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The impact of global diabetes prevention efforts has been modest despite the promise of landmark diabetes prevention trials nearly twenty years ago. While national and regional initiatives show potential, challenges remain to adapt large-scale strategies in the real-world that fits individuals and their communities. Additionally, the sedentary lifestyle changes during the COVID-19 pandemic and guidelines that now call for earlier screening (e.g., US Preventative Task Force) will increase the pool of eligible adults worldwide. Thus, a more adaptable, person-centered approach that expands the current toolkit is urgently needed to innovate and revitalize our approach to diabetes prevention. This review identifies key priorities to optimize the population-level delivery of diabetes prevention based on a consensus-based evaluation of the current evidence among experts in global translational programs; key priorities identified include (1) participant eligibility, (2) intervention intensity, (3) delivery components, (4) behavioral economics, (5) technology, and (6) the role of pharmacotherapy. We offer a conceptual framework for a broader, person-centered approach to better address an individual’s risk, readiness, barriers, and digital competency.

There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes.The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbABetween Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose.Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India.Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

We examined changes in the prevalence of elevated depressive symptoms among US adults with diabetes, prediabetes, and normal glycemic status during 2005-2016.We analyzed data from 32,676 adults in the 2005-2016 National Health and Nutrition Examination Surveys. We defined diabetes as self-reporting a physician diagnosis of diabetes or A1C ≥ 6.5% [48 mmol/mol], and prediabetes as A1C 5.7-6.4% [39-46 mmol/mol]. We used the 9-item Patient Health Questionnaire (PHQ-9) score ≥ 10 or antidepressant use to define 'clinically significant depressive symptoms' (CSDS) and PHQ-9 score ≥ 12 as 'Major Depressive Disorder' (MDD). We calculated prevalence age-standardized to the 2000 US census and used logistic-regression to compute adjusted odds of CSDS and MDD for 2005-2008, 2009-2012, and 2015-2016. We analyzed the prevalence of A1C ≥ 9.0% [75 mmol/mol], systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, non-HDL cholesterol ≥ 130 mg/dL, and current smoking among adults with diagnosed diabetes by depressive status.The prevalence of CSDS increased among individuals with normal glycemic status from 15.0% (13.5-16.2) to 17.3% (16.0-18.7) (p = 0.03) over 2005-2016. The prevalence of CSDS and MDD remained stable among adults with prediabetes (~ 16% and 1%, respectively) and diabetes (~ 26% and ~3%). After controlling for glycemic, sociodemographic, economic, and self-rated health variables, we found 2-fold greater odds of CSDS among unemployed individuals and 3-fold greater odds among those with fair/poor self-rated health across all survey periods. Cardiometabolic care targets for adults with diagnosed diabetes were stable from 2005 to 2016 and similar across depressive status.One-fourth of adults with diabetes have comorbid CSDS; this prevalence remained stable over 2005-2016 with no change in diabetes care. At the population level, depression does not appear to impact diabetes care, but further research could explore subgroups that may be more vulnerable and could benefit from integrated care that addresses both conditions.

International trends in traditional diabetes complications (cardiovascular, renal, peripheral vascular, ophthalmic, hepatic or neurological diseases) and mortality rates are poorly characterised. An earlier review of studies published up to 2015 demonstrated that most data come from a dozen high-income countries (HICs) in North America, Europe or the Asia–Pacific region and that, in these countries at least, rates of acute glycaemic fluctuations needing medical attention and amputations, myocardial infarction and mortality were all declining over the period. Here, we provide an updated review of published literature on trends in type 2 diabetes complications and mortality in adults since 2015. We also discuss issues related to data collection, analysis and reporting that have influenced global trends in type 2 diabetes and its complications. We found that most data on trends in type 2 diabetes, its complications and mortality come from a small number of HICs with comprehensive surveillance systems, though at least some low- and middle-income countries (LMICs) from Africa and Latin America are represented in this review. The published data suggest that HICs have experienced declines in cardiovascular complication rates and all-cause mortality in people with diabetes. In parallel, cardiovascular complications and mortality rates in people with diabetes have increased over time in LMICs. However, caution is warranted in interpreting trends from LMICs due to extremely sparse data or data that are not comparable across countries. We noted that approaches to case ascertainment and definitions of complications and mortality (numerators) and type 2 diabetes (the denominator) vary widely and influence the interpretation of international data. We offer four key recommendations to more rigorously document trends in rates of type 2 diabetes complications and mortality, over time and worldwide: (1) increasing investments in data collection systems; (2) standardising case definitions and approaches to ascertainment; (3) strengthening analytical capacity; and (4) developing and implementing structured guidelines for reporting of data. Graphical abstract

OBJECTIVE To assess the cost-effectiveness of collaborative versus usual care in adults with poorly controlled type 2 diabetes and depression in India. RESEARCH DESIGN AND METHODS We performed a within-trial cost-effectiveness analysis of a 24-month parallel, open-label, pragmatic randomized clinical trial at four urban clinics in India from multipayer and societal perspectives. The trial randomly assigned 404 patients with poorly controlled type 2 diabetes (HbA1c ≥8.0%, systolic blood pressure ≥140 mmHg, or LDL cholesterol ≥130 mg/dL) and depressive symptoms (9-item Patient Health Questionnaire score ≥10) to collaborative care (support from nonphysician care coordinators, electronic registers, and specialist-supported case review) for 12 months, followed by 12 months of usual care or 24 months of usual care. We calculated incremental cost-effectiveness ratios (ICERs) in Indian rupees (INR) and international dollars (Int’l-$) and the probability of cost-effectiveness using quality-adjusted life-years (QALYs) and depression-free days (DFDs). RESULTS From a multipayer perspective, collaborative care costed an additional INR309,558 (Int’l-$15,344) per QALY and an additional INR290.2 (Int’l-$14.4) per DFD gained compared with usual care. The probability of cost-effectiveness was 56.4% using a willingness to pay of INR336,000 (Int’l-$16,654) per QALY (approximately three times per-capita gross domestic product). The willingness to pay per DFD to achieve a probability of cost-effectiveness >95% was INR401.6 (Int’l-$19.9). From a societal perspective, cost-effectiveness was marginally lower. In sensitivity analyses, integrating collaborative care in clinical workflows reduced incremental costs by ∼47% (ICER 162,689 per QALY, cost-effectiveness probability 89.4%), but cost-effectiveness decreased when adjusting for baseline values. CONCLUSIONS Collaborative care for patients with type 2 diabetes and depression in urban India can be cost-effective, especially when integrated in clinical workflows. Long-term cost-effectiveness might be more favorable. Scalability across lower- and middle-income country settings depends on heterogeneous contextual factors.

Background Race/ethnic disparities in preventable diabetes-specific hospital care may exist among adults with diabetes who have Medicaid coverage. Objective To examine race/ethnic disparities in utilization of preventable hospital care by adult Medicaid enrollees with diabetes across nine states over time. Design Using serial cross-sectional state discharge records for emergency department (ED) visits and inpatient (IP) hospitalizations from the Healthcare Cost and Utilization Project, we quantified race/ethnicity-specific, state-year preventable diabetes-specific hospital utilization. Participants Non-Hispanic Black, non-Hispanic White, and Hispanic adult Medicaid enrollees aged 18–64 with a diabetes diagnosis (excluding gestational or secondary diabetes) who were discharged from hospital care in Arizona, Iowa, Kentucky, Florida, Maryland, New Jersey, New York, North Carolina, and Utah for the years 2008, 2011, 2014, and 2017. Main Measures Non-Hispanic Black-over-White and Hispanic-over-White rate ratios constructed using age- standardized state-year, race/ethnicity-specific ED, and IP diabetes-specific utilization rates. Key Results The ratio of Black-over-White ED utilization rates for preventable diabetes-specific hospital care increased across the 9 states in our sample from 1.4 (CI 95, 1.31–1.50) in 2008 to 1.73 (CI 95, 1.68–1.78) in 2017. The cross-year-state average non-Hispanic Black-over-White IP rate ratio was 1.46 (CI 95, 1.42–1.50), reflecting increases in some states and decreases in others. The across-state-year average Hispanic-over-White rate ratio for ED utilization was 0.67 (CI 95, 0.63–0.71). The across-state-year average Hispanic-over-White IP hospitalization rate ratio was 0.72 (CI 95, 0.69–0.75). Conclusions Hospital utilization by non-Hispanic Black Medicaid enrollees with diabetes was consistently greater and often increased relative to utilization by White enrollees within state programs between 2008 and 2017. Hispanic enrollee hospital utilization was either lower or indistinguishable relative to White enrollee hospital utilization in most states, but Hispanic utilization increased faster than White utilization in some states. Among broader patterns, there is heterogeneity in the magnitude of race/ethnic disparities in hospital utilization trends across states.

Aims/hypothesis We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI. Methods A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010–2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by the Government of India (2014); and prevalence of diabetes from the Indian Council for Medical Research INdia DIABetes study (2008–2015). Results Lifetime risk (95% CI) of diabetes in 20-year-old men and women was 55.5 (51.6, 59.7)% and 64.6 (60.0, 69.5)%, respectively. Women generally had a higher lifetime risk across the lifespan. Remaining lifetime risk (95% CI) declined with age to 37.7 (30.1, 46.7)% at age 60 years among women and 27.5 (23.1, 32.4)% in men. Lifetime risk (95% CI) was highest among obese Indians: 86.0 (76.6, 91.5)% among 20-year-old women and 86.9 (75.4, 93.8)% among men. We identified considerably higher diabetes-free life expectancy at lower levels of BMI. Conclusions/interpretation Lifetime risk of diabetes in metropolitan cities in India is alarming across the spectrum of weight and rises dramatically with higher BMI. Prevention of diabetes among metropolitan Indians of all ages is an urgent national priority, particularly given the rapid increase in urban obesogenic environments across the country.

Purpose Roux-en-Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long-term weight loss in individuals with severe obesity. This is largely attributed to marked reductions in food intake mediated in part by changes in gut-brain communication. Here, we investigated for the first time whether weight loss after RYGB is associated with alterations in central noradrenaline (NA) neurotransmission. Materials and Methods We longitudinally studied 10 individuals with severe obesity (8 females; age 43.9 ± 13.1 years; body mass index (BMI) 46.5 ± 4.8 kg/m2) using (S,S)-[11C]O-methylreboxetine and positron emission tomography to estimate NA transporter (NAT) availability before and 6 months after surgery. NAT distribution volume ratios (DVR) were calculated by volume-of-interest analysis and the two-parameter multilinear reference tissue model (reference region: occipital cortex). Results The participants responded to RYGB surgery with a reduction in BMI of 12.0 ± 3.5 kg/m2 (p p = 0.019) and a general tendency towards reduced DVR throughout the brain. Furthermore, we found a strong positive correlation between pre-surgery DVR in hypothalamus and the change in BMI (r = 0.78; p = 0.01). Conclusion Reductions in BMI after RYGB surgery are associated with NAT availability in brain regions responsible for decision-making and homeostasis. However, these results need further validation in larger cohorts, to assess whether brain NAT availability could prognosticate the outcome of RYGB on BMI. Graphical abstract

Background: data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: in this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (0·05 for all analyses). Interpretation: in this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence. Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review. Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.

Objectives: To evaluate the available evidence of natural honey and its effect on improving lipid profiles among the adult population. Methods: The following databases were searched in May 2020 for randomized controlled trials (RCTs) and crossover studies without any restrictions in language, publication year, or status: CENTRAL, Embase Elsevier, ClinicalTrials.gov, MEDLINE, the WHO International Clinical Trials Registry Platform, and Google Scholar. We included all RCTs and crossover studies that studied the effect of natural honey on improving lipid levels in individuals at any age, for any dose and duration. Trials investigated the intake of honey alone or honey dissolved in water. The comparison groups were no intervention or placebo. Two independent reviewers screened and evaluated the included trials. The third reviewer was involved in resolving any disagreement. Our aim was to evaluate the evidence available regarding the effect of natural honey in improving lipid profile. Results: Seven trials with 370 participants fitted the inclusion criteria. Pooled analysis showed, honey was found to reduce total cholesterol levels with statistical significance (mean difference [MD]: -14.97 mg/dl, 95% CI: 19.61 to -10.32). Honey was associated with a statistically significant increase in high-density lipoprotein (HDL) levels (MD: 1.78 mg/dl, 95% CI: 0.68 to 2.88). There was a statistically significant LDL reduction level (MD: 18.99 mg/dl, 95% CI: -22.79 to -15.20). Finally, honey was found to lower triglyceride levels significantly (MD: 9.68 mg/dl, 95% CI: -15.56 to -3.80). Conclusions: Total cholesterol was significantly reduced with the use of natural honey intake, as well as low-density lipoprotein (LDL), and triglycerides. High-density lipoprotein showed significant increment. Small quantity of honey can be recommended for patients with dyslipidemia. The impact on clinical outcomes such as cardiovascular mortality and morbidity needs to be evaluated in large studies. PROSPERO REG. NO. CRD: 42020130741

BACKGROUND: Collaborative care (CC) is a multicomponent team-based approach to providing mental health care with systematic integration into outpatient medical settings. The 12-month INDEPENDENT CC intervention improved joint disease control measures in patients with both depression and diabetes at 12 and 24 months following randomization. OBJECTIVE: This study investigated the durability of intervention effects on patient outcomes at 36 months following randomization. PARTICIPANTS: Adult patients with poorly controlled T2D and depression in India randomized to CC or usual care. DESIGN: Post hoc analyses of between-group differences in patient outcomes at 36 months post-randomization (N = 331) and maintenance of outcomes from 12 to 36 months (N = 314). MAIN MEASURES: We evaluated combined risk factor improvement since baseline, defined as ≥ 50.0% reduction in Symptom Checklist Depression Scale (SCL-20) scores along with reduction of at least 0.5 percentage point hemoglobin A1C, 5 mmHg systolic blood pressure, or 10 mg/dL low-density lipoprotein cholesterol. Improvements in single risk factors were also examined. KEY RESULTS: There were no between-group differences in improvements since baseline in multiple or single risk factors at 36 months. Patients in the CC group with improved outcomes at 12 months were more likely to maintain a ≥ 50.0% reduction since baseline in SCL-20 scores (CC [54.9%] vs. UC [40.9%]; RR: 1.27 [95% CI: 1.04, 1.56]) and 0.5 percentage point reduction since baseline in hemoglobin A1C (CC [31.9%] vs. UC [19.5%]; RR: 1.64 [95% CI: 1.11, 2.41]) at 36 months. CONCLUSIONS: While improvements since baseline in patient outcomes did not differ between the collaborative care and usual care groups at 36 months, patients who received CC were more likely to maintain improvements in depressive symptoms and glucose levels at 36 months if they had achieved these improvements at the end of active intervention. TRIAL REGISTRATION NUMBER: NCT02022111.

Background: People of South Asian ancestry are at high risk for type 2 diabetes, but the time to disease progression in this population is not fully understood. Methods: We analyzed data from 2714 adults aged ≥20 years, enrolled in the Chennai site of the prospective Cardiometabolic risk reduction in South Asia (CARRS) study. Participants had 75g OGTT and HbA1c measurements. We defined normal glucose tolerance (NGT) , isolated impaired fasting glucose (iIFG) , impaired glucose tolerance (IGT) , and diabetes based on ADA criteria. We constructed continuous chain Markov models to estimate the transition through multiple states (NGT -> iIFG -> diabetes; NGT -> IGT -> diabetes) . The annual and five-year transition probability among states was estimated based on transition intensity. Results: Participants were, on average, 38.4 (range 20-89) years old, and 40.1% were male. Prevalence of iIFG and IGT was 16.9% and 7.3%, respectively. Over 5 years of follow up, the progression rates were: NGT to iIFG, 36.3 (95% CI: 32.5, 40.5) per 1,000 person-years (PYR) , NGT to IGT, 27.4 (95% CI: 24.1, 31.1) per 1,000 PYR, iIFG to diabetes 47.3 (95% CI: 40.4, 55.4) per 1,000 PYR, and IGT to diabetes 77.1 (95% CI: 65.1, 91.3) per 1,000 PYR. The estimated annual probability of remaining as NGT, iIFG, and IGT were 95.2% (94.7%, 95.8%) , 87.3% (85.5%, 89.0%) ;%) , and 81.9% (79.6%, 84.3%) %) , respectively. Assuming unidirectional transition, the annual probability of conversion from NGT to iIFG, and iIFG to diabetes were 4.5% (3.9%, 4.9%) , and 12.7% (10.9%, 14.5%) , respectively; and NGT to IGT, and IGT to diabetes were 3.8% (3.3%, 4.2%) and 18.1% (15.7%, 20.3%) . The estimated mean sojourn time (years) in each state were: NGT 20.5 (18.2, 23.2) , iIFG 7.4 (6.4, 8.6) , and IGT 5.0 (4.4, 5.8) , respectively. Conclusion: The course to diabetes in South Asians is rapid once prediabetes sets in, allowing a window of only 5-7.4 years to implement proven prevention. Innovative prevention efforts in normoglycemic people may be needed to prevent prediabetes in the first place. Disclosure K.Narayan: n/a. H.H.Chang: None. N.Tandon: None. V.Mohan: None. D.Kondal: None. L.R.Staimez: None. R.Anjana: None. U.Gujral: None. M.Deepa: None. S.A.Patel: Research Support; Johnson & Johnson. M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. D.Prabhakaran: None. Funding The National Heart, Lung, and Blood Institute (NHLBI) , National Institutes of Health (HHSN268200900026C)

Background: Diabetes is a key risk factor for severe COVID-19 (i.e., hospitalization, mortality) . Whether diabetes is also a risk factor for post-acute sequelae of COVID-19 (PASC) , also known as long COVID, is unknown. Methods: We conducted a scoping literature review on January 27, 2022 using the keyword terms ‘long hauler’, ‘long COVID-19’, ‘post-acute sequalae’, and ‘persistent COVID-19’ combined with the operator OR, with AND ‘diabetes’, AND ‘COVID-19 [MeSH Term]’. We included all peer-reviewed full-text observational research studies published in English between January 1, 2020 and January 27, 2022 that reported on the risk of PASC in people with and without diabetes with a minimum of 4-weeks follow-up after COVID-19 diagnosis, and narratively synthesized results. Results: Among 39 studies identified, seven were included in the review and are summarized in Table 1. Overall, we found that 43% of studies identified diabetes as a potent risk factor for PASC (all odds ratios were >4) . However, this conclusion is limited by the heterogeneity of studies with regard to PASC definitions (e.g., ongoing symptoms of fatigue, cough, dyspnea etc.) , populations at risk (hospitalized vs. non-hospitalized populations) , and follow-up times (range 4 weeks to 7 months) . Conclusions: More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for PASC. In the meantime, careful monitoring of people with diabetes for development of PASC may be advised. Disclosure J. L. Harding: None. M. K. Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. J. C. Gander: None. R. E. Patzer: None.

Background: Among South Asians, women have higher prevalence of diabetes than men, but few studies have examined gender differences in incidence. Methods: We analyzed data from 2714 adults aged ≥20 years, enrolled in the Chennai site of prospective Cardiometabolic risk reduction in South Asia (CARRS) study. We defined normal glucose tolerance (NGT) , isolated impaired fasting glucose (iIFG) , impaired glucose tolerance (IGT) , and diabetes based on ADA criteria. We estimated incidence densities for: NGT (n=2205) to iIFG and iIFG (n=641) to diabetes; NGT (n=2205) to IGT; and IGT (n=341) to diabetes. Results: Prevalence of iIFG was higher in women (20.5% vs. 11.8%) , while prevalence of IGT was lower (6.6% vs. 8.5%) than in men. During median 2.6 y (IQR: 0.7, 5.8) of follow-up, 316 individuals progressed from NGT to iIFG, 239 from NGT to IGT, 155 from iIFG to diabetes, and 135 from IGT to diabetes. Overall, incidence (95% CI) of NGT to iIFG was higher than incidence of NGT to IGT (36.3 [32.5, 40.5] vs. 27.4 [24.1, 31.1] per 1,000 person-years [PYR], respectively) . However, the incidence of iIFG to diabetes was lower than incidence of IGT to diabetes (47.3 [40.4, 55.4] vs. 77.1 [65.1, 91.3] per 1,000 PYR, respectively) . Compared with men, women had higher conversion from NGT to iIFG (42.1 [36.9, 48] vs. 27.7 [22.7, 33.8]) , but lower incidence of NGT to IGT, 22.9 (19.2, 27.4) vs. 34.2 (28.5, 40.9) . Women had higher conversation both from iIFG to diabetes [49.0 (40.8,58.8) vs. 43.1 (31.6,58.7) ] and IGT to diabetes (87.7 [70.5,109.0] vs. 65.3 [50.0,85.2]) . In Cox models adjusting for age, BMI and family history of diabetes, women were 1.41 times (95% CI: 1.07,1.84) likely to convert from NGT to iIFG compared to men, but, men are 1.76 (1.33, 2.34) times at risk from NGT to IGT. There was no gender difference for conversion from iIFG or IGT to diabetes. Conclusion: Prevalence and incidence of iIFG is higher in South Asian women than men, while prevalence and incidence of IGT is higher in men. Conversion from iIFG or IGT to diabetes is similar among genders. Disclosure K.Narayan: n/a. H.H.Chang: None. N.Tandon: None. V.Mohan: None. D.Kondal: None. L.R.Staimez: None. R.Anjana: None. U.Gujral: None. M.Deepa: None. S.A.Patel: Research Support; Johnson & Johnson. M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. D.Prabhakaran: None. Funding The National Heart, Lung, and Blood Institute (NHLBI) , National Institutes of Health (HHSN268200900026C)

In 2021, the US Preventive Services Task Force (USPSTF) expanded the recommended age range for prediabetes and diabetes screening among those with overweight/obesity to 35-70 years. Using 2017 to pre-pandemic March 2020 National Health and Nutrition Examination Survey data, we applied these screening criteria to assess their performance in a nationally representative sample. We included 3243 non-pregnant adults aged ≥18 years without diagnosed diabetes. Screening eligibility was determined based on participants' age and measured body mass index (BMI) [≥23kg/m2 for non-Hispanic (NH) Asian adults and ≥25kg/m2 for other ethnic groups]. Dysglycemia was defined based on A1c ≥5.7% or fasting plasma glucose ≥100mg/dL. We compared participant characteristics by USPSTF eligibility. We also assessed performance [sensitivity, specificity, positive predictive value (PPV) , and negative predictive value (NPV) ] of the screening criteria for detecting dysglycemia overall and by ethnicity. During 2017-2020, 44.4% of US adults aged 35-70 years were eligible for screening, representing 95.9 million US adults. Relative to adults who were ineligible, those who were eligible had a higher burden of diabetes risk factors, as well as greater proportions of some racial ethnic groups, higher proportion of those with less than a high school education, and more likely to be living in poverty. The performance characteristics of the USPSTF screening criteria were: sensitivity 59.4% (95% CI: 56.4-62.4) ; specificity 68.6% (65.1-71.9) ; PPV 62.4% (59.2-65.6) ; and NPV 65.8% (61.9-69.5) . The sensitivity by ethnicity was as follows: NH White adults 59.1% (55.4-62.7) ; NH Black adults 63.6% (57.8-68.9) ; Hispanic adults 62.0% (55.0-68.5) ; and NH Asian adults 57.3% (46.6-67.3) . Screening based on the 2021 USPSTF criteria will detect approximately 60% of US adults with dysglycemia, which was similar across ethnic groups. Disclosure M.J.O'brien: None. K.M.Bullard: None. Y.Zhang: n/a. S.Bailey: Consultant; Lundbeck, Luto, Pfizer Inc., Sanofi, Research Support; Eli Lilly and Company, Gordon and Betty Moore Foundation, Lundbeck, Merck & Co., Inc., Pfizer Inc., Retirement Research Foundation for Aging. S.Khan: None. R.T.Ackermann: Consultant; UnitedHealth Group. M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. S.R.Benoit: None. G.Imperatore: None. C.S.Holliday: None.

To identify prediabetes/diabetes, the US Preventive Services Task Force (USPSTF) has recommended glucose testing in 40-70 year olds (2015) and now 35-70 year olds (2021) with overweight/obesity. Since 2002, the American Diabetes Association (ADA) has recommended prediabetes/diabetes screening based on a larger set of diabetes risk factors. We analyzed cross-sectional National Health and Nutrition Examination Survey data from 6,0non-pregnant US adults aged ≥18 years without diagnosed diabetes. For USPSTF 2015 and 2021, and ADA guidelines, we described which adults were eligible and ineligible for glucose testing, and proportions reporting receiving testing. We assessed sensitivity and specificity in identifying prediabetes (fasting plasma glucose [FPG] 100-125mg/dL or A1c 5.7-6.4% or both) or undiagnosed diabetes (FPG≥126mg/dL or A1c≥6.5% or both) . During 2013-2018, an estimated 76.7 million, 90.4 million, and 157.7 million US adults met eligibility for glucose testing by the USPSTF 2015, 2021, and ADA guidelines, respectively. Eligibility and proportions receiving testing varied by guideline (Figure 1) . Across definitions of prediabetes/diabetes, ADA recommendations were most sensitive (range: 91.0-99.1%) and least specific (24.1-35.3%) ; 2015 (sensitivity: 51.9-59.4%; specificity: 63.2-74.5%) and 2021 USPSTF (sensitivity: 57.5-66.6%; specificity: 56.6-67.1%) guideline sensitivity and specificity were comparable. Disclosure M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. G.Imperatore: None. S.R.Benoit: None. C.S.Holliday: None. M.J.O'brien: None. J.B.Echouffo tcheugui: None. K.M.Bullard: None. Funding MKA was partially supported by the Georgia Center for Diabetes Translation Research funded by the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)

The medical costs of treating type 2 diabetes (T2D) can be considered a counterfactual to measure the value for preventing T2D. This study examined changes in the cost-effectiveness of the structured lifestyle intervention (SLI) to prevent T2D, attributable to the sharp increase in the costs of T2D between 20 and 2018. We developed a patient-level discrete-time microsimulation model for diabetes progression and mortality in people eligible for SLI as specified in the National Diabetes Prevention Program (NDPP) using data from the 2009-20 National Health and Nutrition Examination Survey (NHANES) with linked National Death Index, and published literature. We used the Medical Expenditure Panel Survey to develop a health utility equation (2018 data) and two cost equations (20 and 2018 data) . We simulated the long-term health and economic consequences of SLI using the simulation model based on 20 and 2018 cost equations, respectively. We took a payers’ perspective, and all costs were standardized to 2018 USD. The incremental net benefit (INB) was estimated using a $50,000/QALY. The SLI achieved cost-saving over a 20-year time horizon in a scenario using 2010’s costs but only 9 years under 2018’s costs. Based on 20 costs, SLI costs below $997 and $2,153 would make the SLI cost-saving and cost-effective, respectively, over a 20-year window. Based on 2018 costs, if SLI costs were below $1,479 and $2,635, respectively, it would be cost-saving and cost-effective over 20 years. Subgroup analysis suggested the SLI was more cost-effective in the Hispanic adults (INB:$5,383) than non-Hispanic white (INB: $2,192) and black (INB:$2,364) adults. From 20 to 2018, the increasing medical costs for treating T2D has led to a higher likelihood and shorter time horizon for SLI to be cost-saving. This suggests that payers can raise reimbursements for SLI programs to make the adoption of these programs more feasible for delivery systems while maintaining economic value. Disclosure W.Huang: None. D.Guan: None. S.Niu: None. M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. Y.Zhang: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

To determine whether obesity-associated metabolites are associated with type 2 diabetes (T2DM) risk among South Asians.Serum-based nuclear magnetic resonance imaging metabolomics data were generated from two South Asian population-based prospective cohorts from Karachi, Pakistan: CARRS1 (N = 4017) and CARRS2 (N = 4802). Participants in both cohorts were followed up for 5 years and incident T2DM was ascertained. A nested case-control study approach was developed to select participants from CARRS1 (NIn a combined sample of the CARRS1 and CARRS2 cohorts, out of 224 metabolites, 12 were associated with general obesity and, of these, one was associated with incident T2DM. Fifteen out of 224 metabolites were associated with central obesity and, of these, 10 were associated with incident T2DM. The higher level of total cholesterol in high-density lipoprotein (HDL) was associated with reduced T2DM risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.53, 0.86; P = 1.2 × 10Total cholesterol in HDL and cholesterol esters in large VLDL particles may be an important biomarker in the identification of early development of obesity-associated T2DM risk among South Asian adults.

OBJECTIVE To analyze national and state-specific trends in diabetes-related hospital admissions and determine whether disparities in rates of admission exist between demographic groups and geographically dispersed states. RESEARCH DESIGN AND METHODS We conducted serial cross-sectional analyses of the National Inpatient Sample (2008, 2011, 2014, and 2016) and State Inpatient Databases for Arizona, Florida, Kentucky, Iowa, Maryland, Nebraska, New Jersey, New York, North Carolina, Utah, and Vermont for 2008, 2011, 2014, and 2016/2017 among adult patients with type 1 and type 2 diabetes–related ICD codes (ICD-9 [250.XX] or ICD-10 [E10.XXX, E11.XXX, and E13.XXX]. We measured hospitalization rates for people with diabetes (all-cause hospitalizations) and for admissions with a primary diagnosis of diabetes or diabetes-related complications (diabetes-specific hospitalizations) per 10,000 people per year. RESULTS Nationally, all-cause and diabetes-specific hospitalizations declined by 3.1% (95% CI −5.5, −0.7) and 19.1% (95% CI −21.6, −16.6), respectively, over 2008 to 2016. The analysis of individual states showed that diabetes-specific admissions in individuals ≥65 years old declined during this time (16.3–48.8% decrease) but increased among patients 18–29 years old (10.5–81.5% increase) and that rural diabetes-specific admissions decreased in just over half of the included states (15.2–69.2% decrease). There were no differences in changes in admission rates among different racial/ethnic groups. CONCLUSIONS Overall, rates of diabetes-related hospitalizations decreased over 2008 to 2016/2017, but there were large state-level differences across subgroups of patients. The rise in diabetes hospitalizations among young adults is a cause for concern. These state- and subpopulation-level differences highlight the need for state-level policies and interventions to address disparities in diabetes health care use.

Summary Background Improving hypertension control is an important global health priority, yet, to our knowledge, there is no direct evidence on the relationship between blood pressure and mortality in sub-Saharan Africa. We aimed to investigate the relationship between systolic blood pressure and mortality in South Africa and to assess the comparative effectiveness of different systolic blood pressure targets for clinical care and population-wide hypertension management efforts. Methods In this country-wide, population-based cohort study, we used longitudinal data on adults aged 30 years and older from five waves (2008, 2010–11, 2012, 2014–15, and 2017) of the South African National Income Dynamics Study. We estimated the relationship between systolic blood pressure and 6-year all-cause mortality and compared the mortality reductions associated with lowering systolic blood pressure to different targets (120 mm Hg, 130 mm Hg, 140 mm Hg, 150 mm Hg). We also estimated the mean blood pressure reduction required to achieve each target, the share of the population in need of management, and the number needed to treat (NNT) to avert one death under different hypothetical population-wide scale-up scenarios. Findings Of the 8338 age-eligible respondents in the 2010–11 survey, 4993 had all required data and were included in our study. We found a weak, non-linear relationship between systolic blood pressure and 6-year mortality, with larger incremental mortality benefits at higher systolic blood pressure values: reducing systolic blood pressure from 160 mm Hg to 150 mm Hg was associated with a relative risk of mortality of 0·95 (95% CI 0·90 to 0·99; p=0·033), reducing systolic blood pressure from 150 mm Hg to 140 mm Hg had a relative risk of 0·96 (0·91 to 1·01; p=0·12), with no evidence of incremental benefits of reducing systolic blood pressure below 140 mm Hg. At the population level, reducing systolic blood pressure to 150 mm Hg among all those with a starting systolic blood pressure of more than 150 mm Hg was associated with the lowest NNT (n=50), 3·3 deaths averted (95% CI −0·6 to 0·3) per 1000 population, blood pressure management for 16% (95% CI 15·2 to 17·3) of individuals, and a −2·7 mm Hg mean change in systolic blood pressure required to achieve the 150 mm Hg scale-up target (−3·0 to −2·5; p Interpretation The relationship between systolic blood pressure and mortality is weaker in South Africa than in high-income and many low-income and middle-income countries. As such, we do not find compelling evidence in support of targets below 140 mm Hg and find that scaling up management based on a 150 mm Hg target is more efficient in terms of the NNT compared with strategies to reduce systolic blood pressure to lower values. Funding None

Surgery is regarded by many as the go-to treatment option for severe obesity; yet how physically altering the gastrointestinal tract produces such striking results on body weight and overall metabolic health is poorly understood. In a recent issue of Cell Reports Ye et al. (2020) compare mouse models of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the two most commonly performed weight loss surgeries in the clinic today, to show that the former reconfiguring procedure selectively increases resting metabolic rate through splanchnic nerve-mediated browning of mesenteric white fat. More significantly, they demonstrate that this effect for RYGB is required for the maintained negative energy balance and improved glycemic control that it confers.

Ambient air pollution, specifically particulate matter of diameter 3 (interquartile range, 87.6–95.7) and 82.4 μg/m 3 (interquartile range, 68.4–107.0), respectively. We observed higher average systolic BP (1.77 mm Hg [95% CI, 0.97–2.56] and 3.33 mm Hg [95% CI, 1.12–5.52]) per interquartile range differences in monthly and annual exposures, respectively, after adjusting for covariates. Additionally, interquartile range differences in long-term exposures of 1, 1.5, and 2 years increased the risk of incident hypertension by 1.53× (95% CI, 1.19–1.96), 1.59× (95% CI, 1.31–1.92), and 1.16× (95% CI, 0.95–1.43), respectively. Observed effects were larger in individuals with higher waist-hip ratios. Our data strongly support a temporal association between high levels of ambient air pollution, higher systolic BP, and incident hypertension. Given that high BP is an important risk factor of cardiovascular disease, reducing ambient air pollution is likely to have meaningful clinical and public health benefits.

OBJECTIVE Diabetes prevalence is increasing rapidly in rural areas of low- and middle-income countries (LMICs), but there are limited data on the performance of health systems in delivering equitable and effective care to rural populations. We therefore assessed rural-urban differences in diabetes care and control in LMICs. RESEARCH DESIGN AND METHODS We pooled individual-level data from nationally representative health surveys in 42 countries. We used Poisson regression models to estimate age-adjusted differences in the proportion of individuals with diabetes in rural versus urban areas achieving performance measures for the diagnosis, treatment, and control of diabetes and associated cardiovascular risk factors. We examined differences across the pooled sample, by sex, and by country. RESULTS The pooled sample from 42 countries included 840,110 individuals (35,404 with diabetes). Compared with urban populations with diabetes, rural populations had ∼15–30% lower relative risk of achieving performance measures for diabetes diagnosis and treatment. Rural populations with diagnosed diabetes had a 14% (95% CI 5–22%) lower relative risk of glycemic control, 6% (95% CI −5 to 16%) lower relative risk of blood pressure control, and 23% (95% CI 2–39%) lower relative risk of cholesterol control. Rural women with diabetes had lower achievement of performance measures relating to control than urban women, whereas among men, differences were small. CONCLUSIONS Rural populations with diabetes experience substantial inequities in the achievement of diabetes performance measures in LMICs. Programs and policies aiming to strengthen global diabetes care must consider the unique challenges experienced by rural populations.

Background Susceptibility to metabolic diseases may be influenced by mitochondrial genetic variability among people living with human immunodeficiency virus (HIV; PLWH), but remains unexplored in populations with African ancestry. We investigated the association between mitochondrial DNA (mtDNA) haplogroups and the homeostatic model assessments of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), as well as incident diabetes mellitus (DM), among Black women living with or at risk for HIV. Methods Women without DM who had fasting glucose (FG) and insulin (FI) data for ≥2 visits were included. Haplogroups were inferred from genotyping data using HaploGrep. HOMA-B and HOMA-IR were calculated using FG and FI data. Incident DM was defined by a combination of FG ≥ 126 mg/dL, the use of DM medication, a DM diagnosis, or hemoglobin A1c ≥ 6.5%. We compared HOMA-B, HOMA-IR, and incident DM by haplogroups and assessed the associations between HOMA-B and HOMA-IR and DM by haplogroup. Results Of 1288 women (933 living with HIV and 355 living without HIV), PLWH had higher initial HOMA-B and HOMA-IR than people living without HIV. PLWH with haplogroup L2 had a slower decline in HOMA-B per year (Pinteraction = .02) and a lower risk of incident DM (hazard ratio [HR], 0.51; 95% confidence interval [CI], .32–.82) than PLWH with other haplogroups after adjustments for age, body mass index, combination antiretroviral therapy use, CD4 cell counts, and HIV RNA. The impact of HOMA-IR on incident DM was less significant in those with haplogroup L2, compared to non-L2 (HR, 1.28 [95% CI, .70–2.38] vs 4.13 [95% CI, 3.28–5.22], respectively; Pinteraction < .01), among PLWH. Conclusions Mitochondrial genetic variation is associated with β-cell functions and incident DM in non-Hispanic, Black women with HIV and alters the relationship between insulin resistance and DM.

Considerable evidence supports transradial angiography and intervention in patients with acute coronary syndrome, with an emphasis on decreasing major bleeding and access site vascular complications. Patients undergoing invasive treatment are at greatest risk of bleeding and have the most to gain. The radial advantage has consistently been shown to translate into reduced mortality in pooled data analyses. The benefits of transradial access have been demonstrated across the acute coronary syndrome spectrum and in both sexes. A radial-first strategy should be the default approach and continuous efforts should be made to increase operator expertise of transradial access in these patients.

Background/Aim: The worldwide prevalence of obesity has increased dramatically over the past years. In the Arab region, 66%–75% of adults and 25%–40% of children are either overweight or obese. Bariatric surgery has become the most effective approach for managing obesity and its co-morbidities. An expected outcome of bariatric surgery is cholelithiasis, which is one of the established risk factors of rapid weight loss. The aim of this study is to detect the incidence of symptomatic cholelithiasis among bariatric patients. Patients and Methods: A retrospective cohort study on 711 patients aged between 18 and 60 who underwent laparoscopic sleeve gastrectomy (LSG) was conducted at King Saud University Medical City from January 2016 to January 2018. Results: The postoperative incidence of symptomatic cholelithiasis was 3.5%. The mean duration of symptom development was 12.4 months. The rates of weight loss at 6 and 12 months for patients with symptomatic cholelithiasis were 28.94 ± 4.89% and 38.51 ± 6.84%, respectively (P = 0.002), which were significantly higher than in patients without symptomatic cholelithiasis during the same follow-up period (24.41 ± 6.6% and 32.29 ± 10.28%), respectively; (P = 0.012). Conclusion: We found a 3.5% incidence of symptomatic cholelithiasis among post-LSG patients in a period of 2 years. Rapid weight loss was the only risk factor that contributed to the development of post-LSG gallbladder disease. Statistical Analysis Used: Results were expressed as absolute numbers and percentages for categorical variables and as mean and standard deviation for continuous variables. A paired sample t-test was performed to determine significant differences between means at different time stamps. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 23.0.

Fasting during Ramadan is one of the five pillars of Islam and is obligatory for all healthy Muslims from the age of puberty. Though individuals with some illness and serious medical conditions, including some people with diabetes, can be exempted from fasting, many will fast anyway. It is of paramount importance that people with diabetes that fast are given the appropriate guidance and receive proper care. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DaR) International Alliance have come together to provide a substantial update to the previous guidelines. This update includes key information on fasting during Ramadan with type 1 diabetes, the management of diabetes in people of elderly ages and pregnant women, the effects of Ramadan on one's mental wellbeing, changes to the risk of macrovascular and microvascular complications, and areas of future research. The IDF-DAR Diabetes and Ramadan Practical Guidelines 2021 seek to improve upon the awareness, knowledge and management of diabetes during Ramadan, and to provide real-world recommendations to health professionals and the people with diabetes who choose to fast.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

OBJECTIVE We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS This was a nationwide, retrospective study of adults (≥18 years old) with diabetes/ESKD, from the United States Renal Data System registry, between 2013 and 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years. Event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region. RESULTS Among 521,789 adults with diabetes/ESKD (median age 65 years [interquartile range 57–73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1,000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, respectively, the risks decreased with age and were lowest in older patients (≥75 vs. 18–44 years old: incidence rate ratio 0.35, 95% CI 0.33–0.37, and 0.03, 0.02–0.03), women (1.09, 1.06–1.12, and 1.44, 1.35–1.54), and those with smoking (1.36, 1.28–1.43, and 1.71, 1.53–1.91), substance abuse (1.27, 1.15–1.42, and 1.53, 1.23–1.9), retinopathy (1.10, 1.06–1.15, and 1.36, 1.26–1.47), and insulin therapy (vs. no therapy; 0.60, 0.59–0.63, and 0.44, 0.39–0.48). For hypoglycemia, specifically, additional risk was conferred by Black race (1.11, 1.08–1.15) and amputation history (1.20, 1.13–1.27). CONCLUSIONS In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in nondialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected.

Ventricular fibrillation (VF) is a lethal cardiac arrhythmia that leads to cardiac arrest and death. It is especially deadly when it fails to respond to conventional treatment with electrical defibrillation. This arrhythmia is often triggered by acute myocardial ischemia, but in rare cases, it can be precipitated by direct myocardial trauma. Most patients with traumatic cardiac arrest do not survive, but in a minority of patients, an emergency thoracotomy may improve survival by addressing reversible causes such as haemorrhage control, relief of cardiac tamponade, and direct wound closure. We present an unusual case of a traumatic cardiac arrest, presenting with refractory ventricular fibrillation due to a cardiac laceration in a young trauma patient with an isolated chest injury.

Background Pain is one of the common and devastating symptoms that affects millions of cancer patients globally. Despite published guidelines and education on the assessment and management of cancer-related pain, underestimated or undertreated pain continues to be a considerable worldwide public health concern among cancer patients. In this study, we aimed to assess physicians’ adherence to the World Health Organization (WHO) guidelines in the management and assessment of pain in oncology patients based on the available score of pain in the Princess Noorah Oncology Center (PNOC) at the King Abdulaziz Medical City in Jeddah. Methodology This cross-sectional, retrospective chart review study studied 451 patients (selected through computerized random sampling) who were admitted to the PNOC during the study period. Results The pain was assessed using the Brief Pain Inventory in almost all patients (n = 450, 99.8%). The pain was categorized as mild in 386 (85.6%) patients, moderate in 46 (10.2%) patients, and severe in 19 (4.2%) patients. Opioid prescriptions were significantly higher among patients with moderate (76.1%) and severe pain (89.5%) compared to those with mild pain (39.1%; p < 0.0001). Conclusions The practice of pain documentation for cancer patients was adequate as indicated by reporting the pain scores of 99.8% of inpatients. Patients with moderate and severe pain were more likely to receive opioids and a combination of opioids plus non-opioid analgesics, whereas the prescription of analgesics was predicted by experiencing moderate cancer pain.

Background Buruli ulcer disease (BUD) is a necrotic skin neglected tropical disease (NTD) that has both a mental and physical health impact on affected individuals. Although there is increasing evidence suggesting a strong association between neglected tropical diseases (NTDs) and mental illness, there is a relative lack of information on BUD’s impact on the mental health and quality of life (QoL) of affected individuals in Ghana. This study is to assess the impact of BUD on mental health and quality of life of patients with active and past BUD infection, and their caregivers. Methods We conducted a case control study in 3 BUD endemic districts in Ghana between August and November 2019. Face-to-face structured questionnaire-based interviews were conducted on BUD patients with active and past infection, as well as caregivers of BUD patients using WHO Quality of Life scale, WHO Disability Assessment Schedule, Self-Reporting Questionnaire, Buruli Ulcer Functional Limitation Score and Hospital Anxiety and Depression Scale data tools. Descriptive statistics were used to summarize the characteristics of the study participants. Participant groups were compared using student t test and chi-square (χ2) or Fisher’s exact tests. Mean quality of life scores are reported with their respective 95% confidence intervals. Data was analysed using STATA statistical software. Results Our results show that BUD patients with active and past infection, along with their caregivers, face significant levels of distress and mental health sequelae compared to controls. Depression (P = 0.003) was more common in participants with active (27%) and past BU infection (17%), compared to controls (0%). Anxiety was found in 42% (11/26) and 20% (6/29) of participants with active and past BUD infection compared to 14% (5/36) of controls. Quality of life was also significantly diminished in active BUD infection, compared to controls. In the physical health domain, mean QoL scores were 54 ± 11.1 and 56 ± 11.0 (95% CI: 49.5‒58.5 and 52.2‒59.7) respectively for participants with active infection and controls. Similarly in the psychological domain, scores were lower for active infection than controls [57.1 ± 15.2 (95% CI: 50.9‒63.2) vs 64.7 ± 11.6 (95% CI: 60.8‒68.6)]. Participants with past infection had high QoL scores in both physical [61.3 ± 13.5 (95% CI: 56.1‒66.5)] and psychological health domains [68.4 ± 14.6 (95% CI: 62.7‒74.0)]. Conclusions BUD is associated with significant mental health distress and reduced quality of life in affected persons and their caregivers in Ghana. There is a need for integration of psychosocial interventions in the management of the disease. Graphic abstract

Anti-D immunoglobulin (anti-D) therapy is cheaper and has a shorter infusion time than intravenous immunoglobulin G (IgG), but their comparative effects in the treatment of acute immune thrombocytopenia (ITP) have not been studied thoroughly. The aim of this study was to compare the effect of anti-D and intravenous IgG in the treatment of acute ITP in children.The medical records of children diagnosed with acute ITP between January, 2008, and January, 2018, at Al-Rantisy Specialized Pediatric Hospital (a tertiary care centre) in Gaza were reviewed. Patients who received either intravenous anti-D (75 μg/kg, single dose) or intravenous IgG (2 g/kg, divided doses) as initial treatment for ITP were included in this retrospective study. Data on patient demographics, hospital stay period, and adverse drug reactions were collected for analysis. Laboratory results, including platelet counts and haemoglobin levels, were evaluated before treatment, and after 1, 3, 5, and 7 days of treatment. The therapy response was defined as the time taken to increase the platelet count to at least 20,000 platelets per μL.Data from 134 patients (mean age, 5·8 years; range, 1·1-10·4 years) were included for analysis. 32% of patients (43 of 134) received anti-D and 68% of patients (91) received intravenous IgG. Mean pre-treatment platelet counts were 6420 platelets per μL and 8750 platelets per μL for anti-D and intravenous IgG groups, respectively. The platelet count increased significantly after 1, 3, 5, and 7 days of treatment in both groups (p0·001). After 24 h of treatment, 58% of patients (25 of 43) in the anti-D group and 55% of patients (50 of 91) in the intravenous IgG group had platelet counts of over 20 000 platelets per μL. Moreover, all of the patients in both groups had more than 20 000 platelets per μL after 7 days of therapy. There were no significant differences in platelet count after treatment between the two groups. Haemoglobin levels decreased during the 72 h after treatment (anti-D group, mean 0·8 g/dL, range, 0·1-1·4 g/dL; intravenous IgG group, mean 0·5 g/dL, range, 0·2-1·2 g/dL; p=0·237), but increased on days 5 and 7 in both groups. The changes in haemoglobin after treatment were similar in both study groups. No patient developed severe anaemia requiring medical intervention. The average length of hospital stay was significantly shorter in the anti-D group than in the intravenous IgG group (1·8 days and 3·2 days, respectively; p0·0001). Fewer adverse effects (headache, vomiting, chills) were reported in children who received anti-D therapy.In this analysis, anti-D was as effective as intravenous IgG in the treatment of children with acute ITP. Given that patients in the anti-D group experienced fewer adverse effects and shorter hospitalisation times than patients in the intravenous IgG group, this suggests that anti-D is a good substitute for intravenous IgG in the treatment of children with acute ITP.None.

Background: Recent data from randomised and observational studies have reported non-inferior outcomes for transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) in intermediate-risk patients. We performed a systematic review to evaluate the mortality of TAVI compared to SAVR in intermediate-risk patients. Methods: A comprehensive search of four major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to 29 April 2016. We included original research studies reporting data on TAVI and SAVR in intermediate-risk patients. We compared the outcomes of TAVI to SAVR. Results: A total of 2,375 and 2,377 intermediate-risk patients underwent TAVI and SAVR respectively. The 30-day all-cause (p = 0.07), 30-day cardiac (p = 0.53), and 12-month all-cause mortality (p = 0.34) was similar between the two groups. However, TAVI through transfemoral access had a significantly lower mortality than SAVR (OR 0.58, p = 0.006). The incidence of ≥moderate aortic incompetence (p < 0.00001) and pacemaker implantation (p < 0.0001) was higher in the TAVI group. Conclusions: In the intermediate-risk patients, the 30-day and 12-month mortality are similar between TAVI and SAVR. Increased operator experience and improved device technology have led to a significant reduction in mortality in intermediate-risk patients undergoing TAVI. Refereed/Peer-reviewed

Mohammed A Omair,1 Fatima Al Suwayeh,2 Alanoud Almashaan,2 Eman Alqurtas,1 Mohammed K Bedaiwi,1 Ibrahim Almaghlouth,1 Abdulaziz Alkahalaf,1 Haya M Almalaq2 1Rheumatology Unit, Department of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mohammed A OmairRheumatology Division, Department of Medicine (38), College of Medicine King Saud University, PO Box 2925, Riyadh, 11461, Saudi ArabiaTel/Fax +966-1-467-1546Email momair@ksu.edu.saPurpose: A simple measure to assess drug adherence in Saudi patients with rheumatoid arthritis (RA) is required. The aim of this study was to translate and validate the 5-Item Compliance Questionnaire for Rheumatology (CQR5) into Arabic.Patients and Methods: The questionnaire was translated and culturally adapted to Arab patients in six steps: initial translation, synthesis of the translation, back translation, expert committee review, test of the pre-final version, and development of the Arabic CQR5 (ACQR-5). The resulting version was tested for validity in patients with RA.Results: A total of 103 adult patients with RA were recruited from rheumatology clinics at a university hospital in Riyadh, Saudi Arabia. After extensive translation, the final tool (CQR) was piloted in 15 patients. The final validation was performed with 88 patients. Of these, 80 (90.9%) were female and 43.2% were seropositive. The mean (±SD) age and disease duration were 50 (± 13) and 11.4 (± 8.2) years, respectively. Cronbach’s alpha reliability was 0.886, and the Kaiser-Meyer-Olkin measure of sampling adequacy for factor analysis was 0.870 (p< 0.001). The mean ACQR-5 was 17.78 (2.70), with 14 (15.9%) classified as low adherents and the remaining 74 (84.1%) as high adherents. Binary logistic regression revealed that increasing age (odds ratio [OR] 1.082, 95% confidence interval [CI]: 1.025– 1.142, p=0.005) and a trend toward the presence of other comorbidities (OR 3.111, 95% CI: 0.961– 10.070, p=0.058) were associated with low adherence.Conclusion: ACQR-5 is a simple and feasible tool for identifying adherence levels in patients with RA in Saudi Arabia. A high level of adherence was observed in this study. Additional studies are required to assess ACQR-5 validity and adherence levels in a larger, more diverse population.Keywords: adherence, rheumatoid arthritis, compliance questionnaire for rheumatology, Saudi Arabia