380 research outputs found

    Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older UK Biobank Participants

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    This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND/OBJECTIVES Delirium is common in older adults, especially following hospitalization. Because low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship. DESIGN Prospective cohort analysis. SETTING Community‚Äźbased cohort study of adults from 22 cities across the United Kingdom (the UK Biobank). PARTICIPANTS Adults aged 60 and older by the end of follow‚Äźup in the linked hospital inpatient admissions data, up to 14‚ÄČyears after baseline (n = 351,320). MEASUREMENTS At baseline, serum vitamin D (25‚ÄźOH‚ÄźD) levels were measured. We used time‚Äźto‚Äźevent models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D deficiency and incident hospital‚Äźdiagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk. RESULTS A total of 3,634 (1.03%) participants had at least one incident hospital‚Äźdiagnosed delirium episode. Vitamin D deficiency (50‚ÄČnmol/L). Increased risk was not limited to the deficient group: insufficient levels (25‚Äď50‚ÄČnmol/L) were also at increased risk (HR = 1.38; 95% CI = 1.28‚Äď1.49; P =‚ÄČ4*10‚ąí18). The association was independent of calcium levels, hospital‚Äźdiagnosed fractures, dementia, and other relevant cofactors. In genetic analysis, participants carrying more vitamin D‚Äďincreasing variants had a reduced likelihood of incident delirium diagnosis (HR = .80 per standard deviation increase in genetically instrumented vitamin D: .73‚Äď.87; P =‚ÄČ2*10‚ąí7). CONCLUSION Progressively lower vitamin D levels predicted increased risks of incident hospital‚Äźdiagnosed delirium, and genetic evidence supports a shared causal pathway. Because low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.Alzheimer‚Äôs SocietyMedical Research Council (MRC)National Institute on Agin

    Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study

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    Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (\u3c3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure

    National Eldercare System Project: A National Study Comparing Successful Community-based Systems of Care for Older People

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    The purpose of this project was to compare three different models of building and strengthening community-based systems of care for older adults. Models were distinguished by the type of organization that took the lead in developing the system of services: Area Agency on Aging, acute care hospital, and residential facility. Specific questions addressed in this project were: (1) What conditions in a local community give rise to a community-based system of care (CBSC) for older adults? (2) What are the necessary steps in planning and designing CBSCs? (3) How are successful CBSCs established and maintained? (4) How does the type of lead organization influence a CBSCs accessibility, responsiveness, and effectiveness? (5) To what extent and under what conditions can successful CBSCs be replicated? Answers to these questions were meant to assist leaders in new communities wishing to develop CBSCs for older adults in their own locales

    Case Report Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant

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    Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk

    Predicting incident delirium diagnoses using data from primary-care electronic health records

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    Importance risk factors for delirium in hospital inpatients are well established, but less is known about whether delirium occurring in the community or during an emergency admission to hospital care might be predicted from routine primary-care records. Objectives identify risk factors in primary-care electronic health records (PC-EHR) predictive of delirium occurring in the community or recorded in the initial episode in emergency hospitalisation. Test predictive performance against the cumulative frailty index. Design Stage 1: case-control; Stages 2 and 3: retrospective cohort. Setting clinical practice research datalink: PC-EHR linked to hospital discharge data from England. Subjects Stage 1: 17,286 patients with delirium aged ‚Č•60 years plus 85,607 controls. Stages 2 and 3: patients‚ÄČ‚Č•‚ÄČ60 years (n =‚ÄČ429,548 in 2015), split into calibration and validation groups. Methods Stage 1: logistic regression to identify associations of 110 candidate risk measures with delirium. Stage 2: calibrating risk factor weights. Stage 3: validation in independent sample using area under the curve (AUC) receiver operating characteristic. Results fifty-five risk factors were predictive, in domains including: cognitive impairment or mental illness, psychoactive drugs, frailty, infection, hyponatraemia and anticholinergic drugs. The derived model predicted 1-year incident delirium (AUC‚ÄČ=‚ÄČ0.867, 0.852:0.881) and mortality (AUC‚ÄČ=‚ÄČ0.846, 0.842:0.853), outperforming the frailty index (AUC‚ÄČ=‚ÄČ0.761, 0.740:0.782). Individuals with the highest 10% of predicted delirium risk accounted for 55% of incident delirium over 1 year. Conclusions a risk factor model for delirium using data in PC-EHR performed well, identifying individuals at risk of new onsets of delirium. This model has potential for supporting preventive interventions

    Mid-life Leukocyte Telomere Length and Dementia Risk: An Observational and Mendelian Randomization Study of 435,046 UK Biobank Participants

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    Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer\u27s disease and Alzheimer\u27s disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n =‚ÄČ435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2‚ÄČyears. In a subsample without AD/ADRD and with brain imaging data (n =‚ÄČ43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90‚Äď0.96, p =‚ÄČ3.37‚ÄČ√ó‚ÄČ10‚ąí7). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies

    Effects of Pharmacologically Induced Hypogonadism on Mood and Behavior in Healthy Young Women

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    The relationship between depression and estrogen withdrawal remains controversial. The authors examined the effects of gonadotropin-releasing hormone agonist-induced ovarian suppression on mood, sleep, sexual function, and nighttime hot flushes. They focused on whether participating women experienced clinically significant depressive symptoms and whether specific symptoms associated with hypogonadism (nighttime hot flushes and disturbed sleep) increased susceptibility to depression

    A Cross-Sectional Evaluation of Perimenopausal Depression

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    Overall, the clinical spectrum of depression during the perimenopause is not well characterized. This cross-sectional study examined the following: 1) clinical characteristics of women who presented to the NIMH midlife mood disorders clinic (between March 1990 and January 2004) with perimenopausal major and minor depressions; 2) the impact on these measures of either a prior episode of depression or the presence of hot flushes
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