Education and the moderating roles of age,sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

BackgroundWe examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).MethodsParticipants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.ResultsCompared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.ConclusionHigh School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.     

Early-adulthood caloric restriction is beneficial to improve renal redox status as future anti-aging strategy in rats

AimsCaloric restriction (CR) is an experimental approach proposed to alleviate age-related oxidative damage. In the present study, we investigated the consequences of CR on renal redox homeostasis in rats at a specific time frame in early-adulthood..MethodsThree groups of male Sprague-Dawley rats; young control at 6-month-old, 2-year-old subjected to 40% CR between 18^th-24^th months of age, and their non-CR controls were sacrificed, and numerous redox status biomarkers including protein oxidation, glycation, lipid peroxidation, glycation end products, thiol groups, and superoxide dismutase were assayed. It was also ensured that CR rats and their non-CR corresponding rats had similar body weights at the end of the study to decrease the confounding effects of different body weights on redox homeostasis and caloric restriction.ResultsAfter CR, the detrimental effects of the protein oxidation, glycation, and lipid peroxidation were significantly improved in the renal tissue CR rats when compared to their non-CR control group. However, there were no significant difference in thiol fractions between younger controls and both of the elderly groups.ConclusionDetrimental consequences of renal senescence on redox homeostasis are significantly improved via CR especially applied in early-adulthood.     

Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases

Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.     

School physical activity policies and associations with physical activity practices and behaviours: A systematic review of the literature

The development and implementation of school policies is considered a key strategy for the promotion of physical activity (PA) in children and adolescents. This study aimed to systematically review and synthesise existing literature focusing on the associations between formal written school-based PA policies and (a) school PA practices and (b) PA behaviours of school-aged children and adolescents. Fifty-one papers reporting on 52 studies met the eligibility criteria. All but two studies were from high income countries, most used cross-sectional designs and demonstrated fair methodological quality, and just over a third examined language aspects of policies. Findings predominantly indicated a lack of or inconclusive associations between the various characteristics examined and PA outcomes. Inconclusive associations were identified between both PA practice and behaviour outcomes and state level policies, policies focusing on PE and school-day PA, and in studies examining language aspects of policies. Inconclusive associations with both types of outcomes were more likely to be identified compared to a lack of associations in studies using self-report measures and in studies not providing information about the quality of exposure and outcome measures used. Overall, findings highlight the need for further research that acknowledges the complex relationship between school policies and PA outcomes and employs robust methodological approaches to enhance our understanding of this area.     

Anticholinergic drug exposure at intensive care unit admission affects the occurrence of delirium. A prospective cohort study

BackgroundAnticholinergic drugs may increase the risk of delirium in non-critically ill patients, but it is unclear whether exposure to these drugs is also a risk factor for Intensive Care Unit (ICU) delirium. In this study the hypothesis was tested that anticholinergic drug exposure at ICU admission increases the risk to develop delirium during ICU stay, particularly in patients with advanced age and severe sepsis.MethodsA prospective cohort study was performed in the mixed 32-bed medical-surgical ICU of the University Medical Center Utrecht, the Netherlands in the period from January 2011 till June 2013. Included were nonneurological patients that were consecutively admitted for more than 24 hours. The presence of delirium was evaluated each day using a validated algorithm based on the Confusion Assessment Method for the ICU (CAM-ICU), the initiation of delirium treatment as well as chart review by researchers. Anticholinergic drug exposure at ICU admission was assessed using the Anticholinergic Drug Scale (ADS). To evaluate the association between anticholinergic drug exposure at ICU admission and the risk of developing delirium, we performed multivariable competing risk Cox proportional hazard analysis corrected for confounding factors.ResultsApproximately half (47%, n=513) of the 1090 included patients developed delirium during ICU admission. The absolute risk for delirium development increased with more anticholinergic drug exposure: 42% in patients with ADS score=0, 49% in patients with ADS score=1, and 53% in patients with ADS higher than 1. Taking competing events (death and discharge) and potential confounding factors into account, the subdistribution hazard ratio (SHR) was 1.13 (95% CI: 0.91-1.40) for ADS score=1 point and 1.35 (95% CI: 1.09-1.68) for ADS ≥2 compared with an ADS score=0 (no anticholinergic drug exposure). The effect was strongest during the first days of ICU admittance and was strongest in patients above 65 year without severe sepsis and/or septic shock (SHR 2.15, 95% CI 1.43-3.25).ConclusionsAnticholinergic drug exposure at ICU admission increases the risk of delirium in critically ill patients. This effect was most pronounced in patients older than 65 years without severe sepsis and/or septic shock, and declining over time.     

Rationale and design of the Kidney Precision Medicine Project

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A novel methodology to measure waiting times for community-based specialist care in a public healthcare system

BackgroundMonitoring waiting time (WT) in healthcare systems is essential, since long WT are associated with adverse health outcomes, reduced patient satisfaction and increased private financing.ObjectiveTo describe a methodology developed for routine national monitoring of WT for community-based non-urgent specialist appointments, in a public healthcare system.MethodsThe methodology is based on data from computerized appointment scheduling systems of all Health Maintenance Organizations (HMOs) in Israel. Data included first 50 available appointments for community-based specialists and actual number of visits. Five most frequent specialties: orthopedics, ophthalmology, gynecology, dermatology and otolaryngology, were included.WT offered to HMO members for non-urgent care was calculated for two scenarios: "specific" physician and "any" physician in the region. Distribution of offered WT was calculated separately for each specialty and geographical region, combined to create the nationwide distribution.ResultsThe methodology was tested on data extracted between December 2018-June 2019. Estimated national median WT for "specific" physician, ranged from 9 days (ophthalmology/gynecology) to 20 days (dermatology), with large variation between geographic regions. WT were 26–56 % shorter for "any" than for "specific" physician.ConclusionsThis novel method offers a solution for ongoing national WT measurement, using computerized scheduling systems. It integrates two scenarios for appointment scheduling and allows identification of differences between specialties and regions, setting the ground for interventions to strengthen public healthcare systems.