of children aged 2-6. All costs were expressed in 2024 Canadian dollars. To calculate quality-adjusted-life-years (QALYs), caregivers documented their children's quality of life using the Health Status Classification System Preschool Version (HSCSPV) and the Health Utility Index 3 for children less or more than 5 years of age, respectively. Cost-effectiveness acceptability curves were used to represent the uncertainty. Several sensitivity analyses were conducted (e.g., change in Triple P intervention costs). RESULTS:The trial recruited 502 caregivers (93% female, mean age [standard deviation] of 36 years [6.7]) of 502 children (41% female, mean age of 3.8 years [SD = 1.4]). The differences in 12-month societal costs and QALYs between Triple P and TAU were $121 (95% Confidence interval [CI]: -$258, $486) and 0.009 (95% CI: -0.018, 0.039), respectively. The differences in 12-month societal costs and QALYs between COSP and TAU were -$253 (95% CI: -$552, $40) and 0.004 (95% CI: -0.026, 0.035), respectively. Assuming that society was willing to spend up to $100,000 for each additional QALY gained, the probabilities that Triple P and COSP were cost-effective compared to TAU were 0.71 and 0.68, respectively. The results of the sensitivity analyses were consistent with the main analyses. CONCLUSIONS:The trial results suggest that compared to TAU, Triple P and COSP represent efficient use of public resources.

Frailty is a modifiable aging-related condition driven by chronic inflammation and metabolic dysregulation, which are influenced by diet. Metabolomic profiling captures individual metabolic responses and can uncover mechanisms linking diet to frailty. This study examined the effects of food-derived metabolites on changes in frailty risk, both directly and through inflammatory pathways. This longitudinal study included baseline and three-year follow-up data from 9992 participants aged 45-85 years from the Canadian Longitudinal Study on Aging with plasma metabolomic profiling. Inflammation was assessed using tumor necrosis factor alpha, interleukin-6, and C-reactive protein. Frailty was operationalized using Fried’s frailty phenotype and the deficit accumulation model. Metabolomic clusters reflecting shared dietary sources and/or biological function were associated with frailty risk, mediated by inflammation. Plasmalogens and furan fatty acids from protein-based foods, and those with anti-inflammatory properties from fruits, vegetables, nuts and legumes, were associated with reduced frailty risk both directly and indirectly through lower inflammation. Conversely, higher omega-6 to omega-3 ratio from fish/eggs and trans-4-hydroxyproline from processed meat increased frailty risk through pro-inflammatory mechanisms. These findings emphasize inflammation as an important mechanism linking diet to frailty and highlight the importance of nutrient balance and interactions to inform nutrition strategies and promote healthy aging.

Background Shift work is known to be a risk factor for metabolic diseases. Although not established within literature, socioeconomic disadvantage may be associated with increased risk of being engaged in these shift work patterns.Aim To examine whether socioeconomic factors are associated with the likelihood of engaging in shift work.Methods Using data from the Canadian Longitudinal Study on Aging (CLSA), we conducted a cross-sectional analysis of adults aged 45-85 years. We created a Social Disadvantage Score composed of points derived from immigration status, language, education and race, ranging from 0 to 6. Logistic regression models were used to examine the association between social disadvantage and shift work, while adjusting for relevant covariates. We performed similar analyses using data from the Hoorn Study in the Netherlands-focused on the association between educational attainment and shift work.Results Of 18,393 adults employed in the CLSA at baseline, 16.6% reported currently working in a shift work scheduled job. Odds of shift work employment increased progressively with Social Disadvantage Score. Individuals with the highest scores (4+) had 3.25 times the odds (95% CI: 2.24-4.72) of being employed in shift work compared to those with a score of 0. Of 709 adults in the Hoorn Study, 11.4% worked in shift work patterns. Lower education was associated with shift work employment (OR 1.74, 95% CI: 1.1-2.9).Conclusions Social disadvantage is strongly associated with shift work in Canada, and in the Netherlands, lower education is associated with shift work.

AIMS:Circadian regulation of metabolism is an important factor in metabolic health, yet the role of rhythmic metabolites in Type 2 diabetes development remains poorly understood. This study investigated associations between circulating rhythmic metabolites and incident Type 2 diabetes risk and evaluated causal relationships using two-sample Mendelian randomisation. MATERIALS AND METHODS:We analysed longitudinal data from 9992 community-dwelling adults aged 45-85 years (49.1% male) in the Canadian Longitudinal Study on Aging with baseline (2012-2015) serum metabolomics data. Untargeted metabolomics profiling was conducted using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Incident Type 2 diabetes at 3-year follow-up was assessed based on diabetes medication use and HbA1c level. Associations between rhythmic metabolites and diabetes risk were evaluated using multivariable binomial regression. Pathway and network analyses were conducted to explore underlying biological mechanisms. Causality was assessed using two-sample Mendelian randomisation for rhythmic metabolites significantly associated with diabetes risk. RESULTS:Altogether, 20 rhythmic metabolites were associated with Type 2 diabetes risk, including a subset overlapping with genetic predisposition to chronotype, suggesting potential circadian regulation. Key pathways included leucine, isoleucine and valine biosynthesis and degradation, and glycine, serine and threonine metabolism. Mendelian randomisation analyses revealed causal associations between higher levels of mannose, valine, isoleucine, threonine and sphingomyelin (d18:0/18:0, d19:0/17:0) and higher Type 2 diabetes risk, whereas creatine, glycine, 1-linoleoyl-GPC (18:2), 1-palmitoyl-2-oleoyl-GPE, 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) and 1-stearoyl-2-oleoyl-GPE (18:0/18:1) were protective. CONCLUSIONS:Disruptions in rhythmic metabolites are implicated in Type 2 diabetes pathophysiology through specific metabolic pathways, highlighting the potential for biomarkers to support circadian-based prevention strategies.

This study investigated diffusion tensor imaging (DTI) derived macro- and micro-structural musculoskeletal adaptations in forearm flexor muscles in individuals with hemiparetic cerebral palsy (HCP) and typically developing (TD) individuals, and their relationship to reduced grip strength. In 14 individuals with HCP and 16 TD individuals, T1-weighted and diffusion-weighted magnetic resonance images of both forearms were acquired, and maximum grip strength was measured. In two forearm flexors, muscle volume, DTI-based diffusivity metrics, and probabilistic tractography derived fascicle architecture was estimated. Linear mixed-effects models evaluated interlimb differences in structural parameters and their impact on grip strength. In the HCP group, paretic muscles showed significant reductions in volume, diffusivity values, fascicle lengths, and physiological cross-sectional area as compared to nonparetic forearm and TD participants. Furthermore, reduced muscle volume and diffusivity together explained 62% of the grip strength deficit. These findings demonstrate that decreased muscle volume and altered microstructure, as indicated by reduced diffusivity, contribute significantly to functional impairments in HCP. DTI-based diffusivity metrics non-invasively reveal crucial insights into pathophysiological changes in muscle tissue, such as muscle atrophy and fibrosis. Future therapies should focus on both muscle macro- and micro-structural adaptations as targets to improve motor function in HCP.

This study aimed to characterize interlimb differences in passive torques (PT) at the wrist and metacarpophalangeal (MCP) joints in individuals with hemiparetic cerebral palsy (HCP), and to relate them to previously acquired diffusion tensor imaging (DTI)-derived diffusivity measures in forearm flexor muscles. In 10 individuals (5F, 18.14±8.7 years) with HCP, a custom-built device was used to measure the PTs produced by the wrist and MCP joints of both limbs in 16 discrete hand configurations. Interlimb differences in wrist and finger PT showed significant increases with extreme wrist and finger extension and severity of HCP. Furthermore, increased interlimb differences in PT during extreme wrist and finger extension were significantly correlated with DTI-derived diffusivity estimates, indicating that underlying structural muscle changes are related to increased PTs in extended hand configurations.Clinical Relevance— These findings establish that intrinsic forearm muscle adaptations significantly and negatively influence passive biomechanical properties when individuals with HCP extend their wrist/fingers to the end of their passive range of motion.

Introduction: Intimate Partner Violence (IPV) is recognized as a public health problem that has profound negative consequences for physical and mental health and well-being. Previous research has focused primarily on physical and sexual IPV; non-physical IPV has been understudied, particularly among men. Methods: Using data from Statistic Canada's 2018 Survey of Safety in Public and Private Spaces, we examined associations between non-physical IPV and nine heath status variables: fair/poor mental health, fair/poor general health, dissatisfaction with life, pain, use of medication, suicidal thoughts, mood disorder, anxiety disorder, and PTSD. Results: Women (13.3 %) and men (12.6 %) were equally likely to report non-physical IPV in the past year, often without co-occurring physical/sexual IPV. Bivariate analyses revealed that non-physical IPV increased the risk of reporting all negative health status variables except pain. When associations were examined in relation to the frequency of non-physical IPV, a gradient was observed. In multivariable analyses that controlled for potential confounders, most associations observed in the bivariate analyses persisted, but associations were somewhat attenuated when controlling for co-occurring physical/sexual IPV. Conclusions: Non-physical IPV, particularly if it happens frequently, is strongly associated with negative health, often independent of co-occurring physical/sexual IPV. Longitudinal studies have found that non-physical IPV is a predictor of subsequent physical/sexual IPV, further increasing the risk of negative health. This underscores the importance of specifically addressing non-physical IPV through public health prevention programs and the need for it to be recognized as a form of IPV that is as important as physical and sexual IPV.

Triple P is a multilevel parenting program aimed at promoting children’s emotional, social, and behavioural competence and preventing behavioural problems through supporting parents in positive parenting. Examine the rollout of the Triple P system parenting program on child maltreatment rates in Manitoba, Canada, using administrative data analysis and document review of policies and programs. This population-based retrospective cohort study included 962,170 children aged 18 years or younger. Administrative healthcare and social services data from the Manitoba Population Research Data Repository were used to compare child maltreatment indicators before (1989–2004) and after (2005–2018) Triple P implementation. Compared to before Triple P implementation, injury hospitalization rates were lower in the early (2005–2011) and later (2012–2018) periods of implementation. Maltreatment hospitalization and violent death rates were not statistically different in the early period, but they were lower in the later period of Triple P implementation. The interrupted time-series analysis showed that after Triple P intervention in 2005, injury hospitalization rates increased until 2012, followed by a gradual decline through 2018, compared to the expected trend without the intervention. Maltreatment hospitalization trends displayed a decline until 2012, followed by an increase, and then a gradual decline from 2014 to 2018 relative to the anticipated trend without the intervention. These trends varied by age, sex, income quintiles, and region. Triple P is one of several programs that may have contributed to reductions in child maltreatment rates observed in Manitoba since the implementation of the program.

INTRODUCTION:A history of childhood maltreatment is associated with increased risk of psychological and cognitive difficulties as well as stress dysregulation in adulthood; however, less is known about the impacts during pregnancy. The objectives of this study were to explore the association between a history of childhood maltreatment and 1) prenatal stress and 2) executive functioning among pregnant girls and young women. METHODS:Cross-sectional data from the Healthy Foundations Study, including participants aged 14-24 years were used [n = 254; a sub-study of the British Columbia Healthy Connections Project (BCHCP)]. The BCHCP was a randomized controlled trial of the Nurse-Family Partnership (NFP) program in Canada. The Childhood Trauma Questionnaire was used to measure total cumulative childhood maltreatment, as well as dimensions of threat and deprivation. Chronic stress was measured using prenatal hair cortisol, and executive functioning was measured using two standardized tests. All measures were taken at baseline prior to randomization. Linear regression was used to estimate beta coefficients and 95 % confidence intervals (CIs). RESULTS:A high proportion, approximately 55 %, of participants reported a history of moderate to extreme childhood maltreatment. Total cumulative childhood maltreatment was associated with increased prenatal hair cortisol concentration (b = 0.27; 95 % CI: 0.03-0.51), but not executive functioning (b = 0.02; 95 % CI: -0.07-0.11). No moderation was found by psychological resources or distress (p > 0.05). CONCLUSION:A history of childhood maltreatment was significantly associated with increased prenatal hair cortisol but not executive functioning among this sample of disadvantaged pregnant girls and young women in Canada. Further research is needed to inform efforts to prevent childhood maltreatment and to inform NFP refinements to better address early child adversities.

During the COVID-19 pandemic, neighbourhoods with high material deprivation and high proportions of racialized Canadians were disproportionately affected by COVID-19. Many of these neighbourhoods were served by community hospitals. We sought to compare the burden of COVID-19 care in community and academic intensive care units (ICUs) in Ontario, Canada. We included all adult patients admitted to Ontario ICUs with COVID-19 between 1 March 2020 and 31 July 2021 in a retrospective cohort study. We compared patient volumes, demographics, interventions, and outcomes between community hospital corporations (CHCs) and academic hospital corporations (AHCs). During the first three waves of the pandemic, 9,651 adult ICU admissions for COVID-19 were reported across 72 hospital corporations in Ontario: 6,902 (71.5

BACKGROUND Neighborhood deprivation and depression have been linked to epigenetic age acceleration. The next-generation epigenetic clocks including the DNA methylation (DNAm) GrimAge, and PhenoAge have incorporated clinical biomarkers of physiological dysregulation by selecting cytosine-phosphate-guanine sites that are associated with risk factors for disease, and have shown improved accuracy in predicting morbidity and time-to-mortality compared to the first-generation clocks. The aim of this study is to examine the association between neighborhood deprivation and DNAm GrimAge and PhenoAge acceleration in adults, and assess interaction with depressive symptoms. METHODS The Canadian Longitudinal Study on Aging recruited 51 338 participants aged 45-85 years across provinces in Canada. This cross-sectional analysis is based on a subsample of 1 445 participants at baseline (2011-2015) for whom epigenetic data were available. Epigenetic age acceleration (years) was assessed using the DNAm GrimAge and PhenoAge, and measured as residuals from regression of the biological age on chronological age. RESULTS A greater neighborhood material and/or social deprivation compared to lower deprivation (b = 0.66; 95% confidence interval [CI] = 0.21, 1.12) and depressive symptoms scores (b = 0.07; 95% CI = 0.01, 0.13) were associated with higher DNAm GrimAge acceleration. The regression estimates for these associations were higher but not statistically significant when epigenetic age acceleration was estimated using DNAm PhenoAge. There was no evidence of a statistical interaction between neighborhood deprivation and depressive symptoms. CONCLUSIONS Depressive symptoms and neighborhood deprivation are independently associated with premature biological aging. Policies that improve neighborhood environments and address depression in older age may contribute to healthy aging among older adults living in predominantly urban areas.

Objectives Guided by the bioecological model, the purpose of this study was to examine the associations of (1) individual level factors (sociodemographic, health behaviour and mental health), (2) family (micro) level COVID-19 experiences (difficulty with household management, managing child mood and behaviour, and pandemic-related positive experiences) and (3) community (macro) level factors (residential instability, ethnic concentration, material deprivation and dependency, an indicator of age and labour force) with harsh parenting practices and inter-partner conflict during the early lockdown of the COVID-19 pandemic in Ontario, Canada. Design A cross-sectional analysis of data from the Ontario Parent Survey. Setting A convenience sample of 7451 caregivers living in Ontario, Canada, at the time of baseline data collection (May–June 2020). Participants Caregivers aged 18 years and older with children 17 years or younger. Outcome measures Parenting practices over the past 2 months was assessed using a published modification of the Parenting Scale. The frequency of inter-partner conflict over the past month was assessed using the Marital Conflict scale. Results Individual (sociodemographic factors, alcohol use, and higher depressive and anxiety symptoms) and family (difficulties with managing the household and child mood and behaviour) level factors were positively associated with inter-partner conflict and harsh parenting practices. Having fewer positive experiences (eg, performing activities with children), and economic adversity at the family level were positively associated with inter-partner conflict but inversely associated with harsh parenting. At the community level, residential instability was negatively associated with harsh parenting practices. Conclusions Individual and family level factors were associated with harsh parenting and inter-partner conflict. The associations of fewer positive experiences and economic hardship with harsh parenting practices may be more complex than initially thought. Efforts that raise awareness and address caregiver mental health concerns are needed as part of the pandemic response to promote positive inter-partner and parent-child interactions.

PURPOSE:To determine the sensitivity profiles of probabilistic and deterministic DTI tractography methods in estimating geometric properties in arm muscle anatomy. METHODS:Spin-echo diffusion-weighted MR images were acquired in the dominant arm of 10 participants. Both deterministic and probabilistic tractography were performed in two different muscle architectures of the parallel-structured biceps brachii (and the pennate-structured flexor carpi ulnaris. Muscle fascicle geometry estimates and number of fascicles were evaluated with respect to tractography turning angle, polynomial fitting order, and SNR. The DTI tractography estimated fascicle lengths were compared with measurements obtained from conventional cadaveric dissection and ultrasound modalities. RESULTS:The probabilistic method generally estimated fascicle lengths closer to ranges reported by conventional methods than the deterministic method, most evident in the biceps brachii (p > 0.05), consisting of longer, arc-like fascicles. For both methods, a wide turning angle (50º-90°) generated fascicle lengths that were in close agreement with conventional methods, most evident in the flexor carpi ulnaris (p > 0.05), consisting of shorter, feather-like fascicles. The probabilistic approach produced at least two times more fascicles than the deterministic approach. For both approaches, second-order fitting yielded about double the complete tracts as third-order fitting. In both muscles, as SNR decreased, deterministic tractography produced less fascicles but consistent geometry (p > 0.05), whereas probabilistic tractography produced a consistent number but altered geometry of fascicles (p < 0.001). CONCLUSION:Findings from this study provide best practice recommendations for implementing DTI tractography in skeletal muscle and will inform future in vivo studies of healthy and pathological muscle structure.

AbstractBackgroundAdverse childhood experiences (ACEs) are associated with multimorbidity in adulthood. This link may be mediated by psychosocial and biological factors, but evidence is lacking. The current study evaluates this mediation model.MethodWe analyzed data from the Canadian Longitudinal Study of Aging (N= 27 170 community participants). Participants were 45–85 years at recruitment, when allostatic load and social engagement data were collected, and 3 years older at follow-up, when ACEs and multimorbidity data were collected. Structural equation modeling was used to test for mediation in the overall sample, and in sex- and age-stratified subsamples, all analyses adjusted for concurrent lifestyle confounds.ResultsIn the overall sample, ACEs were associated with multimorbidity, directly,β= 0.12 (95% confidence interval 0.11–0.13) and indirectly. Regarding indirect associations, ACEs were related to social engagement,β= −0.14 (−0.16 to −0.12) and social engagement was related to multimorbidity,β= −0.10 (−0.12 to −0.08). ACEs were related to allostatic load,β= 0.04 (0.03–0.05) and allostatic load was related to multimorbidity,β= 0.16 (0.15–0.17). The model was significant for males and females and across age cohorts, with qualifications in the oldest stratum (age 75–85).ConclusionsACEs are related to multimorbidity, directly and via social engagement and allostatic load. This is the first study to show mediated pathways between early adversity and multimorbidity in adulthood. It provides a platform for understanding multimorbidity as a lifespan dynamic informing the co-occurrence of the varied disease processes represented in multimorbidity.

Research examining the association between exposure to a wide range of adverse childhood experiences (ACEs) and accelerated biological aging in older adults is limited. The purpose of this study was to examine the association of ACEs, both as a cumulative score and individual forms of adversity, with epigenetic age acceleration assessed using the DNA methylation (DNAm) GrimAge and DNAm PhenoAge epigenetic clocks in middle and older‐aged adults. This cross‐sectional study analyzed baseline and first follow‐up data on 1445 participants aged 45–85 years from the Canadian Longitudinal Study on Aging (CLSA) who provided blood samples for DNAm analysis. ACEs were assessed using a validated self‐reported questionnaire. Epigenetic age acceleration was estimated by regressing each epigenetic clock estimate on chronological age. Cumulative ACEs score was associated with higher DNAm GrimAge acceleration (β: 0.07; 95% CI: 0.02, 0.11) after adjusting for covariates. Childhood exposure to parental separation or divorce (β: 0.06; 95% CI: 0.00, 0.11) and emotional abuse (β: 0.06; 95% CI: 0.00, 0.12) were associated with higher DNAm GrimAge acceleration after adjusting for other adversities and covariates. There was no statistical association between ACEs and DNAm PhenoAge acceleration. Early life adversity may become biologically embedded and lead to premature biological aging, in relation to DNAm GrimAge, which estimates risk of mortality. Strategies that increase awareness of ACEs and promote healthy child development are needed to prevent ACEs.

Unilateral brain injuries occurring before at or shortly after full-term can result in hemiplegic cerebral palsy (HCP). HCP affects one side of the body and can be characterized in the hand with measures of weakness and a loss of independent hand control resulting in mirror movements. Hand impairment severity is extremely heterogeneous across individuals with HCP and the neural basis for this variability is unclear. We used diffusion MRI and tractography to investigate the relationship between structural morphology of the supraspinal corticospinal tract (CST) and the severity of two typical hand impairments experienced by individuals with HCP, grasp weakness and mirror movements. Results from nine children with HCP and eight children with typical development show that there is a significant hemispheric association between CST microstructure and hand impairment severity that may be explained by atypical development and fiber distribution of motor pathways. Further analysis in the non-lesioned (dominant) hemisphere shows significant differences for CST termination in the cortex between participants with HCP and those with typical development. These findings suggest that structural disparities at the cellular level in the seemingly unaffected hemisphere after early unilateral brain injury may be the cause of heterogeneous hand impairments seen in this population.Clinical Relevance— Quantitative measurement of the variability in hand function in individuals with HCP is necessary to represent the distinct impairments experienced by each person. Further understanding of the structural neural morphology underlying distal upper extremity motor deficits after early unilateral brain injury will help lead to the development of more specific targeted interventions that increase functional outcomes.

IMPORTANCE The association of COVID-19 not requiring hospitalization with functional mobility in community-dwelling adults above and beyond the impact of the pandemic control measures implemented in 2020 remains to be elucidated. OBJECTIVE To evaluate the association between a COVID-19 diagnosis and change in mobility and physical function of adults in Canada aged 50 years or older during the initial pandemic lockdown. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used data from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 study. This study was launched on April 15, 2020, and the exit questionnaires were completed between September and December 2020. Prepandemic data from the first CLSA follow-up (2015-2018) were also used. Respondents included middle-aged and older community-dwelling participants residing in Canadian provinces. Datawere analyzed from February toMay 2021. EXPOSURES The assessment for self-reported COVID-19 status was adapted from the Public Health Agency of Canada and the Centers for Disease Control and Prevention case definition available at the time of data collection; caseswere classified as confirmed or probable, suspected, or non-COVID-19. MAIN OUTCOMES AND MEASURES Changes in mobility since the start of the COVID-19 pandemic were assessed using global rating of change in mobility scales at the COVID-19 exit questionnaire. Participant-reported new onset of difficulty in 3 physical function tasks was also examined. RESULTS Among 51 338 participants at baseline, 21 491 participants (41.9%) were 65 years or older and 26 155 participants (51.0%) were women and 25 183 (49.1%) were men. Of 2748 individuals with confirmed or probable or suspected COVID-19, 113 (94.2%) were not hospitalized. Individuals with confirmed or probable COVID-19 had higher odds of worsening mobility in terms of ability to engage in household activity (odds ratio [OR], 1.89; 95% CI, 1.11-3.22), physical activity (OR, 1.91; 95% CI, 1.32-2.76), and standing up after sitting in a chair (OR, 2.33; 95% CI, 1.06-5.11) compared with adults without COVID-19 during the same pandemic time period. Similar results were found for suspected COVID-19 status (eg, household activity: OR, 2.09; 95% CI, 1.82-2.41). CONCLUSIONS AND RELEVANCE This cohort study among older adults in Canada found that receiving a COVID-19 diagnosis was significantly associated with worse mobility and functioning outcomes even in the absence of hospitalization. These findings suggest that interventions may be needed for individuals with mild to moderate COVID-19 who do not require hospitalization.

WASH (water, sanitation, and hygiene) has become the most crucial amenity in the past decade for every individual on the planet. In the UN agenda for 2030, which created 17 Sustainable Development Goals (SDGs), SDGs 3, 4, and 6 directly correlate with WASH practices and management for creating a good health hygiene environment for all. The dearth of WASH facilities has created barriers for averting the transmission of COVID-19, motivating the concept of WASH as the primary step of precaution and prevention, which includes WASH practices, communication for literacy, and positive behavioral changes primarily in developing and low-income countries. This Review deals with the complex concept of correlation of WASH and SDGs 3, 4, and 6 while defining elaborate WASH practices, including the prominence of clean water, the need for sanitation facilities, and health hygiene for good health and immunity for preparedness for and during epidemics and pandemics. Certain risk factors explain the sectors in which the gaps exist, creating a gap for implementation of WASH practices in epidemics and pandemics across the globe. Further, COVID-19 surge succession is presented along with data of different variants that have occurred. The need of WASH understanding is required using different tools (audio-visual, social media, print media, and mass media) and strategies (communication, advocacy, and positive behavioral changes) for every individual as an act to counter consequences during and after the COVID-19 pandemic and as a routine practice for future preparedness. This Review gives a detailed concept of WASH understanding for every sector from community to government agencies and research professionals to act immediately for the sustainable future of humanity.

Importance The measurement of laboratory biomarkers plays a critical role in managing patients with COVID-19. However, to date most systematic reviews examining the association between laboratory biomarkers and mortality in hospitalized patients early in the pandemic focused on small sets of biomarkers, did not account for multiple studies including patients within the same institutions during overlapping timeframes, and did not include a significant number of studies conducted in countries other than China. Objective To provide a comprehensive summary and an evidence map examining the relationship between a wide range of laboratory biomarkers and mortality among patients hospitalized with COVID-19 during the early phase of the pandemic in multiple countries. Evidence review MEDLINE, EMBASE, and Web of Science were searched from Dec 2019 to March 9, 2021. A total of 14,049 studies were identified and screened independently by two raters; data was extracted by a single rater and verified by a second. Quality was assessed using the Joanna Briggs Institute (JBI) Case Series Critical Appraisal tool. To allow comparison across biomarkers, standardized mean differences (SMD) were used to quantify the relationship between laboratory biomarkers and hospital mortality. Meta-regression was conducted to account for clustering within institutions and countries. Results Our systematic review included 94 case-series studies from 30 countries. Across all biomarkers, the largest and most precise SMDs were observed for cardiac (troponin (1.03 (95% CI 0.86 to 1.21)), and BNP/NT-proBNP (0.93 (0.52 to 1.34)), inflammatory (IL-6 (0.97 (0.67 to 1.28) and Neutrophil-to-lymphocyte ratio (0.94 (0.59 to 1.29)), and renal biomarkers (blood urea nitrogen (1.01 (0.79 to 1.23)) and estimated glomerular filtration rate (-0.96 (-1.42 to -0.50)). There was heterogeneity for most biomarkers across countries with studies conducted in China generally having larger effect sizes. Conclusions and relevance The results of this study provide an early pandemic summary of the relationship between biomarkers and mortality in hospitalized patients. We found our estimated ESs were generally attenuated compared to previous systematic reviews which predominantly included studies conducted in China. Despite using sophisticated methodology to examine studies across countries, heterogeneity in reporting of case-series studies early in the pandemic limits clinical interpretability.

Maternal exposure to childhood maltreatment (CM) is associated with offspring behavioral problems; however, little work has examined these associations longitudinally across child development. This study examined the effects of maternal history of CM on trajectories of child internalizing and externalizing behavior measured from toddlerhood to preschool, and the role of maternal depressive symptoms and parenting behavior as potential mediators. Participants included 115 mother-child dyads recruited from a hospital maternity ward. Maternal CM was measured at 3-months postpartum. At 18, 36, and 60 months, maternal depressive symptoms and child behavior were assessed via maternal report and parenting behavior was assessed through direct observation. Findings indicated that children of mothers exposed to CM demonstrated poorer trajectories of problem behavior across early childhood. Maternal depressive symptoms mediated the relation between CM and children's internalizing problems. Findings highlight the importance of screening for maternal depressive symptoms and early intervention for maternal and child mental health.