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    Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study
    Ayoubkhani, D ; Bermingham, C ; Pouwels, KB ; Glickman, M ; Nafilyan, V ; Zaccardi, F ; Khunti, K ; Alwan, NA ; Walker, AS (BMJ PUBLISHING GROUP, 2022-05-18)
    OBJECTIVE: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination. DESIGN: Observational cohort study. SETTING: Community dwelling population, UK. PARTICIPANTS: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection. MAIN OUTCOME MEASURE: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. RESULTS: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval -18.6% to -6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval -0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval -14.1% to -3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (-1.2% to -0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination. CONCLUSIONS: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.
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    Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis.
    Martin, CA ; Pan, D ; Melbourne, C ; Teece, L ; Aujayeb, A ; Baggaley, RF ; Bryant, L ; Carr, S ; Gregary, B ; Gupta, A ; Guyatt, AL ; John, C ; McManus, IC ; Nazareth, J ; Nellums, LB ; Reza, R ; Simpson, S ; Tobin, MD ; Woolf, K ; Zingwe, S ; Khunti, K ; Abrams, KR ; Gray, LJ ; Pareek, M ; UK-REACH Study Collaborative Group, ; Geng, EH (Public Library of Science (PLoS), 2022-05)
    BACKGROUND: Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. METHODS AND FINDINGS: We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. CONCLUSIONS: We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. TRIAL REGISTRATION: The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).
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    The impact of the COVID-19 pandemic on glycaemic control in people with diabetes: A systematic review and meta-analysis
    O'Mahoney, LL ; Highton, PJ ; Kudlek, L ; Morgan, J ; Lynch, R ; Schofield, E ; Sreejith, N ; Kapur, A ; Otunla, A ; Kerneis, S ; James, O ; Rees, K ; Curtis, F ; Khunti, K ; Hartmann-Boyce, J (WILEY, 2022-06-20)
    AIM: To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID-19) pandemic and lockdown (LD) on glycaemic control in people with diabetes. MATERIALS AND METHODS: We searched multiple databases up to 2 February 2021 for studies reporting HbA1c, time in range (TIR), average or fasting glucose, severe hypoglycaemia and diabetic ketoacidosis. Data were pooled using random effects meta-analysis and are presented as mean difference (MD) with 95% confidence intervals (CI). This review was preregistered on PROSPERO (CRD42020179319). RESULTS: We include 59 studies; 44 (n = 15 464) were included in quantitative syntheses and 15 were narratively synthesized. Pooled data were grouped by diabetes type. Results from 28 studies (n = 5048 type 1 diabetes [T1D] and combined diabetes participants) showed that TIR increased during LD compared with before LD (MD 2.74%, 95% CI 1.80% to 3.69%). Data from 10 studies (n = 1294 T1D participants) showed that TIR increased after LD compared with before LD (MD 5.14%, 95% CI 3.12% to 7.16%). Pooled results from 12 studies (n = 4810 T1D and type 2 diabetes participants) resulted in average glucose decreasing after LD compared with before LD (MD -6.86 mg/dl, 95% CI -8.54 to -5.18). Results for other outcomes, including HbA1c, were not statistically significantly different. CONCLUSIONS: The COVID-19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, although there was insufficient evidence to suggest that this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high-income countries; more research is needed in less advantaged populations.
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    The Effects of Omega-3 Supplementation on Depression in Adults with Cardiometabolic Disease: A Systematic Review of Randomised Control Trials
    Arsenyadis, F ; Ahmad, E ; Redman, E ; Yates, T ; Davies, M ; Khunti, K (MDPI, 2022-05-01)
    BACKGROUND: Omega-3 polyunsaturated fatty acids' concurrent benefits for cardiometabolic and mental health are equivocal. Despite lack of evidence, up to a third of adults consume Omega-3 supplements. No review has yet been published to report effect on depression in this cardiometabolic population. METHODS: We conducted a systematic review of double-blinded, controlled randomised trials to investigate the safety and effect of Omega-3 supplementation on depression scores in people with cardiometabolic diseases. Primary outcome was change in depression scores versus placebo. Secondary outcomes were side-effects, concurrent medication and adherence. RESULTS: Seven trials reporting on 2575 (672 female) adults aged 39-73 were included. Omega-3 dosages ranged from 1-3 g with an intervention duration of 10-48 weeks. Six out of seven trials found no statistically or clinically significant change to depression scores compared to placebo. One trial favoured intervention (Relative Risk Reduction: 47.93%, 95% CI: 24.89-63.98%, p < 0.001). Sub-analyses showed clinically meaningful reductions in depression scores for those on antidepressants (Intervention: 20.9 (SD: 7.1), Placebo: 24.9 (SD: 8.5) p < 0.05) or with severe depression (-1.74; 95% CI -3.04 to -0.05, p < 0.05) in two separate trials. Side effects were comparable between treatment arms. CONCLUSIONS: Omega-3 supplementation is safe to use but not superior to placebo for depression in adults with concurrent cardiometabolic disease.
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    Prevalence of co-morbidities and their association with mortality in patients withCOVID-19: A systematic review and meta-analysis
    Singh, AK ; Gillies, CL ; Singh, R ; Singh, A ; Chudasama, Y ; Coles, B ; Seidu, S ; Zaccardi, F ; Davies, MJ ; Khunti, K (WILEY, 2020-07-16)
    AIM: To estimate the prevalence of both cardiometabolic and other co-morbidities in patients with COVID-19, and to estimate the increased risk of severity of disease and mortality in people with co-morbidities. MATERIALS AND METHODS: Medline, Scopus and the World Health Organization website were searched for global research on COVID-19 conducted from January 2019 up to 23 April 2020. Study inclusion was restricted to English language publications, original articles that reported the prevalence of co-morbidities in individuals with COVID-19, and case series including more than 10 patients. Eighteen studies were selected for inclusion. Data were analysed using random effects meta-analysis models. RESULTS: Eighteen studies with a total of 14 558 individuals were identified. The pooled prevalence for co-morbidities in patients with COVID-19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension, 11.5% (9.7 to 13.4) for diabetes, and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD). For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease and cancer, the pooled prevalences were all less than 4%. With the exception of cerebrovascular disease, all the other co-morbidities presented a significantly increased risk for having severe COVID-19. In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease and cancer. CONCLUSIONS: In individuals with COVID-19, the presence of co-morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID-19 and mortality. These findings have important implications for public health with regard to risk stratification and future planning.
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    The impact of COVID-19 restrictions on accelerometer-assessed physical activity and sleep in individuals with type 2 diabetes
    Rowlands, AV ; Henson, JJ ; Coull, NA ; Edwardson, CL ; Brady, E ; Hall, A ; Khunti, K ; Davies, M ; Yates, T (WILEY, 2021-03-23)
    AIMS: Restrictions during the COVID-19 crisis will have impacted on opportunities to be active. We aimed to (a) quantify the impact of COVID-19 restrictions on accelerometer-assessed physical activity and sleep in people with type 2 diabetes and (b) identify predictors of physical activity during COVID-19 restrictions. METHODS: Participants were from the UK Chronotype of Patients with type 2 diabetes and Effect on Glycaemic Control (CODEC) observational study. Participants wore an accelerometer on their wrist for 8 days before and during COVID-19 restrictions. Accelerometer outcomes included the following: overall physical activity, moderate-to-vigorous physical activity (MVPA), time spent inactive, days/week with ≥30-minute continuous MVPA and sleep. Predictors of change in physical activity taken pre-COVID included the following: age, sex, ethnicity, body mass index (BMI), socio-economic status and medical history. RESULTS: In all, 165 participants (age (mean±S.D = 64.2 ± 8.3 years, BMI=31.4 ± 5.4 kg/m2 , 45% women) were included. During restrictions, overall physical activity was lower by 1.7 mg (~800 steps/day) and inactive time 21.9 minutes/day higher, but time in MVPA and sleep did not statistically significantly change. In contrast, the percentage of people with ≥1 day/week with ≥30-minute continuous MVPA was higher (34% cf. 24%). Consistent predictors of lower physical activity and/or higher inactive time were higher BMI and/or being a woman. Being older and/or from ethnic minorities groups was associated with higher inactive time. CONCLUSIONS: Overall physical activity, but not MVPA, was lower in adults with type 2 diabetes during COVID-19 restrictions. Women and individuals who were heavier, older, inactive and/or from ethnic minority groups were most at risk of lower physical activity during restrictions.
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    Improved diabetes-related distress and self-efficacy outcomes in a self-management digital programme for people with type 2 diabetes, myDESMOND
    Hadjiconstantinou, M ; Barker, MM ; Brough, C ; Schreder, S ; Northern, A ; Stribling, B ; Khunti, K ; Davies, MJ (WILEY, 2021-03-15)
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    Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial
    Ahmad, E ; Waller, HL ; Sargeant, JA ; Webb, MA ; Htike, ZZ ; McCann, GP ; Gulsin, G ; Khunti, K ; Yates, T ; Henson, J ; Davies, MJ ; Webb, DR (WILEY, 2021-02-26)
    The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26-week, randomized, active-comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m2 , HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1-alpha (SDF-1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between-group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between-group differences in CPCs, nitric oxide, C-reactive protein, interleukin-6, tumour necrosis factor alpha and advanced glycation end-products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF-1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis-generating. Purposive trials are required to examine these findings further.
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    Rates and estimated cost of primary care consultations in people diagnosed with type 2 diabetes and comorbidities: A retrospective analysis of 8.9 million consultations
    Coles, B ; Zaccardi, F ; Seidu, S ; Gillies, CL ; Davies, MJ ; Hvid, C ; Khunti, K (WILEY, 2021-02-19)
    AIMS: To determine whether telephone and face-to-face primary care consultation rates, costs, and temporal trends during 2000 to 2018 differed by the number of comorbidities in people with type 2 diabetes (T2DM). METHODS: A total of 120 409 adults with newly diagnosed T2DM between 2000 and 2018 were classified by the number of prevalent and incident comorbidities. Data on face-to-face and telephone primary care consultations with a nurse or physician were obtained. Crude and sex- and age-adjusted annual consultation rates and associated costs were calculated based on the number of comorbidities at the time of consultation. RESULTS: The crude rate of face-to-face primary care consultations for patients without comorbidities was 10.3 (95% confidence interval [CI] 10.3-10.4) per person-year, 12.7 (95% CI 12.7-12.7) for patients with one comorbidity, 15.1 (95% CI 15.1-15.2) for those with two comorbidities, and 18.7 (95% CI 18.7-18.8) for those with three or more comorbidities. The mean annual inflation-adjusted cost for face-to-face consultations was £412.70 per patient without comorbidities, £516.80 for one comorbidity, £620.75 for two comorbidities, and £778.83 for three or more comorbidities. The age- and sex-adjusted face-to-face consultation rate changed by an average of -3.3% (95% CI -4.4 to -2.3) per year from 2000 to 2018 for patients without comorbidities, -2.7% (95% CI -4.0 to -1.3) for those with one comorbidity, -2.2% (95% CI -3.3 to -1.2) for those with two comorbidities, and -4.3% (95% CI -8.7 to +0.3) for those with three or more comorbidities. CONCLUSIONS: Although consultation rates for all patients decreased from 2000 to 2018, there was a significant disparity between the rate for patients with and without comorbidities. Patients with T2DM and comorbidities may require different models of service delivery.
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    Effectiveness of the Transformation model, a model of care that integrates diabetes services across primary, secondary and community care: A retrospective study
    Brady, EM ; Bodicoat, DH ; Zaccardi, F ; Seidu, S ; Idris, I ; Khunti, K ; Farooqi, A ; Davies, MJ (WILEY, 2021-02-14)
    AIMS: The primary aim was to evaluate the effectiveness of a model integrating diabetes services across primary, secondary and community care (Transformation model). The secondary aim was to understand whether changes resulted from the model. METHODS: The model was implemented In Leicester, Leicestershire and Rutland (UK) across three clinical commissioning groups, the acute trust and accompanying stakeholders. One clinical commissioning group (Leicester City) implemented the entire model and was the primary evaluation population. A quasi-experimental interrupted time series design was employed. The primary outcome was number of Type 2 diabetes-related bed-days per 1000 patients. RESULTS: In the primary population, the mean number of Type 2 diabetes-related bed-days per 1000 patients was increasing before model implementation by 0.33/month (95% confidence interval: -0.07, 0.72), whereas it was decreasing after implementation by a mean value of -0.14/month (-0.33, 0.06); a statistically significant difference (p = 0.04). Secondary analyses showed: nationally, there was no significant change between the pre- and post-periods so it is unlikely that large secular change drove the improvement; the other two Leicestershire clinical commissioning groups saw improvement or stability; underlying processes worked as hypothesised overall; diabetes biomedical markers deteriorated in the primary care population suggesting a change in case-mix due to moving some patients out of secondary care. CONCLUSIONS: Given that the initial aim was to shift services from secondary to primary care without causing harm, an improvement is better than expected. This observational evaluation cannot show conclusively that improvements were due to the Transformation model, but secondary analyses support this.