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Good data curation is integral to cohort studies, but it is not always done to a level necessary to ensure the longevity of the data a study holds. In this opinion paper, we introduce the concept of data curation debt-the data curation equivalent to the software engineering principle of technical debt. Using the context of UK cohort studies, we define data curation debt-describing examples and their potential impact. We highlight that accruing this debt can make it more difficult to use the data in the future. Additionally, the long-running nature of cohort studies means that interest is accrued on this debt and compounded over time-increasing the impact a debt could have on a study and its stakeholders. Primary causes of data curation debt are discussed across three categories: longevity of hardware, software and data formats; funding; and skills shortages. Based on cross-domain best practice, strategies to reduce the debt and preventive measures are proposed-with importance given to the recognition and transparent reporting of data curation debt. Describing the debt in this way, we encapsulate a multi-faceted issue in simple terms understandable by all cohort study stakeholders. Data curation debt is not only confined to the UK, but is an issue the international community must be aware of and address. This paper aims to stimulate a discussion between cohort studies and their stakeholders on how to address the issue of data curation debt. If data curation debt is left unchecked it could become impossible to use highly valued cohort study data, and ultimately represents an existential risk to studies themselves. [ABSTRACT FROM AUTHOR]

Background: In the UK, general practitioners (GPs) are the most commonly used providers of care for emotional concerns.Objective: To update and synthesize literature on barriers and facilitators to GP-patient communication about emotional concerns in UK primary care.Design: Systematic review and qualitative synthesis.Method: We conducted a systematic search on MEDLINE (OvidSP), PsycInfo and EMBASE, supplemented by citation chasing. Eligible papers focused on how GPs and adult patients in the UK communicated about emotional concerns. Results were synthesized using thematic analysis.Results: Across 30 studies involving 342 GPs and 720 patients, four themes relating to barriers were: (i) emotional concerns are difficult to disclose; (ii) tension between understanding emotional concerns as a medical condition or arising from social stressors; (iii) unspoken assumptions about agency resulting in too little or too much involvement in decisions and (iv) providing limited care driven by little time. Three facilitative themes were: (v) a human connection improves identification of emotional concerns and is therapeutic; (vi) exploring, explaining and negotiating a shared understanding or guiding patients towards new understandings and (vii) upfront information provision and involvement manages expectations about recovery and improves engagement in treatment.Conclusion: The findings suggest that treatment guidelines should acknowledge: the therapeutic value of a positive GP-patient relationship; that diagnosis is a two-way negotiated process rather than an activity strictly in the doctor's domain of expertise; and the value of exploring and shaping new understandings about patients' emotional concerns and their management. [ABSTRACT FROM AUTHOR]

This paper investigates possible spillover effects of the UK minimum wage. The halt in the growth in inequality in the lower half of the wage distribution (as measured by the 50:10 percentile ratio) since the mid-1990s, in contrast to the continued inequality growth in the upper half of the distribution, suggests the possibility of a minimum wage effect and spillover effects on wages above the minimum. This paper analyses individual wage changes, using both a difference-in-differences estimator and a specification involving comparisons across minimum wage upratings, and concludes that there have not been minimum wage spillovers. Since the UK minimum wage has always been below the 10th percentile, this lack of spillovers implies that minimum wage changes have not had an effect on the 50:10 percentile ratio measure of inequality in the lower half of the wage distribution. [ABSTRACT FROM AUTHOR]

Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008-2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use. [ABSTRACT FROM AUTHOR]

This paper assesses the impact of Britain's accession to the EEC on her imports of manufactures. It argues that account must be taken of the substitutability of imports for home production, and that price effects must be modelled consistently. It applies Deaton and Muellbauer's “Almost Ideal Demand System” to annual data on UK home sales and imports from ten sources. It identifies considerable trade creation, but little or no trade diversion. [ABSTRACT FROM AUTHOR]

Domestic hot water (DHW) in the UK accounts for ∼7.5% of all energy use. For manufacturers of heating and hot water appliances to be in a position to respond to patterns of demand a full understanding of the effect of user-defined DHW profiles, different DHW systems and heating technologies are essential. This paper presents the prediction of the temperature characteristics of drawn DHW using artificial neural networks (NNs). We demonstrate whether, based on one NN model, different hot water system temperature loads can be accurately predicted. Two NN models were constructed and examined on a total of three systems. Both models trained on their associated systems produced errors of <11%; however, both NN models, when presented with unseen systems, produced large single errors. NN model 2 gave the lowest error when compared with NN model 1. [ABSTRACT FROM AUTHOR]

Aims Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering. Methods and results Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03–1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36–2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance. Conclusions Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background The Early CDT®-Lung antibody blood test plus serial computed tomography scans for test-positives (TPGs) reduces late-stage lung cancer presentation. This study assessed the psychological outcomes of this approach. Methods Randomized controlled trial (n  = 12 208) comparing psychological outcomes 1–12 months post-recruitment in a subsample (n  = 1032) of TPG, test-negative (TNG) and control groups (CG). Results Compared to TNG, TPG had lower positive affect (difference between means (DBM), 3 months (3m: −1.49 (−2.65, − 0.33)), greater impact of worries (DBM 1m: 0.26 (0.05, 0.47); 3m: 0.28 (0.07, 0.50)), screening distress (DBM 1m: 3.59 (2.28, 4.90); 3m: 2.29 (0.97, 3.61); 6m: 1.94 (0.61, 3.27)), worry about tests (odds ratio (OR) 1m: 5.79 (2.66, 12.63) and more frequent lung cancer worry (OR 1m: 2.52 (1.31, 4.83); 3m: 2.43 (1.26, 4.68); 6m: 2.87 (1.48, 5.60)). Compared to CG, TPG had greater worry about tests (OR 1m: 3.40 (1.69, 6.84)). TNG had lower negative affect (log-transformed DBM 3m: −0.08 (−0.13, −0.02)), higher positive affect (DBM 1m: 1.52 (0.43, 2.61); 3m: 1.43 (0.33, 2.53); 6m: 1.27 (0.17, 2.37)), less impact of worries (DBM 3m: −0.27 (−0.48, −0.07)) and less-frequent lung cancer worry (OR 3m: 0.49 (0.26, 0.92)). Conclusions Negative psychological effects in TPG and positive effects in TNG were short-lived and most differences were small. [ABSTRACT FROM AUTHOR]

Background In Europe, more than 15 million people live with heart failure (HF). It imposes an enormous social, organizational and economic burden. As a reaction to impending impact on healthcare provision, different country-specific structures for HF-care have been established. The aim of this report is to provide an overview and compare the HF-care approaches of Germany, Ireland, the Netherlands and the UK, and to open the possibility of learning from each other's experience. Methods A mixed methods approach was implemented that included a literature analysis, interviews and questionnaires with HF-patients and caregivers, and expert interviews with representatives from healthcare, health service research and medical informatics. Results The models of HF-care in all countries analyzed are based on the European Society of Cardiology guidelines for diagnosis and treatment of HF. Even though the HF-models differed in design and implementation in practice, key challenges were similar: (i) unequal distribution of care between urban and rural areas, (ii) long waiting times, (iii) unequal access to and provision of healthcare services, (iv) information and communication gaps and (v) inadequate implementation and financing of digital applications. Conclusion Although promising approaches exist to structure and improve HF-care, across the four countries, implementation was reluctant to embrace novel methods. A lack of financial resources and insufficient digitalization making it difficult to adopt new concepts. Integration of HF-nurses seems to be an effective way of improving current models of HF-care. Digital solutions offer further opportunities to overcome communication and coordination gaps and to strengthen self-management skills. [ABSTRACT FROM AUTHOR]

Background Public Health England has concluded that e-cigarettes are much safer than cigarettes for the user and for secondhand exposures, but it has not reached a definitive conclusion regarding pregnancy risks. How people perceive the risks to others is less well understood. Methods This study uses an online UK sample of 1041 adults to examine perceived e-cigarette risks to others and during pregnancy. The survey examines relative risk beliefs of e-cigarettes compared to cigarettes and the percentage reduction in harm provided by e-cigarettes. Results A majority of the sample believes that secondhand exposure to e-cigarette vapors poses less risk than secondhand smoke from cigarettes, but almost two-fifths of the sample equate the secondhand risks from e-cigarettes to those from cigarettes. There is somewhat greater perception of e-cigarette risks during pregnancy compared to beliefs regarding secondhand risks of vaping. About two-fifths of the population believe that e-cigarettes are less risky than cigarettes during pregnancy. Respondents believe that e-cigarettes reduce the harm to others by 39% and the harm to babies by 36%. Conclusion There is a general sense that e-cigarettes pose less risk than cigarettes, but there is a need for further risk communication regarding comparative e-cigarette risks. [ABSTRACT FROM AUTHOR]

Objective To establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) compared with a propensity-matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK. Methods This is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a predesigned standardized case record form. Adult patients (≥18 years) admitted between 1 April 2020 and 31 July 2020 were included. Results Overall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with SLE, RA or aPL syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia [240 (60.91%) vs 206 (52.28%), P  = 0.015], elevated LDH [150 (38.08%) vs 43 (10.92%), P  < 0.001] and raised creatinine [122 (30.96%) vs 86 (21.83%), P  = 0.01], respectively. A significantly higher proportion of patients with severe rheumatologic AD had elevated CRP [77 (96.25%) vs 70 (87.5%), P  = 0.044] and LDH [20 (25%) vs 6 (7.5%), P  = 0.021]. Patients with severe rheumatologic AD had significantly higher mortality [32/80 (40%)] compared with propensity matched cohort of patients without AD [20/80 (25%), P  = 0.043]. However, there was no difference in 180-day mortality between propensity-matched cohorts of patients with or without AD in general (P  = 0.47). Conclusions Patients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and elevated LDH were more frequent in patients with any AD while elevated CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n  = 1,141; C statistic: C  = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission. [ABSTRACT FROM AUTHOR]

Background Measurement of UK food insecurity has historically been inconsistent, making it difficult to understand trends. This study contributes by reporting and analysing data from a national survey conducted in line with UN Food and Agriculture Organization (FAO) recommendations and standard methods, providing an internationally comparable pre-coronavirus disease 2019 (COVID-19) snapshot of food insecurity. Methods Data came from a nationally representative 2019 UK sample (N  = 2000) surveyed by Ipsos-Mori. Prevalence of food insecurity was assessed using the UN FAO Food Insecurity Experience Scale. Logistic regression was used to model food insecurity in relation to geographic and socio-demographic variables. Results Severe food insecurity was reported by 3% of the sample, an increase of 66.7% over the last directly comparable UK analysis (Gallup World Poll data from 2016 to 2018). Indication of some degree of food insecurity was reported by 14.2% of the sample and tended to be higher amongst younger age groups, those on lower incomes, and home renters (as opposed to owners). No geographic variables were significantly associated with food insecurity prevalence. Conclusions The finding that prevalence of severe food insecurity was already increasing before the COVID-19 pandemic, across all areas of the UK, is cause for concern. Our results provide an important benchmark for assessing the impact of COVID-19 on food insecurity. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper presents the results from the first wide and deep dual narrow-band survey to select Hα and [O ii] line emitters at z= 1.47 ± 0.02, exploiting synergies between the United Kingdom Infrared Telescope and the Subaru telescope by using matched narrow-band filters in the H and z′ bands. The Hα survey at z= 1.47 reaches a 3σ flux limit of FHα≈ 7 × 10−17 erg s−1 cm−2 (corresponding to a limiting star formation rate (SFR) in Hα of ≈7 M⊙ yr−1) and detects ≈200 Hα emitters over 0.7 deg2, while the much deeper [O ii] survey reaches an effective flux of ≈7 × 10−18 erg s−1 cm−2 (SFR in [O ii] of ∼1 M⊙ yr−1), detecting ≈1400 z= 1.47 [O ii] emitters in a matched comoving volume of ∼2.5 × 105 Mpc3. The combined survey results in the identification of 190 simultaneous Hα and [O ii] emitters at z= 1.47. Hα and [O ii] luminosity functions are derived and both are shown to evolve significantly from z∼ 0 in a consistent way. The SFR density of the Universe at z= 1.47 is evaluated, with the Hα analysis yielding ρSFR= 0.16 ± 0.05 M⊙ yr−1 Mpc−3 and the [O ii] analysis ρSFR= 0.17 ± 0.04 M⊙ yr−1 Mpc−3. The measurements are combined with other studies, providing a self-consistent measurement of the star formation history of the Universe over the last ∼11 Gyr. By using a large comparison sample at z∼ 0.1, derived from the Sloan Digital Sky Survey (SDSS), [O ii]/Hα line ratios are calibrated as probes of dust extinction. Hα emitters at z∼ 1.47 show on average AHα≈ 1 mag, the same as found by SDSS in the local Universe. It is shown that although dust extinction correlates with SFR, the relation evolves by about ∼0.5 mag from z∼ 1.5 to ∼0, with local relations overpredicting the dust extinction corrections at high z by that amount. Stellar mass is found to be a much more fundamental extinction predictor, with the same relation between mass and dust extinction being valid at both z∼ 0 and ∼1.5, at least for low and moderate stellar masses. The evolution in the extinction-SFR relation is therefore interpreted as being due to the evolution in median specific SFRs over cosmic time. Dust extinction corrections as a function of optical colours are also derived and shown to be broadly valid at both z∼ 0 and ∼1.5, offering simpler mechanisms for estimating extinction in moderately star-forming systems over the last ∼9 Gyr. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper presents the results from the first wide and deep dual narrow-band survey to select Hα and [O ii] line emitters at z= 1.47 ± 0.02, exploiting synergies between the United Kingdom Infrared Telescope and the Subaru telescope by using matched narrow-band filters in the H and z′ bands. The Hα survey at z= 1.47 reaches a 3σ flux limit of FHα≈ 7 × 10−17 erg s−1 cm−2 (corresponding to a limiting star formation rate (SFR) in Hα of ≈7 M⊙ yr−1) and detects ≈200 Hα emitters over 0.7 deg2, while the much deeper [O ii] survey reaches an effective flux of ≈7 × 10−18 erg s−1 cm−2 (SFR in [O ii] of ∼1 M⊙ yr−1), detecting ≈1400 z= 1.47 [O ii] emitters in a matched comoving volume of ∼2.5 × 105 Mpc3. The combined survey results in the identification of 190 simultaneous Hα and [O ii] emitters at z= 1.47. Hα and [O ii] luminosity functions are derived and both are shown to evolve significantly from z∼ 0 in a consistent way. The SFR density of the Universe at z= 1.47 is evaluated, with the Hα analysis yielding ρSFR= 0.16 ± 0.05 M⊙ yr−1 Mpc−3 and the [O ii] analysis ρSFR= 0.17 ± 0.04 M⊙ yr−1 Mpc−3. The measurements are combined with other studies, providing a self-consistent measurement of the star formation history of the Universe over the last ∼11 Gyr. By using a large comparison sample at z∼ 0.1, derived from the Sloan Digital Sky Survey (SDSS), [O ii]/Hα line ratios are calibrated as probes of dust extinction. Hα emitters at z∼ 1.47 show on average AHα≈ 1 mag, the same as found by SDSS in the local Universe. It is shown that although dust extinction correlates with SFR, the relation evolves by about ∼0.5 mag from z∼ 1.5 to ∼0, with local relations overpredicting the dust extinction corrections at high z by that amount. Stellar mass is found to be a much more fundamental extinction predictor, with the same relation between mass and dust extinction being valid at both z∼ 0 and ∼1.5, at least for low and moderate stellar masses. The evolution in the extinction-SFR relation is therefore interpreted as being due to the evolution in median specific SFRs over cosmic time. Dust extinction corrections as a function of optical colours are also derived and shown to be broadly valid at both z∼ 0 and ∼1.5, offering simpler mechanisms for estimating extinction in moderately star-forming systems over the last ∼9 Gyr. [ABSTRACT FROM AUTHOR]

Background: With genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are available to address pleiotropy, but these assume independence between the gene-exposure and gene-outcome association estimates. Unlike in two-sample MR, in one-sample MR the two estimates are obtained from the same individuals, and the assumption of independence does not hold in the presence of confounding.Methods: With simulations mimicking a typical study in UK Biobank, we assessed the performance, in terms of bias and precision of the MR estimate, of the fixed-effect and (multiplicative) random-effects meta-analysis method, weighted median estimator, weighted mode estimator and MR-Egger regression, used in both one-sample and two-sample data. We considered scenarios differing by the: presence/absence of a true causal effect; amount of confounding; and presence and type of pleiotropy (none, balanced or directional).Results: Even in the presence of substantial correlation due to confounding, all two-sample methods used in one-sample MR performed similarly to when used in two-sample MR, except for MR-Egger which resulted in bias reflecting direction and magnitude of the confounding. Such bias was much reduced in the presence of very high variability in instrument strength across variants (IGX2 of 97%).Conclusions: Two-sample MR methods can be safely used for one-sample MR performed within large biobanks, expect for MR-Egger. MR-Egger is not recommended for one-sample MR unless the correlation between the gene-exposure and gene-outcome estimates due to confounding can be kept low, or the variability in instrument strength is very high. [ABSTRACT FROM AUTHOR]

Background: Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables.Methods: We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR.Results: In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index.Conclusions: Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution. [ABSTRACT FROM AUTHOR]

Background The coronavirus disease 2019 (COVID-19) pandemic may have a greater impact on people with disabilities than non-disabled people. Our aim was to compare the short-term impact of the 2020 COVID-19 pandemic and first lockdown on the employment and financial security of working age adults with and without disabilities in the UK. Methods Secondary analysis of data collected in Wave 9 and the special April, May and June COVID-19 monthly surveys of 'Understanding Society', the UK's main annual household panel study. Results During the first 3 months of the introduction of the COVID-19 lockdown in the UK, respondents with disability were more likely than their peers to be working reduced hours and experience higher levels of financial stress. These differences were attenuated, but not eliminated, when estimates were adjusted to take account of pre-lockdown financial status. Conclusions Working age adults with disability were particularly disadvantaged by the financial impact of the COVID-19 lockdown in the UK. The UN Secretary-General António Guterres has stated the need for a disability-inclusive COVID-19 government response. The results of our analysis suggest that these pleas have either not been heeded, or if measures have been implemented, they have so far been ineffectual in the UK. [ABSTRACT FROM AUTHOR]

Objectives Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP. Methods CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterized using 16S rRNA amplicon sequencing and amplicon sequence variants, and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors. Results Alpha diversity was significantly lower in CWP cases than controls (Mann–Whitney test, P -values 2.3e-04 and 1.2e-02, for Shannon and Simpson indices respectively). The species Coprococcus comes was significantly depleted in CWP cases (P adj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n  = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, P  = 7.4e-8). A Mendelian randomization study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP. Conclusions We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Study Question: Does the expansion of genome-wide association studies (GWAS) to a broader range of ancestries improve the ability to identify and generalise variants associated with age at menarche (AAM) in European populations to a wider range of world populations?Summary Answer: By including women with diverse and predominantly non-European ancestry in a large-scale meta-analysis of AAM with half of the women being of African ancestry, we identified a new locus associated with AAM in African-ancestry participants, and generalised loci from GWAS of European ancestry individuals.What Is Known Already: AAM is a highly polygenic puberty trait associated with various diseases later in life. Both AAM and diseases associated with puberty timing vary by race or ethnicity. The majority of GWAS of AAM have been performed in European ancestry women.Study Design, Size, Duration: We analysed a total of 38 546 women who did not have predominantly European ancestry backgrounds: 25 149 women from seven studies from the ReproGen Consortium and 13 397 women from the UK Biobank. In addition, we used an independent sample of 5148 African-ancestry women from the Southern Community Cohort Study (SCCS) for replication.Participants/materials, Setting, Methods: Each AAM GWAS was performed by study and ancestry or ethnic group using linear regression models adjusted for birth year and study-specific covariates. ReproGen and UK Biobank results were meta-analysed using an inverse variance-weighted average method. A trans-ethnic meta-analysis was also carried out to assess heterogeneity due to different ancestry.Main Results and the Role Of Chance: We observed consistent direction and effect sizes between our meta-analysis and the largest GWAS conducted in European or Asian ancestry women. We validated four AAM loci (1p31, 6q16, 6q22 and 9q31) with common genetic variants at P < 5 × 10-7. We detected one new association (10p15) at P < 5 × 10-8 with a low-frequency genetic variant lying in AKR1C4, which was replicated in an independent sample. This gene belongs to a family of enzymes that regulate the metabolism of steroid hormones and have been implicated in the pathophysiology of uterine diseases. The genetic variant in the new locus is more frequent in African-ancestry participants, and has a very low frequency in Asian or European-ancestry individuals.Large Scale Data: N/A.Limitations, Reasons For Caution: Extreme AAM (<9 years or >18 years) were excluded from analysis. Women may not fully recall their AAM as most of the studies were conducted many years later. Further studies in women with diverse and predominantly non-European ancestry are needed to confirm and extend these findings, but the availability of such replication samples is limited.Wider Implications Of the Findings: Expanding association studies to a broader range of ancestries or ethnicities may improve the identification of new genetic variants associated with complex diseases or traits and the generalisation of variants from European-ancestry studies to a wider range of world populations.Study Funding/competing Interest(s): Funding was provided by CHARGE Consortium grant R01HL105756-07: Gene Discovery For CVD and Aging Phenotypes and by the NIH grant U24AG051129 awarded by the National Institute on Aging (NIA). The authors have no conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Background: GPs are encouraged to make brief interventions to support weight loss, but they report concern about these conversations, stating that they need more details on what to say. Knowing how engage in these conversations could encourage GPs to deliver brief interventions for weight loss more frequently.Objective: To examine which specific words and phrases were successful in achieving conversational alignment and minimizing misunderstanding, contributing to effective interventions.Methods: A conversation analysis of English family practice patients participating in a trial of opportunistic weight-management interventions, which incorporated the offer of referral to community weight-management services (CWMS). Qualitative conversation analysis was applied to 246 consultation recordings to identify communication patterns, which contributed to clear, efficient interventions.Results: Analysis showed variation in how GPs delivered interventions. Some ways of talking created misunderstandings or misalignment, while others avoided these. There were five components of clear and efficient opportunistic weight-management referrals. These were (i) exemplifying CWMS with a recognizable brand name (ii) saying weight-management 'programme' or 'service', rather than 'group' or 'club' (iii) stating that the referral is 'free' early on (iv) saying the number CWMS visits available on referral (v) stating that the CWMS programme available was 'local'.Conclusions: When making a brief opportunistic intervention to support weight loss, clinicians can follow these five steps to create a smooth and efficient intervention. Knowing this may allay clinicians' fears about these consultations being awkward and improve adherence to guidelines. [ABSTRACT FROM AUTHOR]

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear.Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies.Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities. [ABSTRACT FROM AUTHOR]

Objectives OA is the most common form of arthritis worldwide and has a major impact on the quality of life among the older population. This study aimed at determining the potential causal effects of several serum nutritional factors on OA. Methods A total of seven serum nutritional factors were identified from genome-wide association studies. Summary statistics for OA were obtained from UK Biobank (194 153 for women and 166 988 for men) and a large genome-wide association studies meta-analysis based on the European population (455 221, 393 873 and 403 124 for overall, hip and knee OA, respectively). Two-sample Mendelian randomization approach was used to estimate the causal association between the selected nutritional factors and the risk of OA. Results The Mendelian randomization analyses suggested that serum calcium levels were inversely associated with overall OA (95% CI, 0.595, 0.850), hip OA (95% CI, 0.352, 0.799) and knee OA (95% CI, 0.461, 0.901). Serum retinol levels were also inversely associated with hip OA (95% CI, 0.257, 0.778). Moreover, sex-specific associations were observed between serum calcium levels (95% CI, 0.936, 0.998), iron levels (95% CI, 1.000, 1.012), selenium levels (95% CI, 0.923, 0.999) and OA in women. Conclusion In this study, an inverse causal association between serum calcium levels and OA was established. Serum retinol levels were inversely associated with hip OA. In addition, we provide evidence for the causal effect of serum calcium, iron and selenium on the risk of OA in women. [ABSTRACT FROM AUTHOR]

Objectives We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice. Methods We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group. Results The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9–3.4) times more likely to be in the shielding group than people with no previous LN (P  < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P  < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3–2.8) and Asian 1.9 (1.3–2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN. Conclusion Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding. [ABSTRACT FROM AUTHOR]

Objective: We assess the existence of unfair inequalities in health and death using the normative framework of inequality of opportunities, from birth to middle age in Great Britain.Methods: We use data from the 1958 National Child Development Study, which provides a unique opportunity to observe individual health from birth to the age of 54, including the occurrence of mortality. We measure health status combining self-assessed health and mortality. We compare and statistically test the differences between the cumulative distribution functions of health status at each age according to one childhood circumstance beyond people's control: the father's occupation.Results: At all ages, individuals born to a 'professional', 'senior manager or technician' father report a better health status and have a lower mortality rate than individuals born to 'skilled', 'partly skilled' or 'unskilled' manual workers and individuals without a father at birth. The gap in the probability to report good health between individuals born into high social backgrounds compared with low, increases from 12 percentage points at age 23 to 26 at age 54. Health gaps are even more marked in health states at the bottom of the health distribution when mortality is combined with self-assessed health.Conclusions: There is increasing inequality of opportunities in health over the lifespan in Great Britain. The tag of social background intensifies as individuals get older. Finally, there is added analytical value to combining mortality with self-assessed health when measuring health inequalities. [ABSTRACT FROM AUTHOR]

Background: We aimed to estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy makers and decision makers allocate resources efficiently and effectively.Methods: We used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors [alcohol intake, body mass index (BMI), cholesterol, systolic blood pressure, smoking] on 19 social and socioeconomic outcomes in 336 997 men and women of White British ancestry in UK Biobank, aged between 39 and 72 years. Outcomes included annual household income, employment, deprivation [measured by the Townsend deprivation index (TDI)], degree-level education, happiness, loneliness and 13 other social and socioeconomic outcomes.Results: Results suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income [mean difference = -£22 838, 95% confidence interval (CI): -£31 354 to -£14 321] and the chance of owning accommodation [absolute percentage change (APC) = -20.8%, 95% CI: -28.2% to -13.4%], of being satisfied with health (APC = -35.4%, 95% CI: -51.2% to -19.5%) and of obtaining a university degree (APC = -65.9%, 95% CI: -81.4% to -50.4%), while also increasing deprivation (mean difference in TDI = 1.73, 95% CI: 1.02 to 2.44, approximately 216% of a decile of TDI). There was evidence that asthma decreased household income, the chance of obtaining a university degree and the chance of cohabiting, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null.Conclusions: Higher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects. [ABSTRACT FROM AUTHOR]

Background We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. Methods We studied 4510 UK Biobank participants tested for COVID-19 (positive, n  = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. Results There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. Conclusions In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised. [ABSTRACT FROM AUTHOR]

Background: Little is known about population levels of energy expenditure, as national surveillance systems typically employ only crude measures. The National Diet and Nutrition Survey (NDNS) in the UK measured energy expenditure in a 10% subsample by gold-standard doubly labelled water (DLW).Methods: DLW-subsample participants from the NDNS (383 males, 387 females) aged 4-91 years were recruited between 2008 and 2015 (rolling programme). Height and weight were measured and body-fat percentage estimated by deuterium dilution.Results: Absolute total energy expenditure (TEE) increased steadily throughout childhood, ranging from 6.2 and 7.2 MJ/day in 4- to 7-year-olds to 9.7 and 11.7 MJ/day for 14- to 16-year-old girls and boys, respectively. TEE peaked in 17- to 27-year-old women (10.7 MJ/day) and 28- to 43-year-old men (14.4 MJ/day), before decreasing gradually in old age. Physical-activity energy expenditure (PAEE) declined steadily with age from childhood (87 kJ/day/kg in 4- to 7-year-olds) through to old age (38 kJ/day/kg in 71- to 91-year-olds). No differences were observed by time, region and macronutrient composition. Body-fat percentage was strongly inversely associated with PAEE throughout life, irrespective of expressing PAEE relative to body mass or fat-free mass. Compared with females with <30% body fat, females with >40% recorded 29 kJ/day/kg body mass and 18 kJ/day/kg fat-free mass less PAEE in analyses adjusted for age, geographical region and time of assessment. Similarly, compared with males with <25% body fat, males with >35% recorded 26 kJ/day/kg body mass and 10 kJ/day/kg fat-free mass less PAEE.Conclusions: This first nationally representative study reports levels of human-energy expenditure as measured by gold-standard methodology; values may serve as a reference for other population studies. Age, sex and body composition are the main determinants of energy expenditure. Key Messages This is the first nationally representative study of human energy expenditure, covering the UK in the period 2008-2015. Total energy expenditure (MJ/day) increases steadily with age throughout childhood and adolescence, peaks in the 3rd decade of life in women and 4th decade of life in men, before decreasing gradually in old age. Physical activity energy expenditure (kJ/day/kg or kJ/day/kg fat-free mass) declines steadily with age from childhood to old age, more steeply so in males. Body-fat percentage is strongly inversely associated with physical activity energy expenditure. We found little evidence that energy expenditure varied by geographical region, over time, or by dietary macronutrient composition. [ABSTRACT FROM AUTHOR]

Study Question: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally?Summary Answer: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age.What Is Known Already: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window.Study Design, Size, Duration: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis.Participants/materials, Setting, Methods: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models.Main Results and the Role Of Chance: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31-6.43, P =  0.009) and as quartiles (phet =  0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P =  0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured.Limitations, Reasons For Caution: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity.Wider Implications Of the Findings: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made.Study Funding/competing Interest(s): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Background: Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s.Methods: We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40-69 years at recruitment (2006-10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time.Results: During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4-37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2-24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4-12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk.Conclusions: Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (≤90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk. [ABSTRACT FROM AUTHOR]

We compute and compare risk-adjusted CEO pay in the United States and United Kingdom, where the risk adjustment is based on estimated risk premiums stemming from the equity incentives borne by CEOs. Controlling for firm and industry characteristics, we find that U.S. CEOs have higher pay, but also bear much higher stock and option incentives than U.K. CEOs. Using reasonable estimates of risk premiums, we find that risk-adjusted U.S. CEO pay does not appear to be large compared to that of U.K. CEOs. We also examine differences in pay and equity incentives between a sample of non-U.K. European CEOs and a matched sample of U.S. CEOs, and find that risk-adjusting pay may explain about half of the apparent higher pay for U.S. CEOs. [ABSTRACT FROM PUBLISHER]

Background: Short and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.Methods: We conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N = 395 803) and summary statistics from the International Genomics of Alzheimer's Project (N cases/controls = 17 008/37 154) to investigate the potential impact of sleep duration on cognitive outcomes.Results: Linear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI) = 0-2%; P = 0.008] slower reaction time and 3% more errors in visual-memory test (95% CI = 0-6%; P = 0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep = 1.10 (95% CI = 0.76-1.57); P = 0.62], decline in reaction time [OR = 1.28 (95% CI = 0.49-3.35); P = 0.61], all-cause dementia [OR = 1.19 (95% CI = 0.65-2.19); P = 0.57] or Alzheimer's disease risk [OR = 0.89 (95% CI = 0.67-1.18); P = 0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity = 3.44e-9) and reaction time (P for non-linearity = 6.66e-16).Conclusions: Linear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition. [ABSTRACT FROM AUTHOR]

Background: Mendelian randomization (MR) is a powerful tool in epidemiology that can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilizing genetic variants that are instrumental variables (IVs) for the exposure. This has been extended to multivariable MR (MVMR) to estimate the effect of two or more exposures on an outcome.Methods and Results: We use simulations and theory to clarify the interpretation of estimated effects in a MVMR analysis under a range of underlying scenarios, where a secondary exposure acts variously as a confounder, a mediator, a pleiotropic pathway and a collider. We then describe how instrument strength and validity can be assessed for an MVMR analysis in the single-sample setting, and develop tests to assess these assumptions in the popular two-sample summary data setting. We illustrate our methods using data from UK Biobank to estimate the effect of education and cognitive ability on body mass index.Conclusion: MVMR analysis consistently estimates the direct causal effect of an exposure, or exposures, of interest and provides a powerful tool for determining causal effects in a wide range of scenarios with either individual- or summary-level data. [ABSTRACT FROM AUTHOR]

Background: Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women.Methods: We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to 'uncouple' the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways.Results: Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P < 0.05. Using a metabolically favourable adiposity genetic risk score, and meta-analysing data from the UK biobank and PGC, a genetically determined 1 SD higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals (OR: 1.26, 95% CI: 1.06, 1.50], P = 0.010), but with weaker statistical confidence.Conclusions: Higher BMI, with and without its adverse metabolic consequences, is likely to have a causal role in determining the likelihood of an individual developing depression. [ABSTRACT FROM AUTHOR]

Background: Mendelian randomization (MR) has developed into an established method for strengthening causal inference and estimating causal effects, largely due to the proliferation of genome-wide association studies. However, genetic instruments remain controversial, as horizontal pleiotropic effects can introduce bias into causal estimates. Recent work has highlighted the potential of gene-environment interactions in detecting and correcting for pleiotropic bias in MR analyses.Methods: We introduce MR using Gene-by-Environment interactions (MRGxE) as a framework capable of identifying and correcting for pleiotropic bias. If an instrument-covariate interaction induces variation in the association between a genetic instrument and exposure, it is possible to identify and correct for pleiotropic effects. The interpretation of MRGxE is similar to conventional summary MR approaches, with a particular advantage of MRGxE being the ability to assess the validity of an individual instrument.Results: We investigate the effect of adiposity, measured using body mass index (BMI), upon systolic blood pressure (SBP) using data from the UK Biobank and a single weighted allelic score informed by data from the GIANT consortium. We find MRGxE produces findings in agreement with two-sample summary MR approaches. Further, we perform simulations highlighting the utility of the approach even when the MRGxE assumptions are violated.Conclusions: By utilizing instrument-covariate interactions in MR analyses implemented within a linear-regression framework, it is possible to identify and correct for horizontal pleiotropic bias, provided the average magnitude of pleiotropy is constant across interaction-covariate subgroups. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) has recently emerged as a salient global issue, and policy formulation to address AMR has become a contested space, with various actors sharing competing-and sometimes contradictory-explanations of the problem and the range of possible solutions. To facilitate national policy setting and implementation around AMR, more needs to be done to effectively engage policymakers in low- and middle-income countries (LMICs). However, there is a dearth of research on differences in issue framing by external agencies and LMIC's national policymakers on the problem of AMR; such analyses are imperative to identify areas of conflict and/or potential convergence. We compared representations of AMR across nine policy documents produced by multilateral agencies, donor countries and an LMIC at the forefront of the global response to AMR-Pakistan. We analysed the texts in relation to five narratives that have been commonly used to frame health issues as requiring action: economic impact, stunting of human development, consequences for health equity, health security threats and relationship with food production. We found that AMR was most frequently framed as a threat to human health security and economic progress, with several US, UK and international documents depicting LMICs as 'hotspots' for AMR. Human development and equity dimensions of the problem were less frequently discussed as reasons to address the growing burden of AMR. It is clear that no single coherent narrative on AMR has emerged, with notable differences in framing in Pakistani and external agency led documents, as well as across stakeholders primarily working on human vs animal health. While framing AMR as a threat to economic growth and human security has achieved high-level political attention and catalysed action from governments in high-income countries, our analysis suggests that conflicting narratives relevant to policymakers in Pakistan may affect policy-making and impede the development and implementation of integrated initiatives needed to tackle AMR. [ABSTRACT FROM AUTHOR]

Comparability of population surveys across countries is key to appraising trends in population health. Achieving this requires deep understanding of the methods used in these surveys to examine the extent to which the measurements are comparable. In this study, we obtained detailed protocols of 8 nationally representative surveys from 2007-2013 from Brazil, Chile, Colombia, Mexico, the United Kingdom(England and Scotland), and the United States--countries that that differ in economic and inequity indicators. Data were collected on sampling frame, sample selection procedures, recruitment, data collection methods, content of interview and examination modules, and measurement protocols. We also assessed their adherence to the World Health Organization's "STEPwise Approach to Surveillance" framework for population health surveys. The surveys, which included half a million participants, were highly comparable on sampling methodology, survey questions, and anthropometric measurements. Heterogeneity was found for physical activity questionnaires and biological samples collection. The common age range included by the surveys was adults aged 18--64 years. The methods used in these surveys were similar enough to enable comparative analyses of the data across the 7 countries. This comparability is crucial in assessing and comparing national and subgroup population health, and to assisting the transfer of research and policy knowledge across countries. [ABSTRACT FROM AUTHOR]

Objective. The objective of this study was to examine cause-specific mortality in patients with PsA compared with the general population and compared with patients with RA. Methods. A cohort study was performed using The Health Improvement Network among patients aged 18-89 years with data from 1994 to 2010. PsA and RA were defined by medical codes, and up to 10 unexposed controls were matched on practice and start date within the practice. Cause of death was classified using categories from UK death statistics. Each death was manually reviewed to ensure appropriate classification. Age- and sex-adjusted hazard ratios (HRs) and multivariable adjusted HRs were calculated using competing risks survival regression. Results. Among patients with PsA (8706), RA (41 752) and unexposed controls (81 573), 470, 7004 and 5269 deaths were observed, respectively. The most common causes of death among all patients were cardiovascular disease, followed by malignancy, respiratory deaths and infection. Cause of death was unknown in ~25%. Among PsA patients, cardiovascular (1.09, 0.91-1.32), respiratory (0.97, 0.79-1.20), malignancy (1.03, 0.86-1.25) and infection deaths (1.05, 0.79-1.39) were not elevated. Among patients with RA, cardiovascular (1.55, 1.44-1.66), respiratory (1.85, 1.72-2.01), malignancy (1.18, 1.08-1.28) and infection deaths (2.21, 2.00-2.44) were significantly elevated compared with population controls. Although less common, suicide deaths were elevated in PsA and RA (HR 3.03 and 2.47, respectively). Conclusion. Overall mortality and cause-specific mortality risk were not elevated among patients with PsA except for suicide deaths. Patients with RA were at increased risk of deaths from cardiovascular, respiratory, [ABSTRACT FROM AUTHOR]

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use. [ABSTRACT FROM AUTHOR]

Background The value of e-learning in medical education is widely recognized but there is little evidence of its value in teaching medical students about public health. Such evidence is needed because medical students' engagement with public health has been low. We present three recent case studies from UK medical schools to illustrate diverse ways in which online approaches can increase medical students' engagement with learning public health. Methods A comparative case study approach was used applying quantitative and qualitative data to examine engagement in terms of uptake/use amongst eligible students, acceptability and perceived effectiveness using an analytic framework based on Seven Principles of Effective Teaching. Results Across the three case studies, most (67-85%) eligible students accessed online materials, and rated them more favourably than live lectures. Students particularly valued opportunities to use e-learning flexibly in terms of time and place. Online technologies offered new ways to consolidate learning of key public health concepts. Although students found contributing to online discussions challenging, it provided opportunities for students to explore concepts in depth and enabled students that were uncomfortable speaking in face-to-face discussions to participate. Conclusions E-learning can be applied in diverse ways that increase medical student engagement with public health teaching. [ABSTRACT FROM AUTHOR]

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries.Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys.Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries.Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese. [ABSTRACT FROM AUTHOR]

Background: previous UK National Audits of Continence Care showed low rates of assessment and treatment of faecal incontinence (FI) in older people.Objective: the 2009 audit assessed adherence to the National Institute for Health and Clinical Excellence guidelines on management of FI and compared care in older versus younger patients.Methods: fifteen older (65+) and 15 younger (18–65) patients with FI were to be audited in hospital (inpatient or outpatient), primary care (PC) and care home sites.Results: data were submitted for n = 2,930 cases from 133 hospitals, n = 1,729 from 97 PC surgeries and n = 693 from 63 care homes. Bowel history was not documented in 41% older versus 24% younger patients in hospitals and 27 versus 19% in PC (both P < 0.001). In older people, there was no documented focused examination in one-third in hospitals, one-half in PC and three-quarters in care homes. Overall, <50% had documented treatment for an identified bowel-related cause of FI. FI was frequently attributed to co-morbidity. Few patients received copies of their treatment plan. Quality-of-life impact was poorly documented particularly in hospitals.Conclusions: this national audit shows deficits in documented assessment, diagnosis and treatment for adults with FI despite availability of clinical guidance. Overall care is significantly poorer for older people. Clinicians, including geriatricians, need to lead on improving care in older people including comprehensive assessment where needed. Improvement in some indicators in older people with successive audits suggests that ongoing national audit with linked information resources can be useful as both monitor and agent for change. [ABSTRACT FROM AUTHOR]

Acute Oak Decline (AOD) is a relatively new decline-disease affecting both native oak species (Quercus robur and Q. petraea) in Britain. The key aim of this study was to describe the symptoms, and signs of AOD, to set a baseline. The second aim was to compare and review the European literature on what appear to be similar disorders on oak. AOD is characterized by four key features: weeping patches more-or-less vertically aligned on oak tree trunks; cracks between bark plates from which dark fluid seeps; inner bark necrosis and the presence (in >90 per cent of cases) of larval galleries of the oak buprestid, Agrilus biguttatus, on the phloem–sapwood interface. In this study, it was noted that although larval galleries were present in the inner bark in 19 of 21 trees, the ‘D-shaped’ exit holes of the adult beetles were seen less frequently on bark plates of affected trees (33 per cent of cases). Similar disorders reported in Europe are compared with AOD in Britain and potential causes of the condition discussed. Based on the unmistakable symptoms, it is hypothesized that AOD is a distinctive, identifiable condition within the broader oak decline syndrome. [ABSTRACT FROM PUBLISHER]

Background: home visits and telephone calls are two often used approaches in transitional care but their differential effects are unknown.Objective: to examine the overall effects of a transitional care programme for discharged medical patients and the differential effects of telephone calls only.Design: randomised controlled trial.Setting: a regional hospital in Hong Kong.Participants: patients discharged from medical units fitting the inclusion criteria (n = 610) were randomly assigned to: control (‘control’, n = 210), home visits with calls (‘home’, n = 196) and calls only (‘call’, n = 204).Intervention: the home groups received alternative home visits and calls and the call groups calls only for 4 weeks. The control group received two placebo calls. The nurse case manager was supported by nursing students in delivering the interventions.Results: the home visit group (after 4 weeks 10.7%, after 12 weeks 21.4%) and the call group (11.8, 20.6%) had lower readmission rates than the control group (17.6, 25.7%). Significance differences were detected in intention-to-treat (ITT) analysis for the home and intervention group (home and call combined) at 4 weeks. In the per-protocol analysis (PPA) results, significant differences were found in all groups at 4 weeks. There was significant improvement in quality of life, self-efficacy and satisfaction in both ITT and PPA for the study groups.Conclusions: this study has found that bundled interventions involving both home visits and calls are more effective in reducing readmissions. Many of the transitional care programmes use all-qualified nurses, and this study reveals that a mixed skills model seems to bring about positive effects as well. [ABSTRACT FROM PUBLISHER]

Varicella-zoster virus (VZV) is the causative agent of both varicella (chickenpox) and herpes zoster (HZ) (shingles). After varicella infection, the virus remains dormant in the host's dorsal ganglia and can reactivate due to waning cell-mediated immunity, causing HZ. Exposure of varicella-immune persons to VZV may boost the host's immune response, resulting in a protective effect against HZ. In this study, we used mathematical models of VZV transmission and HZ development to test the biological hypothesis of “progressive immunity,” originally proposed by Hope-Simpson (Proc R Soc Med. 1965;58:9–20), that cell-mediated protection against HZ increases after each episode of exposure to VZV. Predictions from a model incorporating such a hypothesis were compared with those of other concurrent models proposed for explaining HZ epidemiology. The progressive immunity model fits significantly better the age profile of HZ incidence for Finland (years 2000–2006), Italy (2003–2005), Spain (1997–2004), and the United Kingdom (1991–1992), suggesting that this mechanism may be critical in shaping HZ patterns. The model thus validated is an alternative to VZV models currently used to evaluate the impact of mass immunization programs for varicella and therefore extends the range of tools available to assist policy-makers with the present decision paralysis on the introduction of vaccination. [ABSTRACT FROM PUBLISHER]

Background: mortality in UK care homes is not well described.Objective: to describe 1-year mortality and predictors in older care home residents compared with community residents.Method: cohort study using the THIN primary care database with 9,772 care home and 354,306 community residents aged 65–104 years in 293 English and Welsh general practices in 2009.Results: a total of 2,558 (26.2%) care home and 11,602 (3.3%) community residents died within 1 year. The age and sex standardised mortality ratio for nursing homes was 419 (95% CI: 396–442) and for residential homes was 284 (266–302). Age-related increases in mortality were less marked in care homes than community. Comorbidities and identification as inappropriate for chronic disease management targets predicted mortality in both settings, but associations were weaker in care homes. The number of drug classes prescribed and primary care contact were the strongest clinical predictors of mortality in care homes.Conclusions: older care home residents experience high mortality. Age and diagnostic characteristics are weaker predictors of risk of death within care homes than the community. Measures of primary care utilisation may be useful proxies for frailty and improve difficult end of life care decisions in care homes. [ABSTRACT FROM PUBLISHER]

Background: Many popular childcare books recommend feeding babies to a schedule, but no large-scale study has ever examined the effects of schedule-feeding. Here, we examine the relationship between feeding infants to a schedule and two sets of outcomes: mothers’ wellbeing, and children’s longer-term cognitive and academic development. Methods: We used a sample of 10 419 children from the Avon Longitudinal Study of Parents and Children, a cohort study of children born in the 1990s in Bristol, UK. Outcomes were compared by whether babies were fed to a schedule at 4 weeks. Maternal wellbeing indicators include measures of sleep sufficiency, maternal confidence and depression, collected when babies were between 8 weeks and 33 months. Children’s outcomes were measured by standardized tests at ages 5, 7, 11 and 14, and by IQ tests at age 8. Results: Mothers who fed to a schedule scored more favourably on all wellbeing measures except depression. However, schedule-fed babies went on to do less well academically than their demand-fed counterparts. After controlling for a wide range of confounders, schedule-fed babies performed around 17% of a standard deviation below demand-fed babies in standardized tests at all ages, and 4 points lower in IQ tests at age 8 years. Conclusions: Feeding infants to a schedule is associated with higher levels of maternal wellbeing, but with poorer cognitive and academic outcomes for children. [ABSTRACT FROM PUBLISHER]

Reserve and National Guard forces have been mobilized to an unprecedented degree in recent overseas conflicts. There is concern that rates of psychological problems may continue to rise for many years after deployment. The authors conducted a cohort study of 552 United Kingdom Reservists who deployed to Iraq in 2003 and 391 nondeployed Reservists. Measures of mental health and social functioning were collected a mean of 16 months and 4.8 years after return from possible deployment. At the first follow-up, deployment was associated with increased common mental disorder, post-traumatic stress disorder (PTSD), and poor general health. By the second follow-up, those who had deployed were no longer at increased risk for common mental disorder or poor general health and had good levels of social functioning. However, those who deployed continued to have over twice the odds of PTSD (odds ratio = 2.42, 95% confidence interval: 1.04, 5.62) and were more likely to report actual or serious consideration of separation from their partner. In conclusion, the authors found that the majority of mental health and social problems following deployment are transient. However, Reservists who deployed in the Iraq War remain at increased risk of PTSD and relationship problems 5 years after their tour of duty. [ABSTRACT FROM AUTHOR]