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Tetyana Kendzerska,1– 3 David T Zhu,1,4 Andrea S Gershon,5 Jodi D Edwards,3,6 Cayden Peixoto,7 Rebecca Robillard,8 Claire E Kendall1,7,9,10 1Clinical Epidemiology Program, The Ottawa Hospital Research Institute/The Ottawa Hospital, Ottawa, Ontario, Canada; 2Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 3School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; 4Faculty of Science, Western University, London, Ontario, Canada; 5Department of Medicine, Sunnybrook Health Sciences Centre/University of Toronto, Toronto, Ontario, Canada; 6University of Ottawa Heart Institute, Ottawa, Ontario, Canada; 7The Institut Du Savoir Montfort, Ottawa, Ontario, Canada; 8The Royal’s Institute of Mental Health Research/University of Ottawa, Ottawa, Ontario, Canada; 9C.T. Lamont Primary Health Care Research Group, Bruyère Research Institute, Ottawa, Ontario, Canada; 10Department of Family Medicine, University of Ottawa, Ottawa, Ontario, CanadaCorrespondence: Tetyana KendzerskaThe Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, CanadaTel +1 613-761-4636Email tkendzerska@toh.caBackground: Individuals with chronic conditions require ongoing disease management to reduce risks of adverse health outcomes. During the COVID-19 pandemic, health care for non-COVID-19 cases was affected due to the reallocation of resources towards urgent care for COVID-19 patients, resulting in inadequate ongoing care for chronic conditions.Methods: A keyword search was conducted in PubMed, Google Scholar, Science Direct, and Scopus for English language articles published between January 2020 and January 2021.Findings: During the COVID-19 pandemic, in-person care for individuals with chronic conditions have decreased due to government restriction of elective and non-urgent healthcare visits, greater instilled fear over potential COVID-19 exposure during in-person visits, and higher utilization rates of telemedicine compared to the pre-COVID-19 period. Potential benefits of a virtual-care framework during the pandemic include more effective routine disease monitoring, improved patient satisfaction, and increased treatment compliance and follow-up rates. However, more needs to be done to ensure timely and effective access to telemedicine, particularly for individuals with lower digital literacy. Capitation primary care models have been proposed as a more financially-robust approach during the COVID-19 pandemic than fee-for-service primary care models; however, the interplay between different primary models and the health outcomes is still poorly understood and warrants further investigation. Shortages of medication used to manage chronic conditions were also observed at the beginning of the COVID-19 pandemic due to global supply chain disruptions. Finally, patients with chronic conditions faced lifestyle disruptions due to the COVID-19 pandemic, specifically in physical activity, sleep, stress, and mental health, which need to be better addressed.Interpretation: Overall, this review elucidates the disproportionately greater barriers to primary and specialty care that patients with chronic diseases face during the COVID-19 pandemic and emphasizes the urgent need for better chronic disease management strategies moving forward.Keywords: narrative review, chronic disease, COVID-19 pandemic, primary care, specialist care

Objective: To estimate the prevalence of chronic conditions among children admitted to U.S. pediatric intensive care units and to assess whether patients with complex chronic conditions experience pediatric intensive care unit mortality and prolonged length of stay risk beyond that predicted by commonly used severity-of-illness risk-adjustment models.Design, Setting, and Patients: Retrospective cohort analysis of 52,791 pediatric admissions to 54 U.S. pediatric intensive care units that participated in the Virtual Pediatric Intensive Care Unit Systems database in 2008.Measurements: Hierarchical logistic regression models, clustered by pediatric intensive care unit site, for pediatric intensive care unit mortality and length of stay >15 days. Standardized mortality ratios adjusted for severity-of-illness score alone and with complex chronic conditions.Main Results: Fifty-three percent of pediatric intensive care unit admissions had complex chronic conditions, and 18.5% had noncomplex chronic conditions. The prevalence of these conditions and their organ system subcategories varied considerably across sites. The majority of complex chronic condition subcategories were associated with significantly greater odds of pediatric intensive care unit mortality (odds ratios 1.25-2.9, all p values < .02) compared to having a noncomplex chronic condition or no chronic condition, after controlling for age, gender, trauma, and severity-of-illness. Only respiratory, gastrointestinal, and rheumatologic/orthopedic/psychiatric complex chronic conditions were not associated with increased odds of pediatric intensive care unit mortality. All subcategories were significantly associated with prolonged length of stay. All noncomplex chronic condition subcategories were either not associated or were negatively associated with pediatric intensive care unit mortality, and most were not associated with prolonged length of stay, compared to having no chronic conditions. Among this group of pediatric intensive care units, adding complex chronic conditions to risk-adjustment models led to greater model accuracy but did not substantially change unit-level standardized mortality ratios.Conclusions: Children with complex chronic conditions were at greater risk for pediatric intensive care unit mortality and prolonged length of stay than those with no chronic conditions, but the magnitude of risk varied across subcategories. Inclusion of complex chronic conditions into models of pediatric intensive care unit mortality improved model accuracy but had little impact on standardized mortality ratios. [ABSTRACT FROM AUTHOR]

Five-year driving habit trajectories among older adults (n = 645) at-risk for crashes were examined. Performance measures included Useful Field of View (UFOV). Motor-Free Visual Perception Test, Rapid Walk, and Foot Tap. Self-report measures included demographics and the Driving Habits Questionnaire. Longitudinal random-effects models revealed that drivers at-risk for subsequent crashes, based upon UFOV, regulated their driving more than the lower-risk participants. Restricted driving was present at baseline for the at-risk group and was observed in longitudinal trajectories that controlled for baseline differences. Results indicate that persons at-risk for subsequent crashes increasingly limit their driving over time. Despite this self-regulation, a larger sample of such older drivers was twice as likely to incur subsequent at-fault crashes. Results suggest that self-regulation among older drivers at-risk for crashes is an insufficient compensatory approach to eliminating increased crash risk. UFOV is a registered trademark of Visual Awareness, Inc. [ABSTRACT FROM AUTHOR]

We combined data from six studies, all using the same speed of processing training program, to examine the mechanisms of training gain and the impact of training on cognitive and everyday abilities of older adults. Results indicated that training produces immediate improvements across all subtests of the Useful Field of View test, particularly for older adults with initial speed of processing deficits. Age and education had little to no impact on training gain. Participants maintained benefits of training for at least 2 years, which translated to improvements in everyday abilities, including efficient performance of instrumental activities of daily living and safer driving performance. [ABSTRACT FROM AUTHOR]

The supracondylar process of the humerus is a rare abnormality found in 0.4-2.7% of the population. It has been documented to cause neurovascular compression in the upper extremity owing to its local impingement on the median nerve and brachial artery at its medial location on the humerus just proximal to the elbow. The authors report the first known case of digital ischemia from embolization of thrombus caused by local compression of the brachial artery attributed to a supracondylar process. [ABSTRACT FROM AUTHOR]

We examined the physical, visual, health, and cognitive abilities of 1,656 older adults as prospective predictors of self-reported driving cessation over a 5-year period. We examined the time to driving cessation across 5 years after we controlled for days driven per week at baseline and any cognitive intervention participation. Older age, congestive heart failure, and poorer physical performance (according to the Turn 360 Test) were statistically significant risk factors for driving cessation. Slower speed of processing (according to the Digit Symbol Substitution and Useful Field of View tests) was a significant risk factor even after we took baseline driving, age, health, vision, and physical performance into consideration. Implications are that assessments of cognitive speed of processing can provide valuable information about the subsequent risk of driving cessation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) can cause cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, and nasal colonization with this pathogen increases the risk of infection. Due to its high negative predictive value, multiple studies support using the MRSA nasal polymerase chain reaction (PCR) test to discontinue antimicrobials that target MRSA in the setting of a negative test result. The purpose of this project was to assess the utility of a protocol to allow pharmacists the ability to order MRSA nasal PCR screenings in hospitalized patients with pneumonia. Results : The pre-protocol group included a random sample of 100 patients, and the post-protocol group included 625 patients. Vancomycin DOTs when pharmacists ordered PCRs were significantly lower compared to the pre-protocol group ( p < 0.5; 95% CI, 0.46-2.24). The average length of stay and readmission rates at 30 days were significantly lower in the post-protocol group compared to the pre-protocol group ( p < 0.05 and p = 0.02, respectively), but there was no significant difference in mortality ( p = 0.33). Methods : A protocol was implemented at our institution that allowed pharmacists to order an MRSA nasal PCR test in patients with pneumonia. This retrospective chart review compared a cohort of patients who received vancomycin from before implementation of the protocol to patients who received vancomycin after the protocol's implementation. The primary endpoint was vancomycin days of therapy (DOTs) between the pre-protocol group and the post-protocol group. Other endpoints assessed included the length of hospitalization, readmission rates, and mortality. Conclusions : Pharmacists ordering MRSA nasal PCR tests significantly reduced vancomycin DOTs, average length of stay, and 30-day readmission rates, contributing to positive outcomes in patients with pneumonia.

Aim: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis., Methods: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes., Results: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05)., Conclusion: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Results from randomized trials suggest benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation in clinically stable acute heart failure. We aim to examine the real-world effectiveness of early versus delayed post-discharge SGLT2 inhibitor initiation in people with acute heart failure and type 2 diabetes., Methods and Results: Using linkable administrative databases in Ontario, Canada, individuals aged 66 years or older with type 2 diabetes who were discharged to the community from acute care hospitals for heart failure between 1 July 2016 and 31 March 2020 were included in this retrospective, population-based cohort study. The primary outcome was hospitalization for heart failure (HHF) or cardiovascular mortality as a composite. Follow-up started from discharge for maximum 1 year. We compared outcomes between post-discharge SGLT2 inhibitor initiation within 3 days, 4-90 days, or 91-180 days, versus delayed initiation for at least 180 days. The 'clone-censor-weight' approach with a target trial emulation framework was used to address time-related biases. There were 9641 eligible individuals. After cloning and artificial censoring, there were 38 564 clones, 12 439 person-years, and 7584 events. Compared to delayed initiation for at least 180 days, initiation within 3 days post-discharge was associated with a lower 1-year risk of HHF or cardiovascular mortality (risk ratio [RR] 0.65, 95% confidence interval [CI] 0.45-0.83), while initiation 4-90 days (RR 0.83, 95% CI 0.72-0.93) or 91-180 days (RR 0.89, 95% CI 0.79-0.97) showed smaller risk reduction., Conclusion: Real-world evidence supports early SGLT2 inhibitor initiation to reduce HHF or cardiovascular mortality in acute heart failure and type 2 diabetes., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Impairments of hearing and auditory processing (AP) have been indicated as risk factors for dementia, but it remains unclear if persons with clinically diagnosed mild cognitive impairment (MCI) show such impairments. The objective of these analyses was to compare AP between those with and without a clinical diagnosis of MCI using a battery of AP measures., Method: Data from 274 older adults from the Keys to Staying Sharp randomized clinical trial (NCT03528486) were analyzed. A battery of AP measures in which three domains (temporal processing, binaural processing, and degraded speech understanding) were addressed by six tests was administered. Analyses were registered at https://osf.io/nga4v., Results: Those with and without a clinical diagnosis of MCI differed significantly in age, p = .002; pure-tone hearing in the left ear, p = .007; sex, p = .015; and race, p < .001. These covariates were included in multivariate analysis of covariance, which indicated significant differences between persons with and without MCI on measures of binaural processing ( p s ≤ .006), but not on measures of temporal processing or degraded speech ( p s ≥ .093). Pure-tone hearing averages did not significantly differ among those with or without MCI after adjusting for age, sex, and race ( p s ≥ .292)., Conclusions: AP in the binaural domain is impaired in MCI, but peripheral hearing did not significantly differ between those with and without MCI. Poor performance on AP measures of binaural processing may reflect problems dividing attention and may be indicative of dementia risk. Results have clinical implications for early detection of and intervention for cognitive impairment.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in dementia-free adults aged 60-64 years from the UK Biobank. We then estimated associations between these profiles with incident dementia, cognition, and neuroimaging outcomes, and explored the differences across profiles in the effects of a polygenic risk score for Alzheimer's disease on outcomes. In 55,333 males and 63,063 females, three sex-specific latent profiles were identified: cardiometabolic risk, substance use-related risk, and low risk. The cardiometabolic risk profile in both males and females was associated with greater incidence of all-cause dementia (male: OR [95% CI] = 2.33 [2.03, 2.66]; female: OR [95% CI] = 1.44 [1.24, 1.68]), poorer cognitive performance, greater brain atrophy, and greater white matter hyperintensity volume compared to the low risk profile. The substance use-related risk profile in males was associated with poorer cognitive performance and greater white matter hyperintensities compared to the low risk profile, but no difference in all-cause dementia incidence was observed (OR [95% CI] = 1.00 [0.95, 1.06]). In females, the substance use-related risk profile demonstrated increased dementia incidence (OR [95% CI] = 1.58 [1.57, 1.58]) and greater brain atrophy but smaller white matter hyperintensity volume compared to the low risk profile. The polygenic risk score had larger effects among females, and differentially influenced outcomes across profiles; for instance, there were larger effects of the polygenic risk score on atrophy in the cardiometabolic profile vs. the low risk profile among males, and larger effects of the polygenic risk score on loss of white matter integrity in the cardiometabolic profile vs. the low risk profile among females. These results reveal three modifiable dementia risk profiles, their unique cognitive/neuroimaging outcomes, and their interactions with genetic risk for Alzheimer's disease. These differences highlight the need to consider population heterogeneity in risk prediction tools and in planning personalized prevention strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The purpose of this study was to investigate relationships between depressive symptoms, functional disability, and physical activity over time in community-dwelling older adults. The Religious Order Study and Rush Memory and Aging Project are longitudinal cohort studies based in the United States which began recruitment in 1994 and 1997, respectively. This analysis included 1611 participants (27.4% male, 92.9% White, 74.7% cognitively normal) who were included at age 80 and followed until age 90. Depressive symptoms were assessed using the modified Center for Epidemiologic Studies Depression scale. Functional disability was assessed using the Instrumental Activities of Daily Living (IADL) scale. Physical activity was self-reported hours of weekly exercise. Reciprocal temporal relationships between these variables were investigated using a random intercept cross-lagged panel model, which decomposes observed variables into stable between-person ('trait') and variable within-person ('state') components to estimate the directional effects between variables over time. Traits for depressive symptoms, IADL disability, and physical activity were correlated. IADL disability showed autoregressive effects; disability starting at age 82 strongly predicted subsequent disability. Consistent autoregressive effects were not observed for depressive symptoms nor physical activity. Several small cross-lagged effects between states were observed for IADL disability and physical activity, as well as for IADL disability and depressive symptoms. There were no direct effects between depressive symptoms and physical activity, but several paths through IADL disability were observed between ages 82 and 88. Functional disability played an important role in octogenarians, highlighting the importance of maintaining functional independence later in life., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

We consider state and parameter estimation for compartmental models having both time-varying and time-invariant parameters. In this manuscript, we first detail a general Bayesian computational framework as a continuation of our previous work. Subsequently, this framework is specifically tailored to the susceptible-infectious-removed (SIR) model which describes a basic mechanism for the spread of infectious diseases through a system of coupled nonlinear differential equations. The SIR model consists of three states, namely, the susceptible, infectious, and removed compartments. The coupling among these states is controlled by two parameters, the infection rate and the recovery rate. The simplicity of the SIR model and similar compartmental models make them applicable to many classes of infectious diseases. However, the combined assumption of a deterministic model and time-invariance among the model parameters are two significant impediments which critically limit their use for long-term predictions. The tendency of certain model parameters to vary in time due to seasonal trends, non-pharmaceutical interventions, and other random effects necessitates a model that structurally permits the incorporation of such time-varying effects. Complementary to this, is the need for a robust mechanism for the estimation of the parameters of the resulting model from data. To this end, we consider an augmented state vector, which appends the time-varying parameters to the original system states whereby the time evolution of the time-varying parameters are driven by an artificial noise process in a standard manner. Distinguishing between time-varying and time-invariant parameters in this fashion limits the introduction of artificial dynamics into the system, and provides a robust, fully Bayesian approach for estimating the time-invariant system parameters as well as the elements of the process noise covariance matrix. This computational framework is implemented by leveraging the robustness of the Markov chain Monte Carlo algorithm permits the estimation of time-invariant parameters while nested nonlinear filters concurrently perform the joint estimation of the system states and time-varying parameters. We demonstrate performance of the framework by first considering a series of examples using synthetic data, followed by an exposition on public health data collected in the province of Ontario., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Ectomycorrhizal (EM) associations can promote the dominance of tree species in otherwise diverse tropical forests. These EM associations between trees and their fungal mutualists have important consequences for soil organic matter cycling, yet the influence of these EM-associated effects on surrounding microbial communities is not well known, particularly in neotropical forests. We examined fungal and prokaryotic community composition in surface soil samples from mixed arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) stands as well as stands dominated by EM-associated Oreomunnea mexicana (Juglandaceae) in four watersheds differing in soil fertility in the Fortuna Forest Reserve, Panama. We hypothesized that EM-dominated stands would support distinct microbial community assemblages relative to the mixed AM-EM stands due to differences in carbon and nitrogen cycling associated with the dominance of EM trees. We expected that this microbiome selection in EM-dominated stands would lead to lower overall microbial community diversity and turnover, with tighter correspondence between general fungal and prokaryotic communities. We measured fungal and prokaryotic community composition via high-throughput Illumina sequencing of the ITS2 (fungi) and 16S rRNA (prokaryotic) gene regions. We analyzed differences in alpha and beta diversity between forest stands associated with different mycorrhizal types, as well as the relative abundance of fungal functional groups and various microbial taxa. We found that fungal and prokaryotic community composition differed based on stand mycorrhizal type. There was lower prokaryotic diversity and lower relative abundance of fungal saprotrophs and pathogens in EM-dominated than AM-EM mixed stands. However, contrary to our prediction, there was lower homogeneity for fungal communities in EM-dominated stands compared to mixed AM-EM stands. Overall, we demonstrate that EM-dominated tropical forest stands have distinct soil microbiomes relative to surrounding diverse forests, suggesting that EM fungi may filter microbial functional groups in ways that could potentially influence plant performance or ecosystem function., (© 2024. The Author(s).)

In this study, we model and predict rice yields by integrating molecular marker variation, varietal productivity, and climate, focusing on the Southern U.S. rice-growing region. This region spans the states of Arkansas, Louisiana, Texas, Mississippi, and Missouri and accounts for 85% of total U.S. rice production. By digitizing and combining four decades of county-level variety acreage data (1970 to 2015) with varietal information from genotyping-by-sequencing data, we estimate annual historical county-level allele frequencies. These allele frequencies are used together with county-level weather and yield data to develop ten machine learning models for yield prediction. A two-layer meta-learner ensemble model that combines all ten methods is externally evaluated against observations from historical Uniform Regional Rice Nursery trials (1980 to 2018) conducted in the same states. Finally, the ensemble model is used with forecasted weather from the Coupled Model Intercomparison Project across the 110 rice-growing counties to predict production in the coming decades for Composite Variety Groups assembled based on year of release, breeding program, and several breeding trends. Results indicate positive effects over time of public breeding on rice resilience to future climates, and potential reasons are discussed., Competing Interests: Competing interests statement:R.H. is currently employed by Bayer Crop Science but this is subsequent to her contributions to the project.

Background: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality, and their association with increased cardiovascular disease (CVD) risk represents a major public health concern. However, assessing CVD risk in women with a history of these conditions presents unique challenges, especially when studies are carried out using routinely collected data., Objectives: To summarise and describe key challenges related to the design and conduct of administrative studies assessing CVD risk in women with a history of HDP and provide concrete recommendations for addressing them in future research., Methods: This is a methodological guidance paper., Results: Several conceptual and methodological factors related to the data-generating mechanism and study conceptualisation, design/data management and analysis, as well as the interpretation and reporting of study findings should be considered and addressed when designing and carrying out administrative studies on this topic. Researchers should develop an a priori conceptual framework within which the research question is articulated, important study variables are identified and their interrelationships are carefully considered., Conclusions: To advance our understanding of CVD risk in women with a history of HDP, future studies should carefully consider and address the conceptual and methodological considerations outlined in this guidance paper. In highlighting these challenges, and providing specific recommendations for how to address them, our goal is to improve the quality of research carried out on this topic., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background and Aims: The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice., Methods: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting., Results and Conclusions: Results of our consensus process yielded five key evidence-based and feasibility barriers for the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols. To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity., Objectives: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias., Methods: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population-based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%-8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m 2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose-lowering medications within 180 days." To address disease latency, 1-year lag time was applied to the end of the 180-day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity-score weighted Cox proportional hazard models., Results: Over mean follow-up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person-years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96-1.15]), compared to delayed or no glucose-lowering medication initiation (N = 22,369; 1768 events; 117,415 person-years)., Conclusion: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Due to global climate change resulting in extreme temperature fluctuations, it becomes increasingly necessary to explore the natural genetic variation in model crops such as rice to facilitate the breeding of climate-resilient cultivars. To uncover genomic regions in rice involved in managing cold stress tolerance responses and to identify associated cold tolerance genes, two inbred line populations developed from crosses between cold-tolerant and cold-sensitive parents were used for quantitative trait locus (QTL) mapping of two traits: degree of membrane damage after 1 week of cold exposure quantified as percent electrolyte leakage (EL) and percent low-temperature seedling survivability (LTSS) after 1 week of recovery growth. This revealed four EL QTL and 12 LTSS QTL, all overlapping with larger QTL regions previously uncovered by genome-wide association study (GWAS) mapping approaches. Within the QTL regions, 25 cold-tolerant candidate genes were identified based on genomic differences between the cold-tolerant and cold-sensitive parents. Of those genes, 20% coded for receptor-like kinases potentially involved in signal transduction of cold tolerance responses; 16% coded for transcription factors or factors potentially involved in regulating cold tolerance response effector genes; and 64% coded for protein chaperons or enzymes potentially serving as cold tolerance effector proteins. Most of the 25 genes were cold temperature regulated and had deleterious nucleotide variants in the cold-sensitive parent, which might contribute to its cold-sensitive phenotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 At least a portion of this work is authored by AK Jackson, MH Jia, JD Edwards and GC Eizenga on behalf of the U.S. Government and as regards Mr. Jackson, Ms. Jia, Dr. Edwards and Dr. Eizenga and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.)

Objectives: Hospitalization in a PICU is a stressful experience for children and their parents, with many experiencing posttraumatic stress disorder (PTSD) after discharge. Risk factors may include preillness traumatic events, such as adverse childhood experiences (ACEs). We sought to assess the feasibility of screening ACEs in parents of children admitted to a PICU, their prevalence, and their association with post-PICU PTSD symptoms in them and their children., Design: Single-center prospective observational study., Setting: Urban academic children's hospital from January to December 2021., Patients: One hundred forty-five children (2-18 yr old, admitted ≥ 2 d) and their parents., Interventions: None., Measurements and Main Results: Data on parental demographics, ACEs, coping skills, and PICU environmental stressors, as well as patient clinical data, were collected. One month after PICU discharge, parents completed inventories assessing PTSD symptoms in them and their children. Bivariate and logistic regression analyses were used to explore associations of ACEs with post-PICU PTSD. Of 145 enrolled parents, 95% completed the ACE questionnaire, 58% of whom reported greater than or equal to 1 ACE, and 14% had substantial (≥ 4) ACEs. Parent and patient follow-up was 79% and 70%, respectively. Sixteen percent of parents had provisional PTSD. Regression analysis showed parents with greater than or equal to 4 ACEs had 10 times greater odds of parental PTSD, compared to parents with less than 4 ACEs, (adjusted odds ratio [aOR] = 10.2; 95% CI, 1.03-100.9; p = 0.047). Fifty-six percent of patients screened at risk for PTSD. There was no association between substantial parental ACEs and patients' risk for PTSD (aOR = 3.5 [95% CI, 0.56-21.31]; p = 0.18)., Conclusions: ACEs were common among parents of critically ill children. Having substantial parental ACEs was associated with provisional parental PTSD after their child's PICU admission, but not with PTSD in the children. Family-centered care that seeks to mitigate post-PICU stress should be mindful of the potential relevance of parental ACEs., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)