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Background: As the prevalence of childhood mental health conditions varies by age and gender, we explored whether there were similar variations in the relationship between psychopathology and exclusion from school in a prospective UK population‐based birth cohort. Method: The Avon Longitudinal Study of Parents and Children collected reports of exclusion at 8 years and 16 years. Mental health was assessed at repeated time points using the Strengths and Difficulties Questionnaire (SDQ). Results: Using adjusted linear mixed effects models, we detected a nonlinear interaction between exclusion and age related to poor mental health for boys [adjusted coefficient 1.13 (95% confidence interval 0.55–1.71)] excluded by age 8, but not for girls. The SDQ scores of boys who were excluded in primary school were higher than their peers from age 3, and increasingly diverged over time. As teenagers, these interactions appeared for both genders [boys' adjusted coefficient 0.18 (0.10–0.27); girls 0.29 (0.17–0.40)]. For teenage girls, exclusion by 16 was followed by deteriorating mental health. Family adversity predicted exclusion in all analyses. Conclusion: Prompt access to effective intervention for children in poor mental health may improve both mental health and access to education. Key Practitioner Message: Children who were subsequently excluded from school often faced family adversity and had poor mental health, which suggests the need for an interdisciplinary response and a multiagency approach.Poor mental health may contribute to and result from exclusion from school, so both mental health and education practitioners have a key role to play.Boys who enter school with poor mental health are at high risk of exclusion in primary school, which prompt assessment and intervention may prevent.Both boys and girls who are excluded between the ages of 15 and 16 years may have poor, and in the case of girls, deteriorating, mental health. [ABSTRACT FROM AUTHOR]

The prevalence of epileptic seizures is increased in patients in the clinical stages of Alzheimer's disease (AD) when compared to age-matched cognitively normal populations. In previously reported work from the Presentation of Epileptic Seizures in Dementia (PrESIDe) study, we identified a clinical suspicion of epilepsy in between 12.75 and 28.43% of patients with AD recruited from a memory clinic. EEGs were not performed in this study. Patients with epilepsy performed similarly to patients without epilepsy on cognitive testing at the time of recruitment but were more impaired on two measures of everyday functioning [Cambridge Behavioral Inventory—Revised and Clinical Dementia Rating (CBI-R and CDR)]. On repeated testing in this 12-month follow-up study, patients in whom a suspicion of epilepsy was identified performed significantly worse on cognitive function testing (p = 0.028) in addition to maintaining a difference on the informant questionnaires (CBI-R p < 0.001, CDR p = 0.020). These findings suggest that seizures in this population could be a marker of a more rapid decline and worse prognosis. [ABSTRACT FROM AUTHOR]

Background in chronic kidney disease (CKD), hypertension is associated with poor outcomes at ages <70 years. At older ages, this association is unclear. We tested 10-year mortality and cardiovascular outcomes by clinical systolic blood pressure (SBP) in older CKD Stages 3 and 4 patients without diabetes or proteinuria. Methods retrospective cohort in population representative primary care electronic medical records linked to hospital data from the UK. CKD staged by CKD-EPI equation (≥2 creatinine measurements ≥90 days apart). SBPs were 3-year medians before baseline, with mean follow-up 5.7 years. Cox competing models accounted for mortality. Results about 158,713 subjects with CKD3 and 6,611 with CKD4 met inclusion criteria. Mortality increased with increasing CKD stage in all subjects aged >60. In the 70 plus group with SBPs 140–169 mmHg, there was no increase in mortality, versus SBP 130–139. Similarly, SBPs 140–169 mmHg were not associated with increased incident heart failure, stroke or myocardial infarctions. SBPs <120 mmHg were associated with increased mortality and cardiovascular risk. At ages 60–69, there was increased mortality at SBP <120 and SBP >150 mmHg. Results were little altered after excluding those with declining SBPs during 5 years before baseline, or for longer-term outcomes (5–10 years after baseline). Conclusions in older primary care patients, CKD3 or 4 was the dominant outcome predictor. SBP 140–169 mmHg having little additional predictive value, <120 mmHg was associated with increased mortality. Prospective studies of representative older adults with CKD are required to establish optimum BP targets. [ABSTRACT FROM AUTHOR]

Objectives: To estimate associations between long‐term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. Design: Longitudinal analyses of electronic medical records. Setting: England Participants: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age‐ and sex‐matched controls (N=75,050). Measurements: Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. Results: During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR‐adjusted hazard ratio=1.82, 95% confidence interval=1.27–2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score– and inverse probability–weighted models. Conclusion: In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short‐term harms of PPIs should not divert attention from potential long‐term effects of PPI prescriptions on older adults. [ABSTRACT FROM AUTHOR]

Objective: A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy.Research Design and Methods: We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464).Results: In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P = 0.03], HOMA2 insulin resistance [P = 0.01], and triglycerides [P < 0.01]) were associated with reduced 6-month HbA1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1c response (both P < 0.01). A subgroup defined by obesity (BMI ≥30 kg/m2) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P < 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists.Conclusions: Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy. [ABSTRACT FROM AUTHOR]

Background: Moderate obesity in later life may improve survival, prompting calls to revise obesity control policies. However, this obesity paradox may be due to confounding from smoking, diseases causing weight-loss, plus varying follow-up periods. We aimed to estimate body mass index (BMI) associations with mortality, incident type 2 diabetes, and coronary heart disease in older people with and without the above confounders.Methods: Cohort analysis in Clinical Practice Research Datalink primary care, hospital and death certificate electronic medical records in England for ages 60 to more than 85 years. Models were adjusted for age, gender, alcohol use, smoking, calendar year, and socioeconomic status.Results: Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall death rates in all age groups. However, after excluding the specific confounders and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U-shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply rising risks above. In older age groups, mortality nadirs were at modestly higher BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity-1 at all ages and for coronary heart disease to age 84.Conclusions: Obesity is associated with shorter survival plus higher incidence of coronary heart disease and type 2 diabetes in older populations after accounting for the studied confounders, at least to age 84. These results cast doubt on calls to revise obesity control policies based on the claimed risk paradox at older ages. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on statin risk and effectiveness for patients aged 80+. We estimated risk of recurrent myocardial infarction, muscle-related and other adverse events, and statin-related incremental costs in "real-world" older patients treated with statins versus no statins.Methods: We used primary care electronic medical records from the UK Clinical Practice Research Datalink. Subhazard ratios (competing risk of death) for myocardial infarction recurrence (primary end point), falls, fractures, ischemic stroke, and dementia, and hazard ratios (Cox) for all-cause mortality were used to compare older (60+) statin users and 1:1 propensity-score-matched controls (n = 12,156). Participants were followed-up for 10 years.Results: Mean age was 76.5±9.2 years; 45.5% were women. Statins were associated with near significant reduction in myocardial infarction recurrence (subhazard ratio = 0.84, 0.69-1.02, p = .073), with protective effect in the 60-79 age group (0.73, 0.57-0.94) but a nonsignificant result in the 80+ group (1.06, 0.78-1.44; age interaction p = .094). No significant associations were found for stroke or dementia. Data suggest an increased risk of falls (1.36, 1.17-1.60) and fractures (1.33, 1.04-1.69) in the first 2 years of treatment, particularly in the 80+ group. Treatment was associated with lower all-cause mortality. Statin use was associated with health care cost savings in the 60-79 group but higher costs in the 80+ group.Conclusions: Estimates of statin effectiveness for the prevention of recurrent myocardial infarction in patients aged 60-79 years were similar to trial results, but more evidence is needed in the older group. There may be an excess of falls and fractures in very old patients, which deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown.Objective: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline.Methods: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively.Results: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34).Conclusions: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes. [ABSTRACT FROM AUTHOR]

Objectives To estimate the association between uric acid and cardiovascular mortality in older adults, independent of traditional risk factors, and to estimate the risk prediction gain by adding uric acid measurements to the Framingham Cardiovascular Risk Score ( FCRS). Design Longitudinal observational study of two population-based cohorts. Setting The Established Populations for Epidemiologic Studies of the Elderly, Iowa (Iowa- EPESE) and the Third National Health and Nutritional Examination Survey ( NHANES III). Participants One thousand twenty-eight Iowa- EPESE participants and 1,316 NHANES III participants. Selected participants were aged 70 and older without overt cardiovascular disease, renal dysfunction, or diuretic use who lived for 3 years or longer after baseline. Measurements Outcome was age at cardiovascular death during follow-up (12-20 years). Uric acid and cardiovascular risk factors such as smoking, systolic blood pressure, diabetes mellitus, obesity, serum cholesterol, and high-density lipoprotein cholesterol were measured at baseline. Results High serum uric acid (>7.0 mg/dL) was associated with male sex, obesity, lipid levels, and estimated glomerular filtration rate at baseline. Fully adjusted hazard ratios ( HRs) for cardiovascular death with high uric acid versus normal were 1.36 (95% confidence interval (CI) = 1.10-1.69) in Iowa-EPESE and 1.43 (95% CI = 1.04-1.99) in NHANES III; pooled HR was 1.38 (95% CI = 1.16-1.61). The net reclassification improvement achieved by adding uric acid measurement to the FCRS was 9% to 20%. Conclusion In individuals aged 70 and older without overt CVD, renal dysfunction, or diuretic use, serum uric acid greater than 7.0 mg/dL was associated with greater CVD mortality independent of classic CVD risk factors. Adding uric acid measurement to the FCRS would improve prediction in older adults. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 μg/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans. OBJECTIVE: We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans. METHODS: We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes. RESULTS: The geometric mean urinary BPA concentration was 3.65 ng/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 μg/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA > 4.6 ng/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0-2.4 ng/mL). CONCLUSIONS: Because activation of nuclear-receptor-mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults. [ABSTRACT FROM AUTHOR]

To identify predictors of extraordinary survival. Longitudinal study of a cohort of elderly people followed up until almost all have died. Two counties in Iowa; a part of the Established Populations for Epidemiologic Study of the Elderly. Two thousand eight hundred ninety community-dwelling citizens aged 65 to 85 at baseline and surviving at least 3 years. Data relating to age, sex, birth order, parental longevity, marital status, education, family income, social support, self-reported health, chronic diseases, blood pressure, body mass index, physical ability, exercise, life attitude and mental health were obtained. Extraordinary survivors (ESs) were defined to include approximately 10% of the longest survivors in their sex group. The 253 ESs were far more likely never to have smoked. In models adjusted for age, sex, and smoking, the earlier-life factors such as parental longevity, being earlier in the birth order (in women only), and body mass index at age 50 were associated with extraordinary survival. In similar models for predictors at age 65 to 85, extraordinary survival was associated with excellent self-reported health, fewer chronic diseases, better physical mobility and memory, and positive attitude toward life, but it was not associated with depression, anxiety, or sleep quality. In multivariable models, attitude toward life was not an independent predictor. Women in the top third of a cumulative score of independent predictors were 9.3 (95% confidence interval=4.4-19.6, P<.001) times as likely to reach extraordinary survival as those in the bottom third. ESs had fewer 'classical' risk factors and were in better health than their contemporaneous controls. Possibly genetic factors such as parental longevity and birth order appear to be less predictive in men than in women. [ABSTRACT FROM AUTHOR]

Background: facing the costs of population ageing, many governments aim to keep older people in employment for longer. Summary health measures predict early retirement, but more specific symptoms and conditions need to be identified to guide efforts to delay retirement.Objective: to identify common symptoms and conditions that predict early work exit, at the population level.Design: cohort study of community dwelling respondents to the English Longitudinal Study of Ageing.Setting and participants: a total of 1,693 workers aged 50 and over at baseline who were younger than the contemporaneous retirement age (60 for women, 65 for men) at 4-year follow-up.Results: a total of 308 (18.2%) individuals moved out of employment during the follow-up period. Advancing age, female gender, partner retirement, greater pension wealth, high alcohol consumption and fair or poor self-rated health were all associated with work exit. Accounting for these factors, reported difficulty walking a quarter mile was predictive of early work exit (odds ratio (OR) = 2.23; 95% confidence interval (CI) 1.42–3.52), especially where symptoms included lower limb pain and/or shortness of breath. Symptomatic depression (measured by Centre for Epidemiological Studies Depression scale) was also predictive of early work exit (OR = 1.52, CI 1.07, 2.18). About 50.8% of early retirees reported one or more of these specific health symptoms (depression, general pain, mobility limitations and leg pain when walking).Conclusion: older workers who report depressive symptoms or impaired physical mobility, especially with lower limb pain and shortness of breath, are at increased risk of early transition out of work. Health interventions targeting these conditions may enable older workers to remain in the labour force. [ABSTRACT FROM AUTHOR]

Depression is common in people who have experienced recent Acute Coronary Syndrome (ACS), and predicts worse medical outcomes. Mechanisms underpinning the development of depression and its association with poor medical outcomes are unclear however. The aim of this study was to investigate the role of perseverative negative thinking (e.g. worry and rumination) in predicting depression in people with recent ACS. Adults attending specialist inpatient and outpatient cardiology services who had recently experienced ACS were invited to participate in this observational prospective cohort study. Questionnaire assessments were completed within 6 months of index ACS (baseline), then 2 months and 6 months later. 169 participants (131 male (78%), median age 68 (±16) years) completed baseline questionnaires, and 111 completed follow-ups. After controlling for the effects of key covariates, baseline rumination was a significant predictor of depression at 6 months, accounting for 2% of the variance in depression. This association was partially mediated by poor problem-solving ability and lack of social support. Neither worry nor rumination at baseline were significant predictors of quality of life at 6 months. Rumination is a significant independent predictor of depression, and this association may be partially explained by deficits in problem-solving ability and reduced social support. Both rumination and problem solving may provide useful targets for the development of evidence-based interventions to reduce depression among people with coronary heart disease. [ABSTRACT FROM AUTHOR]

Introduction: Contemporary adolescents are deemed inactive, especially girls, but whether for biological reasons associated with their maturation, changes in their behavior or because of environmental constraints, is uncertain. We examined the trends in physical activity (PA) in relation to both biological and environmental factors in an attempt to establish what drives activity patterns from childhood through adolescence. Methods: Physical activity (7-d Actigraph accelerometry) was measured annually from 5 to 15 yr in a single cohort of some 300 UK children. Total PA (TPA; in-school and out-of-school separately and combined as whole day) and intensity-specific PA (sedentary, light, and moderate-and-vigorous [MVPA]) were analyzed. Biological age (years before/after measured peak height velocity) and pubertal stage (self-reported pubic hair development-Tanner staging) were also measured as was socioeconomic status (postcode-derived index of multiple deprivation [IMD]). Results: Total PA was stable from 5 to 8 yr (trend P = 0.10) but fell progressively from 9 to 15 yr (by approximately 30% in girls and approximately 20% in boys, both P < 0.001; sex interaction, P < 0.01). Half of this fall was attributable to light intensity PA and only a quarter to MVPA. The decline in PA was related similarly to chronological and biological age, whereas pubertal stage explained the more rapid PA decline in girls (puberty-adjusted sex interaction, P = 0.51). Total PA fell to the same extent for in-school and out-of-school settings (both P < 0.001), and for lower and higher IMD areas (both P < 0.001). Total PA tracked moderately to strongly from childhood into adolescence (r = 0.58; P G 0.001). Conclusions: The adolescent decline in PA is consistent across different environmental settings, attributable to falls in light-intensity/habitual activity and influenced by puberty, suggesting that the inactivity of adolescence may, in part, be under biological control [ABSTRACT FROM AUTHOR]