Promoting inclusion in clinical trials-a rapid review of the literature and recommendations for action.

BACKGROUND: Without inclusion of diverse research participants, it is challenging to understand how study findings will translate into the real world. Despite this, a lack of inclusion of those from under-served groups in research is a prevailing problem due to multi-faceted barriers acting at multiple levels. Therefore, we rapidly reviewed international published literature, in relation to clinical trials, on barriers relating to inclusion, and evidence of approaches that are effective in overcoming these. METHODS: A rapid literature review was conducted searching PubMed for peer-reviewed articles that discussed barriers to inclusion or strategies to improve inclusion in clinical trial research published between 2010 and 2021. Grey literature articles were excluded. RESULTS: Seventy-two eligible articles were included. The main barriers identified were language and communication, lack of trust, access to trials, eligibility criteria, attitudes and beliefs, lack of knowledge around clinical trials, and logistical and practical issues. In relation to evidence-based strategies and enablers, two key themes arose: [1] a multi-faceted approach is essential [2]; no single strategy was universally effective either within or between trials. The key evidence-based strategies identified were cultural competency training, community partnerships, personalised approach, multilingual materials and staff, communication-specific strategies, increasing understanding and trust, and tackling logistical barriers. CONCLUSIONS: Many of the barriers relating to inclusion are the same as those that impact trial design and healthcare delivery generally. However, the presentation of these barriers among different under-served groups may be unique to each population's particular circumstances, background, and needs. Based on the literature, we make 15 recommendations that, if implemented, may help improve inclusion within clinical trials and clinical research more generally. The three main recommendations include improving cultural competency and sensitivity of all clinical trial staff through training and ongoing personal development, the need to establish a diverse community advisory panel for ongoing input into the research process, and increasing recruitment of staff from under-served groups. Implementation of these recommendations may help improve representation of under-served groups in clinical trials which would improve the external validity of associated findings.

COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.

BACKGROUND: Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities. METHODS: We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals. CONCLUSIONS: Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).

Type 2 diabetes.

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.

'Self-Management Intervention through Lifestyle Education for Kidney health' (the SMILE-K study): protocol for a single-blind longitudinal randomised controlled trial with nested pilot study.

INTRODUCTION: Many people living with chronic kidney disease (CKD) are expected to self-manage their condition. Patient activation is the term given to describe the knowledge, skills and confidence a person has in managing their own health and is closely related to the engagement in preventive health behaviours. Self-management interventions have the potential to improve remote disease management and health outcomes. We are testing an evidence-based and theory-based digital self-management structured 10-week programme developed for peoples with CKD called 'My Kidneys & Me'. The primary aim of the study (Self-Management Intervention through Lifestyle Education for Kidney health (SMILE-K)) is to assess the effect on patient activation levels. METHODS AND ANALYSIS: A single-blind randomised controlled trial (RCT) with a nested pilot study will assess the feasibility of the intervention and study design before continuation to a full RCT. Individuals aged 18 years or older, with established CKD stage 3-4 (eGFR of 15-59 mL/min/1.73 m2) will be recruited through both primary and secondary care pathways. Participants will be randomised into two groups: intervention group (receive My Kidneys & Me in addition to usual care) and control group (usual care). The primary outcome of the nested pilot study is feasibility and the primary outcome of the full RCT is the Patient Activation Measu (PAM-13). The full RCT will assess the effect of the programme on online self-reported outcomes which will be assessed at baseline, after 10 weeks, and then after 20 weeks in both groups. A total sample size of N=432 participants are required based on a 2:1 randomisation. A substudy will measure physiological changes (eg, muscle mass, physical function) and patient experience (qualitative semi-structured interviews). ETHICS AND DISSEMINATION: This study was fully approved by the Research Ethics Committee-Leicester South on the 19 November 2020 (reference: 17/EM/0357). All participants are required to provide informed consent obtained online. The results are expected to be published in scientific journals and presented at clinical research conferences. This is protocol version 1.0 dated 27 January 2021. TRIAL REGISTRATION NUMBER: ISRCTN18314195.

Effectiveness of an intervention for reducing sitting time and improving health in office workers: three arm cluster randomised controlled trial.

OBJECTIVES: To evaluate the effectiveness of an intervention, with and without a height adjustable desk, on daily sitting time, and to investigate the relative effectiveness of the two interventions, and the effectiveness of both interventions on physical behaviours and physical, biochemical, psychological, and work related health and performance outcomes. DESIGN: Cluster three arm randomised controlled trial with follow-up at three and 12 months. SETTING: Local government councils in Leicester, Liverpool, and Greater Manchester, UK. PARTICIPANTS: 78 clusters including 756 desk based employees in defined offices, departments, or teams from two councils in Leicester, three in Greater Manchester, and one in Liverpool. INTERVENTIONS: Clusters were randomised to one of three conditions: the SMART Work and Life (SWAL) intervention, the SWAL intervention with a height adjustable desk (SWAL plus desk), or control (usual practice). MAIN OUTCOMES MEASURES: The primary outcome measure was daily sitting time, assessed by accelerometry, at 12 month follow-up. Secondary outcomes were accelerometer assessed sitting, prolonged sitting, standing and stepping time, and physical activity calculated over any valid day, work hours, workdays, and non-workdays, self-reported lifestyle behaviours, musculoskeletal problems, cardiometabolic health markers, work related health and performance, fatigue, and psychological measures. RESULTS: Mean age of participants was 44.7 years, 72.4% (n=547) were women, and 74.9% (n=566) were white. Daily sitting time at 12 months was significantly lower in the intervention groups (SWAL -22.2 min/day, 95% confidence interval -38.8 to -5.7 min/day, P=0.003; SWAL plus desk -63.7 min/day, -80.1 to -47.4 min/day, P<0.001) compared with the control group. The SWAL plus desk intervention was found to be more effective than SWAL at changing sitting time (-41.7 min/day, -56.3 to -27.0 min/day, P<0.001). Favourable differences in sitting and prolonged sitting time at three and 12 month follow-ups for both intervention groups and for standing time for the SWAL plus desk group were observed during work hours and on workdays. Both intervention groups were associated with small improvements in stress, wellbeing, and vigour, and the SWAL plus desk group was associated with improvements in pain in the lower extremity, social norms for sitting and standing at work, and support. CONCLUSIONS: Both SWAL and SWAL plus desk were associated with a reduction in sitting time, although the addition of a height adjustable desk was found to be threefold more effective. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11618007.

Cultural adaptation of a diabetes self-management education and support (DSMES) programme for two low resource urban settings in Ghana, during the COVID-19 era.

BACKGROUND: Type 2 diabetes is a significant public health problem globally and associated with significant morbidity and mortality. Diabetes self-management education and support (DSMES) programmes are associated with improved psychological and clinical outcomes. There are currently no structured DSMES available in Ghana. We sought to adapt an evidence-based DSMES intervention for the Ghanaian population in collaboration with the local Ghanaian people. METHODS: We used virtual engagements with UK-based DSMES trainers, produced locally culturally and linguistically appropriate content and modified the logistics needed for the delivery of the self-management programme to suit people with low literacy and low health literacy levels. CONCLUSIONS: A respectful understanding of the socio-cultural belief systems in Ghana as well as the peculiar challenges of low resources settings and low health literacy is necessary for adaptation of any DSMES programme for Ghana. We identified key cultural, linguistic, and logistic considerations to incorporate into a DSMES programme for Ghanaians, guided by the Ecological Validity Model. These insights can be used further to scale up availability of structured DSMES in Ghana and other low- middle- income countries.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

The impact of obesity on severe disease and mortality in people with SARS-CoV-2: A systematic review and meta-analysis.

Background: Obesity accompanied by excess ectopic fat storage has been postulated as a risk factor for severe disease in people with SARS-CoV-2 through the stimulation of inflammation, functional immunologic deficit and a pro-thrombotic disseminated intravascular coagulation with associated high rates of venous thromboembolism. Methods: Observational studies in COVID-19 patients reporting data on raised body mass index at admission and associated clinical outcomes were identified from MEDLINE, Embase, Web of Science and the Cochrane Library up to 16 May 2020. Mean differences and relative risks (RR) with 95% confidence intervals (CIs) were aggregated using random effects models. Results: Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible. Comparing BMI ≥ 25 vs <25 kg/m2, the RRs (95% CIs) of severe illness and mortality were 2.35 (1.43-3.86) and 3.52 (1.32-9.42), respectively. In a pooled analysis of three studies, the RR (95% CI) of severe illness comparing BMI > 35 vs <25 kg/m2 was 7.04 (2.72-18.20). High levels of statistical heterogeneity were partly explained by age; BMI ≥ 25 kg/m2 was associated with an increased risk of severe illness in older age groups (≥60 years), whereas the association was weaker in younger age groups (<60 years). Conclusions: Excess adiposity is a risk factor for severe disease and mortality in people with SARS-CoV-2 infection. This was particularly pronounced in people 60 and older. The increased risk of worse outcomes from SARS-CoV-2 infection in people with excess adiposity should be taken into account when considering individual and population risks and when deciding on which groups to target for public health messaging on prevention and detection measures. Systematic review registration: PROSPERO 2020: CRD42020179783.

Physical activity and sedentary behaviour interventions for people living with both frailty and multiple long-term conditions: a scoping review protocol

IntroductionThe number of people living with multiple long-term conditions (MLTCs) is predicted to rise. Within this population, those also living with frailty are particularly vulnerable to poor outcomes, including decreased function. Increased physical activity, including exercise, has the potential to improve function in those living with both MLTCs and frailty but, to date, the focus has remained on older people and may not reflect outcomes for the growing number of younger people living with MLTCs and frailty. For those with higher burdens of frailty and MLTCs, physical activity may be challenging. Tailoring physical activity in response to symptoms and periods of ill-health, involving family and reducing sedentary behaviour may be important in this population. How the tailoring of interventions has been approached within existing studies is currently unclear. This scoping review aims to map the available evidence regarding these interventions in people living with both frailty and MLTCs.Methods and analysisWe will use a six-stage process: (1) identifying the research questions;(2) identifying relevant studies (via database searches);(3) selecting studies;(4) charting the data;(5) collating and summarising and (6) stakeholder consultation. Studies will be critically appraised using the Mixed Methods Appraisal Tool.Ethics and disseminationAll data in this project will be gathered through database searches. Stakeholder consultation will be undertaken with an established patient and public involvement group. We will disseminate our findings via social media, publication and engagement meetings.

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.

Association between household size and COVID-19: A UK Biobank observational study.

OBJECTIVE: To assess the association between household size and risk of non-severe or severe COVID-19. DESIGN: A longitudinal observational study. SETTING: This study utilised UK Biobank linked to national SARS-CoV-2 laboratory test data. PARTICIPANTS: 401,910 individuals with available data on household size in UK Biobank. MAIN OUTCOME MEASURES: Household size was categorised as single occupancy, two-person households and households of three or more. Severe COVID-19 was defined as a positive SARS-CoV-2 test on hospital admission or death with COVID-19 recorded as the underlying cause; and non-severe COVID-19 as a positive test from a community setting. Logistic regression models were fitted to assess associations, adjusting for potential confounders. RESULTS: Of 401,910 individuals, 3612 (1%) were identified as having suffered from a severe COVID-19 infection and 11,264 (2.8%) from a non-severe infection, between 16 March 2020 and 16 March 2021. Overall, the odds of severe COVID-19 was significantly higher among individuals living alone (adjusted odds ratio: 1.24 [95% confidence interval: 1.14 to 1.36], or living in a household of three or more individuals (adjusted odds ratio: 1.28 [1.17 to 1.39], when compared to individuals living in a household of two. For non-severe COVID-19 infection, individuals living in a single-occupancy household had lower odds compared to those living in a household of two (adjusted odds ratio: 0.88 [0.82 to 0.93]. CONCLUSIONS: Odds of severe or non-severe COVID-19 infection were associated with household size. Increasing understanding of why certain households are more at risk is important for limiting spread of the infection.

A population-based cohort study of obesity, ethnicity and COVID-19 mortality in 12.6 million adults in England.

Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in Black, South Asian and other ethnic minority groups, respectively.

Ethnic minorities and COVID-19: examining whether excess risk is mediated through deprivation.

BACKGROUND: People from South Asian and black minority ethnic groups are disproportionately affected by the COVID-19 pandemic. It is unknown whether deprivation mediates this excess ethnic risk. METHODS: We used UK Biobank with linked COVID-19 outcomes occurring between 16th March 2020 and 24th August 2020. A four-way decomposition mediation analysis was used to model the extent to which the excess risk of testing positive, severe disease and mortality for COVID-19 in South Asian and black individuals, relative to white individuals, would be eliminated if levels of high material deprivation were reduced within the population. RESULTS: We included 15 044 (53.0% women) South Asian and black and 392 786 (55.2% women) white individuals. There were 151 (1.0%) positive tests, 91 (0.6%) severe cases and 31 (0.2%) deaths due to COVID-19 in South Asian and black individuals compared with 1471 (0.4%), 895 (0.2%) and 313 (0.1%), respectively, in white individuals. Compared with white individuals, the relative risk of testing positive for COVID-19, developing severe disease and COVID-19 mortality in South Asian and black individuals were 2.73 (95% CI: 2.26, 3.19), 2.96 (2.31, 3.61) and 4.04 (2.54, 5.55), respectively. A hypothetical intervention moving the 25% most deprived in the population out of deprivation was modelled to eliminate between 40 and 50% of the excess risk of all COVID-19 outcomes in South Asian and black populations, whereas moving the 50% most deprived out of deprivation would eliminate over 80% of the excess risk of COVID-19 outcomes. CONCLUSIONS: The excess risk of COVID-19 outcomes in South Asian and black communities could be substantially reduced with population level policies targeting material deprivation.

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.

OBJECTIVE: Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death. METHODS: A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death. RESULTS: Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication. CONCLUSIONS: In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.

COVID-19 vaccine uptake and hesitancy opinions from frontline health care and social care workers: Survey data from 37 countries.

BACKGROUND AND AIMS: Vaccine hesitancy is an ongoing major challenge. We aimed to assess the uptake and hesitancy of the COVID-19 vaccination. METHODS: A short online survey was posted between April 12 to July 31, 2021 targeted at health and social care workers (HCWs) across the globe. RESULTS: 275 from 37 countries responded. Most were hospital or primary care physicians or nurses, 59% women, aged 18-60 years, and 21% had chronic conditions with most prevalent being diabetes, hypertension, and asthma. We found that most HCWs (93%) had taken or willing to receive the COVID-19 vaccine. While 7% were vaccine hesitant (mainly women aged 30-39 years), respondents main concerns was the safety or potential side effects. Vaccine willing respondents raised concerns of unequal access to the COVID-19 vaccination in some countries, and highlighted that the only solution to overcoming COVID-19 infections was the vaccine booster doses given annually and free mass vaccination. CONCLUSIONS: This study found that the majority of the frontline HCWs are willing to receive the COVID-19 vaccine. Further promotion of the COVID-19 vaccine would reassure and persuade HCWs to become vaccinated.

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

BACKGROUND: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection. METHODS: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein. RESULTS: Among 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]). CONCLUSION: The multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment.

Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

BACKGROUND: Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched. METHODS: We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories. RESULTS: The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50-69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease. CONCLUSION: Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making.