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    COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records
    Thygesen, JH ; Tomlinson, C ; Hollings, S ; Mizani, MA ; Handy, A ; Akbari, A ; Banerjee, A ; Cooper, J ; Lai, AG ; Li, K ; Mateen, BA ; Sattar, N ; Sofat, R ; Torralbo, A ; Wu, H ; Wood, A ; Sterne, JAC ; Pagel, C ; Whiteley, WN ; Sudlow, C ; Hemingway, H ; Denaxas, S (ELSEVIER, 2022-07-01)
    BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.
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    Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review
    Jones, OT ; Matin, RN ; van der Schaar, M ; Bhayankaram, KP ; Ranmuthu, CK ; Islam, MS ; Behiyat, D ; Boscott, R ; Calanzani, N ; Emery, J ; Williams, HC ; Walter, FM (ELSEVIER, 2022-06-01)
    Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation.
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    Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study
    Piernas, C ; Patone, M ; Astbury, NM ; Gao, M ; Sheikh, A ; Khunti, K ; Shankar-Hari, M ; Dixon, S ; Coupland, C ; Aveyard, P ; Hippisley-Cox, J ; Jebb, SA (ELSEVIER SCIENCE INC, 2022-07-01)
    BACKGROUND: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England. METHODS: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m2) after vaccination. FINDINGS: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. INTERPRETATION: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease. FUNDING: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.
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    Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis
    Seidu, S ; Cebrian, A ; Kunutsor, SK ; Khunti, K (ELSEVIER SCI LTD, 2022-10-01)
    BACKGROUND: Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. METHODS: Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. RESULTS: Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31-1.55), 1.47 (1.31-1.65), 1.59 (1.39-1.82), and 1.34 (1.15-1.56), respectively. The respective estimates were 1.68 (1.15-2.45), 1.40 (0.90-2.18), 1.41 (1.24-1.61) and 1.32 (1.09-1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17-69.19), 1.31 (0.10-16.54) and 0.35 (0.12-1.05), respectively. CONCLUSIONS: ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM. PROSPERO Registration: CRD42022324537.
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    Assessing and addressing diabetes distress among adults with type 2 diabetes: An online survey of Australian general practitioners.
    McMorrow, R ; Hunter, B ; Hendrieckx, C ; Speight, J ; Emery, J ; Manski-Nankervis, J-A (Elsevier BV, 2022-10)
    AIM: Diabetes distress is experienced by up to 36% of adults with type 2 diabetes. Australian type 2 diabetes guidelines recommend annual assessment of diabetes distress in general practice. This study explores general practitioners' knowledge, current practice, and factors influencing implementation of guidelines, including Person Reported Outcome Measure (PROM) use. METHODS: A cross-sectional online survey was disseminated via e-mail to 4776 Australian general practitioners listed on the Australasian Medical Publishing Company database. RESULTS: 264 (5%) surveys were returned. 75% indicated that general practitioners were the most appropriate professionals to assess diabetes distress. Sixteen percent reported asking about diabetes distress during type 2 diabetes consultations more than half the time, with 13% using a PROM more than half the time: 64% use the Kessler-10, and 1.9% use the Problem Areas in Diabetes (PAID) scale. While general practitioners had positive beliefs about the consequences of assessing and addressing diabetes distress, they also reported barriers in motivation, environment, and knowledge of guidelines. CONCLUSION: Most respondents endorsed general practitioners' role in assessing diabetes distress, but few ask about or assess diabetes distress in routine consultations. To support uptake of guideline recommendations for diabetes-specific PROM use, environmental factors, specifically time, need to be addressed.
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    Self-reported walking pace, polygenic risk scores and risk of coronary artery disease in UK biobank
    Zaccardi, F ; Timmins, IR ; Goldney, J ; Dudbridge, F ; Dempsey, PC ; Davies, MJ ; Khunti, K ; Yates, T (ELSEVIER SCI LTD, 2022-11-01)
    BACKGROUND AND AIMS: Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. METHODS AND RESULTS: We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006-Feb/2021. In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30-3.13) in women; 9.60% (8.62-10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81-1.71) in women; 3.63% (2.58-4.67) in men] than lower [0.76% (0.59-0.93) and 2.37% (1.96-2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793-0.808) in women; 0.732 (0.728-0.737) in men. CONCLUSION: Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.
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    Differences in the risk of cardiovascular disease across ethnic groups: UK Biobank observational study
    Razieh, C ; Zaccardi, F ; Miksza, J ; Davies, MJ ; Hansell, AL ; Khunti, K ; Yates, T (ELSEVIER SCI LTD, 2022-11-01)
    BACKGROUND AND AIMS: To describe sociodemographic, lifestyle, environmental and traditional clinical risk factor differences between ethnic groups and to investigate the extent to which such differences confound the association between ethnic groups and the risk of cardiovascular disease (CVD) METHODS AND RESULTS: A total of 440,693 white European (55.9% women), 7305 South Asian (48.6%) and 7628 black African or Caribbean (57.7%) people were included from UK Biobank. Associations between ethnicity and cardiovascular outcomes (composite of non-fatal stroke, non-fatal myocardial infarction and CVD death) were explored using Cox-proportional hazard models. Models were adjusted for sociodemographic, lifestyle, environmental and clinical risk factors. Over a median (IQR) of 12.6 (11.8, 13.3) follow-up years, there were 22,711 (5.15%) cardiovascular events in white European, 463 (6.34%) in South Asian and 302 (3.96%) in black African or Caribbean individuals. For South Asian people, the cardiovascular hazard ratio (HR) compared to white European people was 1.28 (99% CI [1.16, 1.43]). For black African or Caribbean people, the HR was 0.80 (0.66, 0.97). The elevated risk of CVD in South Asians remained after adjusting for differences in sociodemographic, lifestyle, environmental and clinical factors, whereas the lower risk in black African or Caribbean was largely attenuated. CONCLUSIONS: South Asian, but not black African or Caribbean individuals, have a higher risk of CVD compared to white European individuals. This higher risk in South Asians was independent of sociodemographic, lifestyle, environmental and clinical factors.
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    Experience of COVID-19 Vaccination among Primary Healthcare Workers in Hong Kong: A Qualitative Study
    Ng, KM ; Chu, TK ; Lau, P (MDPI, 2022-09-01)
    Studies show that coronavirus disease 2019 (COVID-19) vaccine hesitancy exists among healthcare workers (HCWs). Past personal experiences of vaccination, such as the seasonal influenza vaccination, influence individuals' intention to receive future vaccinations. This study aimed to explore the experience of COVID-19 vaccination among primary care HCWs in Hong Kong. A qualitative study using semi-structured interviews was conducted. Twenty-eight HCWs (ten doctors, ten nurses, and eight supporting staff) working in nine government-funded primary care clinics in Hong Kong who had completed at least one dose of COVID-19 vaccination were interviewed. Four themes were generated, namely, the cognitive and emotional battle of vaccine hesitancy, catalysts for vaccine acceptance, blasting vaccination myths, and being a positive influence. Providing timely, adequate, and transparent vaccine information and addressing the specific concerns of HCWs about the COVID-19 vaccine could enhance their vaccination uptake in future. Specific vaccine promotion strategies, such as the sharing of vaccination experiences targeted at different subgroups of HCWs, may improve vaccine acceptance through informational social influence.
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    The Potential Impact of a Public Health Approach to Improving the Physical Health of People Living with Mental Illness
    Roberts, R ; Johnson, C ; Hopwood, M ; Firth, J ; Jackson, K ; Sara, G ; Allan, J ; Calder, R ; Manger, S (MDPI, 2022-09-01)
    With already wide disparities in physical health and life expectancy, COVID-19 presents people with mental illness with additional threats to their health: decreased access to health services, increased social isolation, and increased socio-economic disadvantage. Each of these factors has exacerbated the risk of poor health and early death for people with mental illness post-COVID-19. Unless effective primary care and preventative health responses are implemented, the physical illness epidemic for this group will increase post the COVID-19 pandemic. This perspective paper briefly reviews the literature on the impact of COVID-19 on service access, social isolation, and social disadvantage and their combined impact on physical health, particularly cancer, respiratory diseases, heart disease, smoking, and infectious diseases. The much-overlooked role of poor physical health on suicidality is also discussed. The potential impact of public health interventions is modelled based on Australian incidence data and current research on the percentage of early deaths of people living with mental illnesses that are preventable. Building on the lessons arising from services' response to COVID-19, such as the importance of ensuring access to preventive, screening, and primary care services, priority recommendations for consideration by public health practitioners and policymakers are presented.
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    A retrospective cohort study predicting and validating impact of the COVID-19 pandemic in individuals with chronic kidney disease
    Dashtban, A ; Mizani, MA ; Denaxas, S ; Nitsch, D ; Quint, J ; Corbett, R ; Mamza, JB ; Morris, T ; Mamas, M ; Lawlor, DA ; Khunti, K ; Sudlow, C ; Hemingway, H ; Banerjee, A (ELSEVIER SCIENCE INC, 2022-09-01)
    Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe COVID-19, but analyses across CKD stages, and comorbidities are lacking. In prevalent and incident CKD, we investigated comorbidities, baseline risk, COVID-19 incidence, and predicted versus observed one-year excess death. In a national dataset (NHS Digital Trusted Research Environment [NHSD TRE]) for England encompassing 56 million individuals), we conducted a retrospective cohort study (March 2020 to March 2021) for prevalence of comorbidities by incident and prevalent CKD, SARS-CoV-2 infection and mortality. Baseline mortality risk, incidence and outcome of infection by comorbidities, controlling for age, sex and vaccination were assessed. Observed versus predicted one-year mortality at varying population infection rates and pandemic-related relative risks using our published model in pre-pandemic CKD cohorts (NHSD TRE and Clinical Practice Research Datalink [CPRD]) were compared. Among individuals with CKD (prevalent:1,934,585, incident:144,969), comorbidities were common (73.5% and 71.2% with one or more condition[s] in respective data sets, and 13.2% and 11.2% with three or more conditions, in prevalent and incident CKD), and associated with SARS-CoV-2 infection, particularly dialysis/transplantation (odds ratio 2.08, 95% confidence interval 2.04-2.13) and heart failure (1.73, 1.71-1.76), but not cancer (1.01, 1.01-1.04). One-year all-cause mortality varied by age, sex, multi-morbidity and CKD stage. Compared with 34,265 observed excess deaths, in the NHSD-TRE and CPRD databases respectively, we predicted 28,746 and 24,546 deaths (infection rates 10% and relative risks 3.0), and 23,754 and 20,283 deaths (observed infection rates 6.7% and relative risks 3.7). Thus, in this largest, national-level study, individuals with CKD have a high burden of comorbidities and multi-morbidity, and high risk of pre-pandemic and pandemic mortality. Hence, treatment of comorbidities, non-pharmaceutical measures, and vaccination are priorities for people with CKD and management of long-term conditions is important during and beyond the pandemic.