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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Associations between types and sources of dietary carbohydrates and cardiovascular disease risk: a prospective cohort study of UK Biobank participants
Background: Recent studies have reported that the associations between dietary carbohydrates and cardiovascular disease (CVD) may depend on the quality, rather than the quantity, of carbohydrates consumed. This study aimed to assess the associations between types and sources of dietary carbohydrates and CVD incidence. A secondary aim was to examine the associations of carbohydrate intakes with triglycerides within lipoprotein subclasses. Methods: A total of 110,497 UK Biobank participants with ≥ two (maximum five) 24-h dietary assessments who were free from CVD and diabetes at baseline were included. Multivariable-adjusted Cox regressions were used to estimate risks of incident total CVD (4188 cases), ischaemic heart disease (IHD; 3138) and stroke (1124) by carbohydrate intakes over a median follow-up time of 9.4 years, and the effect of modelled dietary substitutions. The associations of carbohydrate intakes with plasma triglycerides within lipoprotein subclasses as measured by nuclear magnetic resonance (NMR) spectroscopy were examined in 26,095 participants with baseline NMR spectroscopy measurements. Results: Total carbohydrate intake was not associated with CVD outcomes. Free sugar intake was positively associated with total CVD (HR; 95% CI per 5% of energy, 1.07;1.03–1.10), IHD (1.06;1.02–1.10), and stroke (1.10;1.04–1.17). Fibre intake was inversely associated with total CVD (HR; 95% CI per 5 g/d, 0.96;0.93–0.99). Modelled isoenergetic substitution of 5% of energy from refined grain starch with wholegrain starch was inversely associated with total CVD (0.94;0.91–0.98) and IHD (0.94;0.90–0.98), and substitution of free sugars with non-free sugars was inversely associated with total CVD (0.95;0.92–0.98) and stroke (0.91;0.86–0.97). Free sugar intake was positively associated with triglycerides within all lipoproteins. Conclusions: Higher free sugar intake was associated with higher CVD incidence and higher triglyceride concentrations within all lipoproteins. Higher fibre intake and replacement of refined grain starch and free sugars with wholegrain starch and non-free sugars, respectively, may be protective for incident CVD.
The early use of Antibiotics for At-risk children with InfluEnza in Primary Care (the ARCHIE programme)
Background: Influenza and influenza-like illness place significant burden on the NHS. Children with underlying health conditions are vulnerable to developing bacterial complications. Objective: To strengthen the evidence base underlying antibiotic use in at-risk children with influenza-like illness. Design: This programme comprised five separate work packages. Work package A investigated published and unpublished data from previously published literature and work package B explored attitudes of parents and general practitioners to influenza-like illness and antibiotics in at-risk children. This was followed by a clinical trial to assess the effectiveness of early co-amoxiclav (Augmentin®, GlaxoSmithKline UK) use at reducing reconsultation due to clinical deterioration (work package C), a nested sub-study to examine bacterial carriage indicators of antibiotic resistance (work package D) and a within-trial economic evaluation and clinical risk prediction analysis (work package E). Setting: Interviews were conducted by telephone with general practitioners across the UK and parents/ guardians in England (work package B). We conducted the clinical trial (work package C and nested work packages D and E) in general practices and ambulatory care services in England and Wales. Participants: General practitioners and parents/guardians of at-risk children who previously had influenza-like illness participated in work package B. At-risk children with influenza-like illness aged 6 months to 12 years participated in work packages C and E and optionally in work package D. Interventions: The intervention for the clinical trial was a 5-day course of co-amoxiclav 400/57 with dosing regimens based on British National Formulary guidance. Main outcome measures: Hospital admission (work package A); findings from semi-structured interviews with patients and health-care professionals (work package B); proportion of patients who reconsulted owing to clinical deterioration (work package C); respiratory bacterial carriage and antibiotic resistance of potentially pathogenic respiratory tract bacteria at 3, 6, 9 and 12 months (work package D); and risk factors for reconsultation owing to clinical deterioration, quality of life (EuroQol-5 Dimensions, three-level youth version), symptoms (Canadian Acute Respiratory Infection and Flu Scale), health-care use and costs (work package E). Review methods: For work package A, we searched the MEDLINE, MEDLINE In-Process, EMBASE, Science Citation Index and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases until 3 April 2013 with no language restrictions and requested unpublished data from authors of studies which had collected but not published relevant data. We included studies involving children up to 18 years of age with influenza or influenza-like illness from primary or ambulatory care settings. We used univariable meta-analysis methods to calculate odds ratios with 95% confidence intervals for individual risk factors. We reported our systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 statement. Results: Work package A analysed data from 28 articles reporting data from 27 studies. Neurological disorders, sickle cell disease, immunosuppression, diabetes and an age of <2 years were risk factors for hospital admission. Work package B interviewed 41 general practitioners and found that decision-making in at-risk children with influenza-like illness varies considerably. Parents/guardians were interviewed for work package B and spoke of how quickly their at-risk child could deteriorate. They were supportive of antibiotic use while being aware of antibiotic resistance. The trial (work package C) recruited 271 at-risk children. Primary outcome data were available for 265 children. There was no evidence of benefit from treatment with co-amoxiclav versus placebo (adjusted risk ratio 1.16, 95% confidence interval 0.75 to 1.80). Work package D collected 285 additional throat swabs over 12 months. At 3 months, the proportion of Haemophilus influenzae isolates was greater in the placebo than co-amoxiclav group (29% vs. 18%). No association was found between antibiotic resistance and early co-amoxiclav use. No clinical features were significantly associated with risk of reconsultation due to clinical deterioration except respiratory rate (coefficient 0.046, 95% confidence interval 0.010 to 0.081). Work package E found no evidence that early co-amoxiclav treatment improves quality of life or reduces health-care use and costs. Total costs per patient were highly skewed in both groups (co-amoxiclav: median £4, range £4–5258; placebo: median £0, range £0–5177). Limitations: We were not able to recruit our target sample size for the trial. This impacted the data available for microbiology, health economics and risk reduction score analyses. Conclusions: Our results do not support early antibiotic prescribing to at-risk children with influenza-like illness during influenza season. Future work: Further research is required to determine if antibiotic treatment would be beneficial during periods of higher influenza activity such as influenza pandemics, to identify children who would gain most clinical benefit and to better understand families’ reconsultation decisions. Trial registration: This trial is registered as ISRCTN70714783 and EudraCT 2013-002822-21.
Crafting Tempo and Timeframes in Qualitative Longitudinal Research: Case Studies From Health Research
Qualitative Longitudinal Research (QLR) is a dynamic and evolving methodology using time as a lens to inform study design, data collection and analysis. A key feature of QLR is the collection of data on more than one occasion, often described as waves or time points. Thus, researchers embarking on designing a new study need to consider several key features including the study duration (timeframe) and the frequency and intensity of data collection (tempo). Yet, how to embed these features in practice is not well described. Leveraging the intensive-extensive temporal plane of time, we explore research approaches employing both shorter and longer timeframes, as well as intensive and extensive tempos. Drawing on six studies that we have conducted, we discuss four pivotal aspects including: (i) crafting intensive-extensive tempo and timeframes; (ii) defining baseline and closure points; (iii) planning for flexibility; and (iv) working ethically within a temporal lens. By examining and critically analysing these case studies through the lens of the intensive-extensive plane of time, this article aspires to offer insights for researchers interested in using the QLR design in healthcare. We thus aim to prepare researchers for embedding these features during the research process.
Household wealth, neighbourhood deprivation and frailty amongst middle-aged and older adults in England: a longitudinal analysis over 15 years (2002-2017).
BACKGROUND: frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. OBJECTIVE: to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. DESIGN: population-based cohort study. SETTING: communities in England. SUBJECTS: in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. METHODS: multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. RESULTS: the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0-34.6%] and 11.7 (11.1-12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2-1.3) and 2.2 (95% CI = 2.1-2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. CONCLUSIONS: in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours.
The effect of lengthening life expectancy on future pension and long-term care expenditure in England, 2007 to 2032.
The aim of this analysis is to examine the effect of different assumptions about future trends in life expectancy (LE) on the sustainability of the pensions and long-term care (LTC) systems. The context is the continuing debate in England about the reform of state pensions and the reform of the system for financing care and support. Macro and micro simulation models are used to make projections of future public expenditure on LTC services for older people and on state pensions and related benefits, making alternative assumptions on increases in future LE. The projections cover the period 2007 to 2032 and relate to England. Results are presented for a base case and for specified variants to the base case. The base case assumes that the number of older people by age and gender rises in line with the Office for National Statistics' principal 2006-based population projection for England. It also assumes no change in disability rates, no changes in patterns of care, no changes in policy and rises in unit care costs and real average earnings by 2 per cent per year. Under these assumptions public expenditure on pensions and related benefits is projected to rise from 4.7 per cent of Gross Domestic Product (GDP) in 2007 to 6.2 per cent of GDP in 2032 and public expenditure on LTC from 0.9 per cent of GDP in 2007 to 1.6 per cent of GDP in 2032. Under a very high LE variant to the GAD principal projection, however, public expenditure on pensions and related benefits is projected to reach 6.8 per cent of GDP in 2032 and public expenditure on LTC 1.7 per cent of GDP in 2032. Policymakers developing reform proposals need to recognise that, since future LE is inevitably uncertain and since variant assumptions about future LE significantly affect expenditure projections, there is a degree of uncertainty about the likely impact of demographic pressures on future public expenditure on pensions and LTC.
Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales
Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32–1.51)), older adults (≥80 years vs 18–49 years; 10.43 (8.06–13.50)), underweight (BMI <18.5 vs BMI 25.0–29.9; 2.94 (2.51–3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15–10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23–1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21–1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies—Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.
Interim 2023/2024 Season Influenza Vaccine Effectiveness in Primary and Secondary Care in the United Kingdom
Background: We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England. Methods: A test negative design was used to estimate vaccine effectiveness. Results: Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2–17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18–64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over. Conclusions: During a period of co-circulation of influenza A(H1N1)pdm09 and A(H3N2) in the United Kingdom, evidence for effectiveness of the influenza vaccine in both children and adults was found.
Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts
SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5–17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5–11 year-olds were less likely to receive their first vaccine compared to 16–17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06–0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13–0.29).
End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain
Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2–13 (and 14–15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. Methods: End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. Methods: Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: −6% to 54%). VE for those aged 18–64, who largely received cell-based vaccines, was 47% (95% CI: 37%–56%). Overall VE for 2–17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%–76%). Conclusion: The paper provides evidence of moderate influenza VE in 2022/23.
Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: a comparison of England and Denmark using the OpenSAFELY platform and National Registry Data.
OBJECTIVES: To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021. DESIGN: Time-series studies in England and Denmark. SETTING: With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data. PARTICIPANTS: We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria. PRIMARY OUTCOME MEASURES: Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE). RESULTS: We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile. CONCLUSIONS: Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.
The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal
Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.
Efficacy of a culturally adapted, cognitive behavioural therapy-based intervention for postnatal depression in British south Asian women (ROSHNI-2): a multicentre, randomised controlled trial
Background: Postnatal depression necessitates timely and effective interventions to mitigate adverse maternal and child outcomes in the short term and over the life course. British south Asian women with depression are often underserved and undertreated due to stigma, language barriers, and cultural barriers. This trial aimed to test the clinical efficacy of a culturally adapted, group cognitive behavioural therapy (CBT)-based intervention, the Positive Health Programme (PHP), delivered by non-specialist health workers for postnatal depression in British south Asian women. Methods: This study was a randomised controlled trial, with culturally adapted recruitment and an internal pilot, comparing the PHP (intervention group) with treatment as usual (control group) in British south Asian women with postnatal depression. The study was conducted at five centres across the UK. Participants were aged 16 years or older, met the DSM-5 criteria for depression, and had infants aged 0–12 months. Randomisation (1:1) was stratified by centre, with a block size of 18, and was done through an independent remote telephone service. The PHP was delivered over 12 group sessions in 4 months. The primary outcome was recovery from depression (defined as a Hamilton Depression Rating Scale [HDRS] score ≤7) at 4 months after randomisation, and an assessment was also done at 12 months. Analysis was on an intention-to-treat basis including only participants with non-missing outcome data; we used a random-effects logistic regression model including fixed covariates for study site, baseline depression severity (HDRS score), parity, and years in education and a random coefficient for therapy group. This trial is registered with the ISRCTN (ISRCTN10697380). Findings: Of the 9136 individuals approached for recruitment between Feb 8, 2017, and March 29, 2020, 4296 women were eligible for and consented to screening, among whom 732 screened positive and were randomly allocated: 368 (50%) to the PHP group and 364 (50%) to the control group. Participants were mostly of Pakistani (397 [55%] of 719 with available data), Indian (176 [24%]), or Bangladeshi ethnicity (127 [18%]), with an overall mean age of 31·4 years (SD 5·2), with their youngest infants having a mean age of 23·6 weeks (14·2). At 4 months from randomisation, the proportion of participants who showed recovery from depression on the HDRS was significantly higher in the PHP group (138 [49%] of 281) than in the control group (105 [37%] of 281; adjusted odds ratio 1·97 [95% CI 1·26–3·10]). At the 12-month follow-up, this difference was no longer significant (1·02 [95% CI 0·62–1·66]). Interpretation: In British south Asian women with postnatal depression, a culturally adapted group CBT-based intervention could aid in quicker recovery from depression compared with treatment as usual. Further research is needed to identify how to sustain the treatment effect and establish strategies for scale-up. Funding: UK National Institute for Health and Care Research.
Getting rights right: Implementing 'Martha's Rule'
The UK government has recently committed to adopting a new policy - dubbed 'Martha's Rule' - which has been characterised as providing patients the right to rapidly access a second clinical opinion in urgent or contested cases. Support for the rule emerged following the death of Martha Mills in 2021, after doctors failed to admit her to intensive care despite concerns raised by her parents. We argue that framing this issue in terms of patient rights is not productive, and should be avoided. Insofar as the ultimate goal of Martha's Rule is the provision of a clinical service that protects patient safety, an approach that focuses on the obligations of the health system - rather than the individual rights of patients - will better serve this goal. We outline an alternative approach that situates rapid clinical review as part of a suite of services aimed at enhancing and protecting patient care. This approach would make greater progress towards addressing the difficult systemic issues that Martha's Rule does not, while also better engaging with the constraints of clinical practice.
Navigating epistemic challenges: Self-initiated self-repair in weight loss discussions within clinical settings
This paper focuses on the phenomenon of self-initiated self-repair in weight loss discussions within clinical settings. It shows that one of the primary functions of self-repair is to manage epistemics in talk. The study explores repair operations and techniques, shedding light on the linguistic resources employed by doctors and patients to modify knowledge claims in relation to their interactional objectives, the speaker's epistemic status, and the epistemic stance expressed by the interlocutor. Throughout the paper, we demonstrate how self-initiated self-repairs contribute to achieving epistemic balance and congruence in talk between healthcare providers and seekers, supporting the smooth delivery of unsolicited weight loss advice. Data are in British English.