Factors Associated with Length of Hospitalization in Diabetic Patients with Mild COVID-19: Experiences from a Tertiary University Center in Serbia (preprint)

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Diabetes knowledge, attitudes and practices among Chinese primary care physicians: A cross-sectional study (preprint)

Background: Type 2 diabetes mellitus (T2DM) is a public health crisis that requires adequate knowledge, attitudes, and practices (KAP) by health care providers to prevent or delay the progression of the disease. This study aimed to assess the KAP regarding T2DM among primary care providers (PCPs) in Central China.Methods: This multicenter cross-sectional study was conducted among 971 PCPs using self-administered KAP questionnaires. Questionnaires were designed to evaluate KAP regarding T2DM among PCPs, and was measured with SPSS software.Results: A total of 971 PCPs with a mean age of 44.0 ± 10.2 years were evaluated. 620 (63.9%) PCPs worked at village clinic and 605 (62.3%) PCPs have been working more than 20 years. Only 26.3% of the respondents participated in CME programs regarding diabetes in the past year due to Covid-19 pandemic. Overall, despite positive attitudes toward diabetes, there were substantial gaps in knowledge and practices. The PCPs scored 7.25 out of 14 points on the knowledge subscales, 7.13 out of 8 on the attitude subscales, and 4.85 out of 11 on the practice subscales. Gender, age, practice setting, professional titles, duration of practice and CME attendance were significant predictors of knowledge; Age, practice setting and duration of practice were significant predictors of attitudes; and family history of diabetes affected PCP practices.Conclusions: Despite positive attitudes toward diabetes, there were substantial gaps in knowledge and practices. These findings call for action from relevant health authorities and policy makers to improve PCPs' KAP regarding diabetes in Central China.

Cardioprotective effects of vaccination in hospitalized patients with COVID-19 (preprint)

Background COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. Aim The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. Methods In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Results Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen’s d: -0.52, 95% CI [-1.01; -0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Conclusion Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients.

Post-COVID-19 Condition Patients’ Utilisation of Healthcare Resources after Implementation of an Integrated Care Unit: A Retrospective and Case-Control Observational Study (preprint)

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

A moderately higher time-in-range threshold improves the prognosis of type-2 diabetes patients complicated with COVID-19 (preprint)

After fully lifting coronavirus disease 2019 (COVID-19) pandemic control measures in mainland China in 12/2022, the incidence of COVID-19 has increased markedly, making it difficult to meet the general time-in-range (TIR) requirement. We investigated a more clinically practical TIR threshold and examined its association with the prognosis of COVID-19 patients with type-2 diabetes. Sixty-three type-2 diabetes patients complicated with COVID-19 were evaluated. Patient information included epidemiological and laboratory characteristics, treatment options and outcomes. The percentages of time-above-range (TAR), time-below-range (TBR) and TIR were calculated from intermittently scanned continuous glucose monitoring. The composite end point included a >20-day length of stay, intensive care unit admission, mechanical ventilation use, or death. TIR with thresholds of 80 to 190 mg/dL was significantly associated with favorable outcomes. An increase of 1% in TIR is connected with a reduction of 3.70% in the risk of adverse outcomes. The Youden index was highest when the TIR was 54.73%, and the sensitivity and specificity were 58.30% and 77.80%, respectively. After accounting for confounding variables, our analysis revealed that threshold target ranges (TARs) ranging from 200 mg/dL to 230 mg/dL significantly augmented the likelihood of adverse outcomes.The TIR threshold of 80 to 190 mg/dL has a comparatively high predictive value of the prognosis of COVID-19. TIR >54.73% was associated with a decreased risk of adverse outcomes. These findings provide clinically critical insights into possible avenues to improve outcomes for COVID-19 patients with type-2 diabetes.

Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes (preprint)

Diabetes is associated with an increased risk of Coronavirus disease 2019 (COVID-19) vulnerability and mortality. COVID-19 vaccines significantly reduce the risks of serious COVID-19 outcomes, but the impact of COVID-19 vaccines including their effectiveness and adverse effects in patients with diabetes are not well known yet. Here, we showed that 61.1% patients with type 2 diabetes, but not healthy controls, exhibited aggravated insulin resistance towards the booster shots of the COVID-19 vaccine. Furthermore, we showed that COVID-19 vaccination once a week also impaired insulin sensitivity in healthy mice after four weeks. We further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice. This study suggests clinical implications for the close monitoring of glycemic control in diabetic patients after receiving COVID-19 vaccines and indicates the beneficial action of metformin in counteracting insulin signaling variations induced by COVID-19 vaccination in diabetic patients.

Diabetes related emergency department visits among adults during the COVID-19 pandemic - an analysis of data from the New York City syndromic surveillance system (preprint)

ObjectiveNew York City was an early epicenter of the COVID-19 pandemic. We aim to describe population level epidemiological trends in diabetes related emergency department (ED) visits among adults in New York City, for the period prior to and encompassing the first four waves of the pandemic. Research Design and MethodsWe used data from the New York City ED syndromic surveillance system during December 30, 2018 through May 21, 2022. This system captures all visits from EDs in the city in near-real time. We matched these visits to laboratory confirmed COVID-19 positivity data beginning with February 15, 2020. ResultsCompared to pre-pandemic baseline levels, diabetes related ED visits noticeably increased during the first wave in spring 2020, though this did not necessarily translate to net increases overall during that period. Visits for diabetic ketoacidosis, particularly among adults with type 2 diabetes, sharply increased before returning to pre-pandemic levels, most notably during wave 1 and wave 4 in winter 2021-2022. Trajectories of diabetes-related ED visits differed by diabetes type, age, and sex. Some ED visit trends did not return to pre-pandemic baseline levels. ConclusionsThe COVID-19 pandemic, especially the first wave in the spring of 2020, coincided with a dramatic shift in diabetes related ED utilization in New York City. Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics. A robust syndromic surveillance system that includes infectious and non-infectious syndromes is useful to better prepare, mitigate, and respond to population-level events. Article HighlightsO_LIDiabetes related emergency department (ED) visits in New York City increased dramatically with the emergence of the COVID-19 pandemic in spring 2020. C_LIO_LIThe trajectory of diabetes-related ED visits differed by diabetes type, age, sex, and pandemic wave. C_LIO_LIThe diabetes complication of diabetic ketoacidosis among adults with type 2 diabetes showed sharp increases in the first and fourth waves of the pandemic, respectively its initial emergence in spring 2020 and the Omicron variant in winter 2021-2022. C_LIO_LIOur findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics. C_LI SummaryData from NYCs syndromic surveillance system showed major increases in #type2diabetes complications (e.g. diabetic ketoacidosis) during #COVID-19 waves 1 and 4 (Omicron) - this tool may be useful for population-level monitoring of chronic disease complications during emergencies

Weight trends amongst adults with diabetes or hypertension during the COVID-19 pandemic: an observational study using OpenSAFELY (preprint)

AimsTo describe patterns of weight change amongst adults living in England with Type 2 Diabetes (T2D) and/or hypertension during the COVID-19 pandemic. Design and SettingWith the approval of NHS England, we conducted an observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP. MethodWe estimated individual rates of weight gain during the pandemic ({delta}). We then estimated associations between clinical and sociodemographic characteristics and rapid weight gain (>0.5kg/m2/year) using multivariable logistic regression. ResultsWe extracted data on adults with T2D (n=1,231,455, 44% female, 76% white British) or hypertension (n=3,558,405, 50% female, 84% white British). Adults with T2D lost weight overall (median {delta} = -0.1kg/m2/year [IQR: -0.7, 0.4]), however, rapid weight gain was common (20.7%) and associated with sex (male vs female: aOR 0.78[95%CI 0.77, 0.79]); age, older age reduced odds (e.g. 60-69-year-olds vs 18-29-year-olds: aOR 0.66[0.61, 0.71]); deprivation, (least-deprived-IMD vs most-deprived-IMD: aOR 0.87[0.85, 0.89]); white ethnicity (Black vs White: aOR 0.70[0.69, 0.71]); mental health conditions (e.g. depression: aOR 1.13 [1.12, 1.15]); and diabetes treatment (non-insulin treatment vs no pharmacological treatment: aOR 0.68[0.67, 0.69]). Adults with hypertension maintained stable weight overall (median {delta} = 0.0kg/m2/year [-0.6, 0.5]), however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D. ConclusionAmongst adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common amongst females, younger adults, those living in more deprived areas, and those with mental health conditions. How this fits inPrevious studies, in the general population, have reported female sex, deprivation and comorbid mental health conditions increased risk of unhealthy weight gain during the pandemic, but it is not clear whether people living with hypertensions and/or type 2 diabetes experienced the same trends. We found that, during the pandemic, adults with hypertension maintained a stable weight whilst those with type 2 diabetes lost weight overall. However, underlying these overall trends, rapid weight gain was common amongst people with type 2 diabetes (20.7%) or hypertension (24.7%)), with female sex, younger age, deprivation, and comorbid mental health conditions associated with an increased odds of rapid weight gain in both populations. We have identified clinical and sociodemographic characteristics of individuals with hypertension and/or type 2 diabetes who could benefit from primary care interventions on weight and health behaviours to combat health inequalities in patterns of weight gain that were exacerbated by the pandemic.

Visceral adipose macrophage content does not associate with body mass index or systemic inflammation in COVID-19: an autopsy study (preprint)

Introduction: Adiposity, especially visceral adiposity with elevated body mass index (BMI), is associated with a hyperinflammatory syndrome and poor outcomes in patients with COVID-19. In other diseases such as obesity, type 2 diabetes, and rheumatoid arthritis, systemic inflammation is driven directly by visceral adipose macrophages which release pro-inflammatory cytokines. Currently it is unknown whether visceral adipose tissue macrophage content may similarly explain the observation that COVID-19 patients with elevated BMI are at risk for a hyperinflammatory syndrome and death. Methods: This was a retrospective study of hospitalized adults who died of COVID-19 between March 2020 and June 2020 and underwent autopsy. Visceral adipose tissue macrophage content was quantified by histological staining of visceral adipose tissue samples with CD68, using pericolic fat gathered at autopsy from each subject. Clinical data including inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive Protein (CRP), Troponin, D-dimer, Interleukin-6 (IL-6), and ferritin as well as BMI were collected from electronic medical records. Results: A total of 39 subjects were included in this study. There was no association between BMI and visceral adipose tissue macrophage content (Spearman R=0.025, p=0.88). Additionally, there was no association between adipose tissue macrophage content and any of the systemic markers of inflammation measured including ESR, CRP, Troponin, D-dimer, IL-6, and Ferritin (p>0.05 for all markers). Conclusion: Unlike chronic diseases such as obesity, type 2 diabetes, and rheumatoid arthritis, elevated BMI is not associated with increased visceral adipose tissue macrophage content in patients who died of COVID-19. Additionally, among patients who died of COVID-19, visceral adipose tissue macrophage content is not associated with markers of systemic inflammation. These results suggest that the elevations in systemic markers of inflammation-and the hyperinflammatory syndrome often observed during acute COVID-19-does not directly originate from visceral adipose macrophages as it seems to in chronic disease states.

Association of polypharmacy and burden of comorbidities on COVID-19 adverse outcomes in people with type 1 or type 2 diabetes (preprint)

Aim: To investigate whether polypharmacy and comorbidities conveyed more risk of adverse health outcomes following COVID-19 infection in people with type 1 diabetes (T1DM) or type 2 diabetes (T2DM). Materials and methods: The Greater Manchester Care Record (GMCR) is an integrated database of electronic health records containing data collected from 433 general practices in Greater Manchester. Baseline demographic information (age, BMI, gender, ethnicity, smoking status, deprivation index), hospital admission or death within 28 days of infection were extracted for adults (18+) diagnosed with either T1DM or T2DM. Results: For T2DM, 16 to 20 medications (p=0.01; OR [95% CI]=2.37 [1.31 to 4.32]) and > 20 medications (p=0; OR [95% CI]=3.14 [1.75 to 5.62]) were associated with increased risk of death following COVID-19 infection. Increased risk of hospital admissions in T2DM individuals was determined for 11 to 15 medications (p=0.01; OR [95% CI]=1.34 [1.06 to 1.69]) and above. This was independent of comorbidities, metabolic and demographic factors. For T1DM there was no association of polypharmacy with hospital admission. Respiratory, cardiovascular/cerebrovascular and gastrointestinal conditions were associated with increased risk of hospital admissions and deaths in T2DM (p>0.001). Conclusion: We have shown in T2DM an independent association of number of medications taken from 11 upwards with adverse health consequences following COVID-19 infection. We also found that individuals with diabetes develop comorbidities that were common across both T1DM and T2DM. This study has laid the foundation for future investigations into the way that complex pharmacological interactions may influence clinical outcomes in people with T2DM.

National Changes in Diabetes Care Practices during the COVID-19 Pandemic: Prospective Study of US Adults (preprint)

Background There is a lack of nationally representative prospective data on the impact of the COVID-19 pandemic on diabetes care and management in adults with type 2 diabetes. We examined changes in diabetes care and management practices before and after the onset of the COVID-19 pandemic. Methods Using the National Health Interview Survey, we analyzed data from 870 adults living with type 2 diabetes who were interviewed in 2019 and re-interviewed between August and December 2020. Exposure to the COVID-19 pandemic was defined by year of survey (2019, pre-pandemic; 2020, pandemic). We estimated percent change in past year blood sugar check by a health professional and current use of blood sugar lowering medication overall and by sociodemographic subgroups. Results Receiving an annual blood sugar test fell by -3.3 percentage points (pp) (95% CI -5.7, -1.0), from 98.3% in 2019 to 95.0% in late 2020. The reduction in annual blood glucose testing was largely consistent across socio-demographic groups and was particularly pronounced among adults not working and adults aged 65 years and older. In the same time period, current use of diabetes medications increased by +3.8 pp (0.7, 6.9), from 85.9% to 89.7%. The increase in medication use was most pronounced among individuals aged 40-64-year old, employed, and those living in large central metropolitan areas. Conclusions Nationally, adults with Type 2 diabetes reported a reduction in annual blood glucose testing by a health professional and an increase in diabetes medication usage during the COVID-19 pandemic. If sustained after the end of the COVID-19 public health emergency, these changes have implications for national diabetes management and care.

Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people. (preprint)

Background Type 2 diabetes (T2DM) incidence is increased after diagnosis of COVID-19. The impact of vaccination on this increase, for how long it persists, and the effect of COVID-19 on other types of diabetes remain unclear. Methods With NHS England approval, we studied diabetes incidence following COVID-19 diagnosis in pre-vaccination (N=15,211,471, January 2020-December 2021), vaccinated (N =11,822,640), and unvaccinated (N=2,851,183) cohorts (June-December 2021), using linked electronic health records. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence post-COVID-19 diagnosis with incidence before or without diagnosis up to 102 weeks post-diagnosis. Results were stratified by COVID-19 severity (hospitalised/non-hospitalised) and diabetes type. Findings In the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 3.01 (95% CI: 2.76,3.28) in weeks 1-4 to 1.24 (1.12,1.38) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (4.86 (3.69,6.41)) versus 1.42 (1.24,1.62) in weeks 1-4) and for hospitalised COVID-19 (pre-vaccination cohort 21.1 (18.8,23.7) in weeks 1-4 declining to 2.04 (1.65,2.51) in weeks 52-102), than non-hospitalised COVID-19 (1.45 (1.27,1.64) in weeks 1-4, 1.10 (0.98,1.23) in weeks 52-102). T2DM persisted for 4 months after COVID-19 for ~73% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond a year post-COVID-19. Interpretation Elevated T2DM incidence after COVID-19 is greater, and persists longer, in hospitalised than non-hospitalised people. It is markedly less apparent post-vaccination. Testing for T2DM after severe COVID-19 and promotion of vaccination are important tools in addressing this public health problem.

Metformin - a new approach.

Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.

A culturally tailored personaliseD nutrition intErvention in South ASIan women at risk of Gestational Diabetes Mellitus (DESI-GDM): a randomised controlled trial protocol.

INTRODUCTION: South Asians are more likely to develop gestational diabetes mellitus (GDM) than white Europeans. Diet and lifestyle modifications may prevent GDM and reduce undesirable outcomes in both the mother and offspring. Our study seeks to evaluate the effectiveness and participant acceptability of a culturally tailored, personalised nutrition intervention on the glucose area under the curve (AUC) after a 2-hour 75 g oral glucose tolerance test (OGTT) in pregnant women of South Asian ancestry with GDM risk factors. METHODS AND ANALYSIS: A total of 190 South Asian pregnant women with at least 2 of the following GDM risk factors-prepregnancy body mass index>23, age>29, poor-quality diet, family history of type 2 diabetes in a first-degree relative or GDM in a previous pregnancy will be enrolled during gestational weeks 12-18, and randomly assigned in a 1:1 ratio to: (1) usual care, plus weekly text messages to encourage walking and paper handouts or (2) a personalised nutrition plan developed and delivered by a culturally congruent dietitian and health coach; and FitBit to track steps. The intervention lasts 6-16 weeks, depending on week of recruitment. The primary outcome is the glucose AUC from a three-sample 75 g OGTT 24-28 weeks' gestation. The secondary outcome is GDM diagnosis, based on Born-in-Bradford criteria (fasting glucose>5.2 mmol/L or 2 hours post load>7.2 mmol/L). ETHICS AND DISSEMINATION: The study has been approved by the Hamilton Integrated Research Ethics Board (HiREB #10942). Findings will be disseminated among academics and policy-makers through scientific publications along with community-orientated strategies. TRIAL REGISTRATION NUMBER: NCT03607799.

Effects of COVID-19 pandemic lockdown on the metabolic control of type 2 diabetes mellitus in patients.

Objective: The effects of the COVID-19 pandemic on the control of diabetes mellitus in patients are largely unknown. In this study we aimed to analyze the impact of the pandemic and the ensuing lockdown on the management of type 2 diabetes mellitus. Subjects and methods: A total of 7,321patients with type 2 diabetes mellitus (4,501 from the pre-pandemic period, 2,820 from the post-pandemic period) were studied retrospectively. Results: The admission of patients with diabetes melitus (DM) decreased significantly during the pandemic (4,501 pre-pandemic vs. 2,820 post-pandemic; p < 0.001). The mean age of patients was statistically lower (51.5 ± 14.0 vs. 49.7 ± 14.5 years; p < 0.001), and the mean glycated hemoglobin (A1c) level was significantly higher (7.9% ± 2.4% vs. 7.3% ± 1.7%; p < 0.001) in the post-pandemic period than in the pre-pandemic. The female/male ratio was similar in both periods (59.9%/40.1% for pre-pandemic, 58.6%/41.4% for post-pandemic; p = 0.304). As calculated by month the pre-pandemic rate of women was higher only in January (53.1% vs. 60.6%, p = 0.02). Mean A1c levels were higher in the postpandemic period than in the same month of the previous year, excluding July and October (p = 0.001 for November, p < 0.001 for others). Postpandemic patients admitted to the outpatient clinic were significantly younger than prepandemic visits for July (p = 0.001), August (p < 0.001) and December (p < 0.001). Conclusion: The lockdown had detrimental effects on blood sugar management in patients with DM. Hence, diet and exercise programs should be adapted to home conditions, and social and psychological support should be provided to patients with DM.

XRRmeta: Exact Inference for Random-Effects Meta-Analyses with Rare Events (preprint)

Meta-analysis aggregates information across related studies to provide more reliable statistical inference and has been a vital tool for assessing the safety and efficacy of many high profile pharmaceutical products. A key challenge in conducting a meta-analysis is that the number of related studies is typically small. Applying classical methods that are asymptotic in the number of studies can compromise the validity of inference, particularly when heterogeneity across studies is present. Moreover, serious adverse events are often rare and can result in one or more studies with no events in at least one study arm. While it is common to use arbitrary continuity corrections or remove zero-event studies to stabilize or define effect estimates in such settings, these practices can invalidate subsequent inference. To address these significant practical issues, we introduce an exact inference method for comparing event rates in two treatment arms under a random effects framework, which we coin "XRRmeta". In contrast to existing methods, the coverage of the confidence interval from XRRmeta is guaranteed to be at or above the nominal level (up to Monte Carlo error) when the event rates, number of studies, and/or the within-study sample sizes are small. XRRmeta is also justified in its treatment of zero-event studies through a conditional inference argument. Importantly, our extensive numerical studies indicate that XRRmeta does not yield overly conservative inference. We apply our proposed method to reanalyze the occurrence of major adverse cardiovascular events among type II diabetics treated with rosiglitazone and in a more recent example examining the utility of face masks in preventing person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19).

COVID-19 Vaccination and Clinical Outcomes at a Secondary Referral Hospital During the Delta Variant-dominant Period in West Sumatra, Indonesia.

OBJECTIVES: The second wave of coronavirus disease 2019 (COVID-19) cases in Indonesia, during which the Delta variant predominated, took place after a vaccination program had been initiated in the country. This study was conducted to assess the impact of COVID-19 vaccination on unfavorable clinical outcomes including hospitalization, severe COVID-19, intensive care unit (ICU) admission, and death using a real-world model. METHODS: This single-center retrospective cohort study involved patients with COVID-19 aged ≥18 years who presented to the COVID-19 emergency room at a secondary referral teaching hospital between June 1, 2021 and August 31, 2021. We used a binary logistic regression model to assess the effect of COVID-19 vaccination on unfavorable clinical outcomes, with age, sex, and comorbidities as confounding variables. RESULTS: A total of 716 patients were included, 32.1% of whom were vaccinated. The elderly participants (≥65 years) had the lowest vaccine coverage among age groups. Vaccination had an effectiveness of 50% (95% confidence interval [CI], 25 to 66) for preventing hospitalization, 97% (95% CI, 77 to 99) for preventing severe COVID-19, 95% (95% CI, 56 to 99) for preventing ICU admission, and 90% (95% CI, 22 to 99) for preventing death. Interestingly, patients with type 2 diabetes had a 2-fold to 4-fold elevated risk of unfavorable outcomes. CONCLUSIONS: Among adults, COVID-19 vaccination has a moderate preventive impact on hospitalization but a high preventive impact on severe COVID-19, ICU admission, and death. The authors suggest that relevant parties increase COVID-19 vaccination coverage, especially in the elderly population.

Impact of a social prescribing intervention in North East England on adults with type 2 diabetes: the SPRING_NE multimethod study.

Background: Link worker social prescribing enables health-care professionals to address patients' non-medical needs by linking patients into various services. Evidence for its effectiveness and how it is experienced by link workers and clients is lacking. Objectives: To evaluate the impact and costs of a link worker social prescribing intervention on health and health-care costs and utilisation and to observe link worker delivery and patient engagement. Data sources: Quality Outcomes Framework and Secondary Services Use data. Design: Multimethods comprising (1) quasi-experimental evaluation of effects of social prescribing on health and health-care use, (2) cost-effectiveness analysis, (3) ethnographic methods to explore intervention delivery and receipt, and (4) a supplementary interview study examining intervention impact during the first UK COVID-19 lockdown (April-July 2020). Study population and setting: Community-dwelling adults aged 40-74 years with type 2 diabetes and link workers in a socioeconomically deprived locality of North East England, UK. Intervention: Link worker social prescribing to improve health and well-being-related outcomes among people with long-term conditions. Participants: (1) Health outcomes study, approximately n = 8400 patients; EuroQol-5 Dimensions, five-level version (EQ-5D-5L), study, n = 694 (baseline) and n = 474 (follow-up); (2) ethnography, n = 20 link workers and n = 19 clients; and COVID-19 interviews, n = 14 staff and n = 44 clients. Main outcome measures: The main outcome measures were glycated haemoglobin level (HbA1c; primary outcome), body mass index, blood pressure, cholesterol level, smoking status, health-care costs and utilisation, and EQ-5D-5L score. Results: Intention-to-treat analysis of approximately 8400 patients in 13 intervention and 11 control general practices demonstrated a statistically significant, although not clinically significant, difference in HbA1c level (-1.11 mmol/mol) and a non-statistically significant 1.5-percentage-point reduction in the probability of having high blood pressure, but no statistically significant effects on other outcomes. Health-care cost estimates ranged from £18.22 (individuals with one extra comorbidity) to -£50.35 (individuals with no extra comorbidity). A statistically non-significant shift from unplanned (non-elective and accident and emergency admissions) to planned care (elective and outpatient care) was observed. Subgroup analysis showed more benefit for individuals living in more deprived areas, for the ethnically white and those with fewer comorbidities. The mean cost of the intervention itself was £1345 per participant; the incremental mean health gain was 0.004 quality-adjusted life-years (95% confidence interval -0.022 to 0.029 quality-adjusted life-years); and the incremental cost-effectiveness ratio was £327,250 per quality-adjusted life-year gained. Ethnographic data showed that successfully embedded, holistic social prescribing providing supported linking to navigate social determinants of health was challenging to deliver, but could offer opportunities for improving health and well-being. However, the intervention was heterogeneous and was shaped in unanticipated ways by the delivery context. Pressures to generate referrals and meet targets detracted from face-to-face contact and capacity to address setbacks among those with complex health and social problems. Limitations: The limitations of the study include (1) a reduced sample size because of non-participation of seven general practices; (2) incompleteness and unreliability of some of the Quality and Outcomes Framework data; (3) unavailability of accurate data on intervention intensity and patient comorbidity; (4) reliance on an exploratory analysis with significant sensitivity analysis; and (5) limited perspectives from voluntary, community and social enterprise. Conclusions: This social prescribing model resulted in a small improvement in glycaemic control. Outcome effects varied across different groups and the experience of social prescribing differed depending on client circumstances. Future work: To examine how the NHS Primary Care Network social prescribing is being operationalised; its impact on health outcomes, service use and costs; and its tailoring to different contexts. Trial registration: This trial is registered as ISRCTN13880272. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme, Community Groups and Health Promotion (grant no. 16/122/33) and will be published in full in Public Health Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

Social prescribing happens when health-care staff refer patients to a link worker. Link workers support and help patients to access community services to improve their health and well-being. Social prescribing is popular within the NHS, but there is little evidence that it works. We looked at a social prescribing model being delivered in a disadvantaged area in north-east England.