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[This corrects the article DOI: 10.1371/journal.pone.0275642.].

Background The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear. Methods Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003–5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders. Results Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65–74, 75–79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y. Conclusions PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP.

BackgroundBacterial infections of the upper and lower respiratory tract are a frequent complication of influenza and contribute to the widespread use of antibiotics. Influenza vaccination may help reduce both appropriate and inappropriate prescribing of antibiotics. Electronic health records provide a rich source of information for assessing secondary effects of influenza vaccination.MethodsWe conducted a retrospective study to estimate effects of influenza vaccine on antibiotic (amoxicillin) prescription in the elderly based on data from the Clinical Practice Research Datalink. The introduction of UK policy to recommend the influenza vaccine to older adults in 2000 led to a substantial increase in uptake, creating a natural experiment. Of 259,753 eligible patients that were unvaccinated in 1999 and aged≥65y by January 2000, 88,519 patients received influenza vaccination in 2000. These were propensity score matched 1:1 to unvaccinated patients. Time-to-amoxicillin was analysed using the Prior Event Rate Ratio (PERR) Pairwise method to address bias from time-invariant measured and unmeasured confounders. A simulation study and negative control outcome were used to help strengthen the validity of results.ResultsCompared to unvaccinated patients, those from the vaccinated group were more likely to be prescribed amoxicillin in the year prior to vaccination: hazard ratio (HR) 1.90 (95% confidence interval 1.83, 1.98). Following vaccination, the vaccinated group were again more likely to be prescribed amoxicillin, HR 1.64 (1.58,1.71). After adjusting for prior differences between the two groups using PERR Pairwise, overall vaccine effectiveness was 0.86 (0.81, 0.92). Additional analyses suggested that provided data meet the PERR assumptions, these estimates were robust.ConclusionsOnce differences between groups were taken into account, influenza vaccine had a beneficial effect, lowering the frequency of amoxicillin prescribing in the vaccinated group. Ensuring successful implementation of national programmes of vaccinating older adults against influenza may help contribute to reducing antibiotic resistance.

Introduction To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).Research design and methods We assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation.Results Genital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; 5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07).Conclusions Female sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.

AIMS:Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c. METHODS:We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate 'pre-baseline' HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c. RESULTS:Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,p

Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (

Background: Shortfalls in the receipt of recommended health care have been previously reported in England, leading to preventable poor health. Objectives: To assess changes over 6 years in the receipt of effective health-care interventions for people aged 50 years or over in England with cardiovascular disease, depression, diabetes or osteoarthritis; to identify how quality varied with participant characteristics; and to compare the distribution of illness burden in the population with the distributions of diagnosis and treatment. Setting and participants: Information on health-care quality indicators and participant characteristics was collected using face-to-face structured interviews and nurse visits in participants’ homes by the English Longitudinal Study of Ageing in 2004–5, 2006–7, 2008–9 and 2010–11. A total of 16,773 participants aged 50 years or older were interviewed at least once and 5114 were interviewed in all four waves; 5404 reported diagnosis of one or more of four conditions in 2010–11. Main outcome measures: Percentage of indicated health care received by eligible participants for 19 quality indicators: seven for cardiovascular disease, three for depression, five for diabetes and four for osteoarthritis, and condition-level quality indicator achievement, including achievement of a bundle of three diabetes indicators. Analysis: Changes in quality indicator achievement over time and variations in quality with participant characteristics were tested with Pearson’s chi-squared test and logistic regression models. The size of inequality between the hypothetically wealthiest and poorest participants, for illness burden, diagnosis and treatment, was estimated using slope indices of wealth inequality. Results: Achievement of indicators for cardiovascular disease was 82.7% [95% confidence interval (CI) 79.9% to 85.5%] in 2004–5 and 84.2% (95% CI 82.1% to 86.2%) in 2010–11, for depression 63.3% (95% CI 57.6% to 69.0%) and 59.8% (95% CI 52.4% to 64.3%), for diabetes 76.0% (95% CI 74.1% to 77.8%) and 76.5% (95% CI 74.8% to 78.1%), and for osteoarthritis 31.2% (95% CI 28.5% to 33.8%) and 35.6% (95% CI 34.2% to 37.1%). Achievement of the diabetes care bundle was 67.8% (95% CI 64.5% to 70.9%) in 2010–11. Variations in quality by participant characteristics were generally small. Diabetes indicator achievement was worse in participants with cognitive impairment [odds ratio (OR) 0.5, 95% CI 0.4 to 0.7] and better in those living alone (OR 1.7, 95% CI 1.3 to 2.0). Hypertension care was better for those aged over 74 years (vs. 50–64 years) (OR 3.2, 95% CI 2.0 to 5.3). Osteoarthritis care was better for those with severe (vs. mild) pain (OR 1.8, 95% CI 1.4 to 2.2), limiting illness (OR 1.8, 95% CI 1.5 to 2.1), and obesity (OR 1.6, 95% CI 1.2 to 2.0). Previous non-achievement of the diabetes care bundle was the biggest predictor of non-achievement 2 years later (OR 3.3, 95% CI 2.2 to 4.7). Poorer participants were always more likely than wealthier participants to have illness burden (statistically significant OR 3.9 to 16.0), but not always more likely to be diagnosed or receive treatment (0.2 to 5.3). Conclusions: Shortfalls in quality of care for these four conditions have persisted over 6 years, with only half of the level of indicated health care achieved for osteoarthritis, compared with the other three conditions. Quality for osteoarthritis improved slightly over time but remains poor. The relatively high prevalence of specific illness burden in poorer participants was not matched by an equally high prevalence of diagnosis or treatment, suggesting that barriers to equity may exist at the stage at diagnosis. Further research is needed into the association between quality and health system characteristics at the level of clinicians, general practices or hospitals, and regions. Linkage to routinely collected data could provide information on health service characteristics at the individual patient level. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Schools are common sites for obesity prevention interventions. Although many theories suggest that the school context influences weight status, there has been little empirical research. The objective of this study was to explore whether features of the school context were consistently and meaningfully associated with pupil weight status (overweight or obese). Exploratory factor analysis of routinely collected data on 319 primary schools in Devon, England, was used to identify possible school-based contextual factors. Repeated cross-sectional multilevel analysis of five years (2006/07-2010/11) of data from the National Child Measurement Programme was then used to test for consistent and meaningful associations. Four school-based contextual factors were derived which ranked schools according to deprivation, location, resource and prioritisation of physical activity. None of which were meaningfully and consistently associated with pupil weight status, across the five years. The lack of consistent associations between the factors and pupil weight status suggests that the school context is not inherently obesogenic. In contrast, incorporating findings from education research indicates that schools may be equalising weight status, and obesity prevention research, policy and practice might need to address what is happening outside schools and particularly during the school holidays.

AIMS:Defining responders to glucose lowering therapy can be important for both clinical care and for the development of a stratified approach to diabetes management. Response is commonly defined by either HbA1c change after treatment or whether a target HbA1c is achieved. We aimed to determine the extent to which the individuals identified as responders and non-responders to glucose lowering therapy, and their characteristics, depend on the response definition chosen. METHODS:We prospectively studied 230 participants commencing GLP-1 agonist therapy. We assessed participant characteristics at baseline and repeated HbA1c after 3 months treatment. We defined responders (best quartile of response) based on HbA1c change or HbA1c achieved. We assessed the extent to which these methods identified the same individuals and how this affected the baseline characteristics associated with treatment response. RESULTS:Different definitions of response identified different participants. Only 39% of responders by one definition were also good responders by the other. Characteristics associated with good response depend on the response definition chosen: good response by HbA1c achieved was associated with low baseline HbA1c (p

Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses.To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n=86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD=5.96 ng/ml OR=1.43, CI 1.03 to 1.98, p=0.033), and near significant for intermediate disease (OR=1.69, CI 0.98 to 2.94, p=0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined.BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.

BackgroundBisphenol A (BPA) is a high production volume chemical widely used in food and drinks packaging. Associations have previously been reported between urinary BPA concentrations and heart disease, diabetes and liver enzymes in adult participants of the National Health and Nutrition Examination Survey (NHANES) 2003/04. We aimed to estimate associations between urinary BPA concentrations and health measures in NHANES 2005/06 and in data pooled across collection years.Methodology and findingsA cross-sectional analysis of NHANES: subjects were n = 1455 (2003/04) and n = 1493 (2005/06) adults aged 18-74 years, representative of the general adult population of the United States. Regression models were adjusted for age, sex, race/ethnicity, education, income, smoking, BMI, waist circumference, and urinary creatinine concentration. Main outcomes were reported diagnoses of heart attack, coronary heart disease, angina and diabetes and serum liver enzyme levels. Urinary BPA concentrations in 2005/06 (geometric mean 1.79 ng/ml, 95% CI: 1.64 to 1.96) were lower than in 2003/04 (2.49 ng/ml, CI: 2.20 to 2.83, difference p-value = 0.00002). Higher BPA concentrations were associated with coronary heart disease in 2005/06 (OR per z-score increase in BPA = 1.33, 95%CI: 1.01 to 1.75, p = 0.043) and in pooled data (OR = 1.42, CI: 1.17 to 1.72, p = 0.001). Associations with diabetes did not reach significance in 2005/06, but pooled estimates remained significant (OR = 1.24, CI: 1.10 to 1.40, p = 0.001). There was no overall association with gamma glutamyl transferase concentrations, but pooled associations with alkaline phosphatase and lactate dehydrogenase remained significant.ConclusionsHigher BPA exposure, reflected in higher urinary concentrations of BPA, is consistently associated with reported heart disease in the general adult population of the USA. Studies to clarify the mechanisms of these associations are urgently needed.