Effects of long-term HbA1c variability on serious infection risks in patients with type 2 diabetes and the influence of age, sex and ethnicity: A cohort study of primary care data.

AIMS: Long-term HbA1c (glycated haemoglobin) variability is associated with micro- and macrovascular complications in Type 2 diabetes (T2D). We explored prospective associations between HbA1c variability and serious infections, and how these vary by HbA1c level, age, sex and ethnicity. METHODS: 411,963 T2D patients in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink with ≥ 4 HbA1c measurements during 2011-14. Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HbA1c variability score (HVS) and average level, adjusting for confounders, and stratified by age, sex, ethnicity and average level. Attributable risk fractions (AF) were calculated using reference categories for variability (HVS < 20) and average level (42-48 mmol/mol). RESULTS: An increased infection risk (IRR > 1.2) was seen with even modest variability (HVS ≥ 20, 73 % of T2D patients), but only at higher average levels (≥64 mmol/mol, 27 % patients). Estimated AFs were markedly greater for variability than average level (17.1 % vs. 4.1 %). Associations with variability were greater among older patients, and those with lower HbA1c levels, but not observed among Black ethnicities. CONCLUSIONS: HbA1c variability between T2D patients' primary care visits appears to be associated with more serious infections than average level overall. Well-designed trials could test whether these associations are causal.

Impact of price reductions, subsidies, or financial incentives on healthy food purchases and consumption: a systematic review and meta-analysis.

Poor diets are a global concern and are linked with various adverse health outcomes. Healthier foods such as fruit and vegetables are often more expensive than unhealthy options. This study aimed to assess the effect of price reductions for healthy food (including fruit and vegetables) on diet. We performed a systematic review and meta-analysis on studies that looked at the effects of financial incentives on healthy food. Main outcomes were change in purchase and consumption of foods following a targeted price reduction. We searched electronic databases (MEDLINE, EconLit, Embase, Cinahl, Cochrane Library, and Web of Science), citations, and used reference screening to identify relevant studies from Jan 1, 2013, to Dec 20, 2021, without language restrictions. We stratified results by population targeted (low-income populations vs general population), the food group that the reduction was applied to (fruit and vegetables, or other healthier foods), and study design. Percentage price reduction was standardised to assess the effect in meta-analyses. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. 34 studies were eligible; 15 took place in supermarkets and eight took place in workplace canteens in high-income countries, and 21 were targeted at socioeconomically disadvantaged communities. Pooled analyses of 14 studies showed a price reduction of 20% resulted in increases in fruit and vegetable purchases by 16·62% (95% CI 12·32 to 20·91). Few studies had maintained the price reduction for over 6 months. In conclusion, price reductions can lead to increases in purchases of fruit and vegetables, potentially sufficient to generate health benefits, if sustained.

A matched cohort study evaluating the risks of infections in people with type 1 diabetes and their associations with glycated haemoglobin.

AIMS: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain. METHODS: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles. RESULTS: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol. CONCLUSIONS: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions.

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity.

BACKGROUND: People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB-treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at diagnosis. It is unknown whether this persists through treatment and contributes to the adverse outcomes. METHODS: Pulmonary TB patients recruited in South Africa, Indonesia and Romania were classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or TB-only, based on glycated haemoglobin concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood at diagnosis and intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Transcriptomic data were analysed by longitudinal mixed-model regression to identify whether genes were differentially expressed between clinical groups through time. Predictive models of TB-treatment response across groups were developed and cross-tested. RESULTS: Gene expression differed between TB and TB-DM patients at diagnosis and was modulated by TB treatment in all clinical groups but to different extents, such that differences remained in TB-DM relative to TB-only throughout. Expression of some genes increased through TB treatment, whereas others decreased: some were persistently more highly expressed in TB-DM and others in TB-only patients. Genes involved in innate immune responses, anti-microbial immunity and inflammation were significantly upregulated in people with TB-DM throughout treatment. The overall pattern of change was similar across clinical groups irrespective of diabetes status, permitting models predictive of TB treatment to be developed. CONCLUSIONS: Exacerbated transcriptome changes in TB-DM take longer to resolve during TB treatment, meaning they remain different from those in uncomplicated TB after treatment completion. This may indicate a prolonged inflammatory response in TB-DM, requiring prolonged treatment or host-directed therapy for complete cure. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes for use across populations.

Epidemiological impact of public health interventions against diabetes in Qatar: mathematical modeling analyses.

Aims: To predict the epidemiological impact of specific, and primarily structural public health interventions that address lifestyle, dietary, and commuting behaviors of Qataris as well as subsidies and legislation to reduce type 2 diabetes mellitus (T2DM) burden among Qataris. Methods: A deterministic population-based mathematical model was used to investigate the impact of public health interventions on the epidemiology of T2DM among Qataris aged 20-79 years, which is the age range typically used by the International Diabetes Federation for adults. The study evaluated the impact of interventions up to 2050, a three-decade time horizon, to allow for the long-term effects of different types of interventions to materialize. The impact of each intervention was evaluated by comparing the predicted T2DM incidence and prevalence with the intervention to a counterfactual scenario without intervention. The model was parameterized using representative data and stratified by sex, age, T2DM risk factors, T2DM status, and intervention status. Results: All intervention scenarios had an appreciable impact on reducing T2DM incidence and prevalence. A lifestyle management intervention approach, specifically applied to those who are categorized as obese and ≥35 years old, averted 9.5% of new T2DM cases by 2050. An active commuting intervention approach, specifically increasing cycling and walking, averted 8.5% of new T2DM cases by 2050. Enhancing consumption of healthy diets including fruits and vegetables, specifically a workplace intervention involving dietary modifications and an educational intervention, averted 23.2% of new T2DM cases by 2050. A subsidy and legislative intervention approach, implementing subsidies on fruits and vegetables and taxation on sugar-sweetened beverages, averted 7.4% of new T2DM cases by 2050. A least to most optimistic combination of interventions averted 22.8-46.9% of new T2DM cases by 2050, respectively. Conclusions: Implementing a combination of individual-level and structural public health interventions is critical to prevent T2DM onset and to slow the growing T2DM epidemic in Qatar.

Diabetes Mellitus and Tuberculosis Treatment Outcomes: Interaction Assessment Between Hyperglycemia and Human Immunodeficiency Virus in the State of Georgia, 2015-2020.

Background: Diabetes mellitus and human immunodeficiency virus (HIV) are independent risk factors for poor outcomes among people with tuberculosis (TB). To date, information on the joint impact of diabetes and HIV on TB outcomes is limited. We aimed to estimate (1) the association between hyperglycemia and mortality and (2) the effect of joint exposure to diabetes and HIV on mortality. Methods: We conducted a retrospective cohort study among people with TB in the state of Georgia between 2015 and 2020. Eligible participants were 16 or older, did not have a previous TB diagnosis, and were microbiologically confirmed or clinical cases. Participants were followed during TB treatment. Robust Poisson regression was used to estimate risk ratios for all-cause mortality. Interaction between diabetes and HIV was assessed on the additive scale using the attributable proportion and on the multiplicative scale with product terms in regression models. Results: Of 1109 participants, 318 (28.7%) had diabetes, 92 (8.3%) were HIV positive, and 15 (1.4%) had diabetes and HIV. Overall, 9.8% died during TB treatment. Diabetes was associated with an increased risk of death among people with TB (adjusted risk ratio [aRR] = 2.59; 95% confidence interval [CI], 1.62-4.13). We estimated that 26% (95% CI, -43.4% to 95.0%) of deaths among participants with diabetes mellitus and HIV were due to biologic interaction. Conclusions: Diabetes alone and co-occurring diabetes and HIV were associated with an increased risk of all-cause mortality during TB treatment. These data suggest a potential synergistic effect between diabetes and HIV.

Evaluating Ethnic Variations in the Risk of Infections in People With Prediabetes and Type 2 Diabetes: A Matched Cohort Study.

OBJECTIVE: People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia ("prediabetes"). RESEARCH DESIGN AND METHODS: We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18-90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015-2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders. RESULTS: People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51-1.52) and hospitalizations (IRR 1.91, 1.90-1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age <50) experienced a greater relative risk. Adjustment for socioeconomic deprivation, smoking, and comorbidity attenuated associations, but IRRs remained similar by ethnicity. For prediabetes, a significant but smaller risk was observed (primary care IRR 1.35, 95% CI 1.34-1.36; hospitalization IRR 1.33, 1.31-1.35). These were similar within each ethnicity for primary care infections, but less consistent for infection-related hospitalizations. CONCLUSIONS: The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment.

BACKGROUND: Globally, the tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment outcome early after diagnosis, especially in TB-DM patients, would allow early treatment adaptation for individuals and may improve global TB control. METHODS: Samples were collected in a longitudinal cohort study of adult TB patients from South Africa (n  =  94) and Indonesia (n  =  81), who had concomitant DM (n  =  59), intermediate hyperglycaemia (n  =  79) or normal glycaemia/no DM (n  =  37). Treatment outcome was monitored, and patients were categorized as having a good (cured) or poor (failed, recurrence, died) outcome during treatment and 12 months follow-up. Whole blood transcriptional profiles before, during and at the end of TB treatment were characterized using unbiased RNA-Seq and targeted gene dcRT-MLPA. FINDINGS: We report differences in whole blood transcriptome profiles, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature distinguished patients with a good TB treatment outcome from patients with a poor TB treatment outcome at diagnosis (AUC = 0·815) or two weeks (AUC = 0·834) after initiation of TB treatment, respectively. High accuracy was obtained by cross-validating this signature in an external cohort (AUC = 0·749). INTERPRETATION: These findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM. FUNDING: The research leading to these results, as part of the TANDEM Consortium, received funding from the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038). The research leading to the results presented in the Indian validation cohort was supported by Research Council of Norway Global Health and Vaccination Research (GLOBVAC) projects: RCN 179342, 192534, and 248042, the University of Bergen (Norway).

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP). METHODS: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM. DISCUSSION: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control. TRIAL REGISTRATION: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

Impact of diabetes mellitus on tuberculosis epidemiology in Indonesia: A mathematical modeling analysis.

We investigated and forecasted the impact of diabetes mellitus (DM) on tuberculosis (TB) epidemiology in Indonesia between 2020 and 2050. A recently-developed age-structured TB-DM dynamic mathematical model was utilized to assess the impact of DM on TB epidemiology. Model parameters were informed by systematic reviews and meta-analyses. Sensitivity and uncertainty analyses were conducted to assess robustness of predictions. The proportion of TB incident cases attributed to DM increased from 18.8% (95% uncertainty interval (UI): 12.6%-24.3%) in 2020, to 20.9% (95% UI: 14.7%-27.1%) in 2030, and 25.8% (95% UI: 17.7%-32.2%) in 2050. The proportion of TB-related deaths attributed to DM increased from 24.3% (95% UI: 18.7%-29.1%) in 2020, to 27.7% (95% UI: 22.4%-32.4%) in 2030, and 34.3% (95% UI: 27.6%-38.0%) in 2050. Most of the impact of DM on TB transmission has risen because of faster progression to TB disease, increased risk of reinfection, and increased infectiousness, with higher bacterial loads. Sensitivity and uncertainty analyses affirmed the predictions. TB-DM synergy is projected to increase in Indonesia over the next three decades with DM becoming a major driver of TB incidence and deaths. Joint TB-DM management and programs could offer significant reductions in TB incidence and mortality, making post-2015 End TB targets more feasible.

Tuberculosis risk among people with diabetes mellitus in Sub-Saharan Africa: A systematic review.

OBJECTIVES: People with diabetes mellitus (DM) have a higher tuberculosis (TB) risk, but the evidence from sub-Saharan Africa (SSA) was scarce until recently and not included in earlier global summaries. Therefore, this systematic review aims to determine the risk of active TB disease among people with DM in SSA and whether HIV alters this association. METHODS: Medline, Embase, CINAHL, Web of Science, Global Health and African Index Medicus were searched between January 1980 and February 2021. Cohort, case-control and cross-sectional studies from SSA, which assessed the association between DM and active TB, were included if adjusted for age. Two researchers independently assessed titles, abstracts, full texts, extracted data and assessed the risk of bias. Estimates for the association between DM and TB were summarised using a random effects meta-analysis. PROSPERO: CRD42021241743. RESULTS: Nine eligible studies were identified, which reported on 110,905 people from 5 countries. Individual study odds ratios (OR) of the TB-DM association ranged from 0.88 (95% CI 0.17-4.58) to 10.7 (95% CI 4.5-26). The pooled OR was 2.77 (95% CI 1.90-4.05). High heterogeneity was reduced in sensitivity analysis (from I2  = 57% to I2  = 6.9%), by excluding one study which ascertained DM by HbA1c. Risk of bias varied widely between studies, especially concerning the way in which DM status was determined. CONCLUSIONS: There is a strong positive association between DM and active TB in SSA. More research is needed to determine whether HIV, a key risk factor for TB in SSA, modifies this relationship.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

A systematic review of interventions to promote physical activity in six Gulf countries.

Physical activity (PA) levels are low in Gulf Cooperation Council countries (GCC; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates). We carried out a systematic review (PROSPERO registration number 131817) to assess the effect of interventions to increase PA levels in this region. We also assessed their effects on anthropometry and cardiovascular risk. A systematic search of six databases (Medline, EMBASE, SPORTDiscus, CINAHL, Cochrane, Web of Science) was performed to identify randomized and non-randomized intervention studies performed in adults and children published between January 1985 and November 2020. We included studies published in English or Arabic, and included PA interventions regardless of setting, delivery, and duration. The primary outcomes were changes in PA duration and intensity. Secondary outcomes included anthropometric measures (e.g., weight, body mass index) and cardiovascular risk profiles (e.g., lipid measures, blood glucose). Two independent reviewers screened studies in accordance with pre-determined criteria, extracted data, assessed risk of bias (Cochrane Risk of Bias 2 and Newcastle Ottawa Scale) and undertook a narrative synthesis. From 13,026 records identified, 14 studies were included. Nine studies focussed exclusively on changing PA behaviour, resulting in statistically significant increases in step count ranging from an additional 757 steps/day (95% confidence interval [CI] 0-1,513) to 3,853 steps/day (95% CI 3,703-4,002). Five identified studies were multi-component lifestyle interventions, targeting people at higher risk (due to obesity or type 2 diabetes). Evidence for increases in PA from multi-component studies was limited, although improvements were seen in outcomes e.g. body weight and blood lipid levels. In conclusion, relatively few studies have focussed on changing PA behaviour, despite the urgent need in the GCC. Limited evidence suggested that pedometer-based programmes encouraging step counting and walking were effective in promoting PA, at least in the short term. Policies to roll out such interventions should be implemented and evaluated.

The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial.

AIMS: Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM. METHODS: In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point. RESULTS: We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure. CONCLUSION: Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.

Hand-washing promotion for preventing diarrhoea.

BACKGROUND: Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. OBJECTIVES: To assess the effects of hand-washing promotion interventions on diarrhoeal episodes in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases, the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), and metaRegister of Controlled Trials (mRCT) on 8 January 2020, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: Individually-randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand-washing interventions on diarrhoea episodes in children and adults with no intervention. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility, extracted data, and assessed risks of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, we pooled incidence rate ratios (IRRs) using the generic inverse variance method and a random-effects model with a 95% confidence interval (CI). We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 29 RCTs: 13 trials from child day-care centres or schools in mainly high-income countries (54,471 participants), 15 community-based trials in LMICs (29,347 participants), and one hospital-based trial among people with AIDS in a high-income country (148 participants). All the trials and follow-up assessments were of short-term duration. Hand-washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevent around one-third of diarrhoea episodes in high-income countries (incidence rate ratio (IRR) 0.70, 95% CI 0.58 to 0.85; 9 trials, 4664 participants, high-certainty evidence) and may prevent a similar proportion in LMICs, but only two trials from urban Egypt and Kenya have evaluated this (IRR 0.66, 95% CI 0.43 to 0.99; 2 trials, 45,380 participants; low-certainty evidence). Only four trials reported measures of behaviour change, and the methods of data collection were susceptible to bias. In one trial from the USA hand-washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; 3 trials, 1845 participants; low-certainty evidence). Hand-washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (IRR 0.71, 95% CI 0.62 to 0.81; 9 trials, 15,950 participants; moderate-certainty evidence). However, six of these nine trials were from Asian settings, with only one trial from South America and two trials from sub-Saharan Africa. In seven trials, soap was provided free alongside hand-washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: RR 0.66, 95% CI 0.58 to 0.75; 7 trials, 12,646 participants; education only: RR 0.84, 95% CI 0.67 to 1.05; 2 trials, 3304 participants). There was increased hand washing at major prompts (before eating or cooking, after visiting the toilet, or cleaning the baby's bottom) and increased compliance with hand-hygiene procedure (behavioural outcome) in the intervention groups compared with the control in community trials (data not pooled: 4 trials, 3591 participants; high-certainty evidence). Hand-washing promotion for the one trial conducted in a hospital among a high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (mean difference -1.68, 95% CI -1.93 to -1.43; 1 trial, 148 participants; moderate-certainty evidence). Hand-washing frequency increased to seven times a day in the intervention group versus three times a day in the control arm in this hospital trial (1 trial, 148 participants; moderate-certainty evidence). We found no trials evaluating the effects of hand-washing promotions on diarrhoea-related deaths or cost effectiveness. AUTHORS' CONCLUSIONS: Hand-washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. The included trials do not provide evidence about the long-term impact of the interventions.

ANTECEDENTES: La diarrea es responsable de 1 800 000 muertes de niños en los países de ingresos bajos y medios (PIBM). Una de las estrategias identificadas para prevenir la diarrea es el lavado de manos. OBJETIVOS: Evaluar los efectos de las intervenciones de promoción del lavado de manos sobre los episodios de diarrea en niños y adultos. MÉTODOS DE BÚSQUEDA: El 8 de enero de 2020 se realizaron búsquedas en CENTRAL, MEDLINE, Embase, en otras nueve bases de datos, la Plataforma de registros internacionales de ensayos clínicos (ICTRP) de la Organización Mundial de la Salud (OMS) y el metaRegister of Controlled Trials (mRCT), además de comprobación de referencias, búsqueda de citas y contacto con los autores de los estudios para identificar estudios adicionales. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) individuales y por conglomerados que compararon los efectos de las intervenciones de lavado de manos sobre los episodios de diarrea en niños y adultos, con ninguna intervención. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron la elegibilidad de los ensayos, extrajeron los datos y evaluaron los riesgos de sesgo. Los análisis se estratificaron por guarderías infantiles o escuelas, comunidad y contextos hospitalarios. Cuando fue conveniente, se agruparon los cocientes de la tasa de incidencia (CTI) según el método de la varianza inversa genérica y un modelo de efectos aleatorios con un intervalo de confianza (IC) del 95%. Se utilizaron los criterios GRADE para evaluar la certeza de la evidencia. RESULTADOS PRINCIPALES: Se incluyeron 29 ECA: 13 ensayos de guarderías infantiles o escuelas en países principalmente de ingresos altos (54 471 participantes), 15 ensayos comunitarios en PIMB (29 347 participantes) y un ensayo hospitalario en pacientes con sida en países de ingresos altos (148 participantes). Todos los ensayos y evaluaciones de seguimiento fueron a corto plazo. La promoción del lavado de manos (actividades educativas, a veces con la provisión de jabón) en las guarderías infantiles o las escuelas previene alrededor de un tercio de los episodios de diarrea en los países de ingresos altos (cociente de tasa de incidencia [CTI] 0,70; IC del 95%: 0,58 a 0,85; nueve ensayos, 4664 participantes, evidencia de certeza alta), y podría prevenir una proporción similar en los PIMB, pero solo dos ensayos en zonas urbanas de Egipto y Kenya lo han evaluado (CTI 0,66; IC del 95%: 0,43 a 0,99; dos ensayos, 45 380 participantes, evidencia de certeza baja). Solo cuatro ensayos informaron sobre medidas de cambio en el comportamiento y los métodos de recopilación de datos fueron susceptibles de sesgo. En un ensayo de los EE.UU. se informó de que el comportamiento de lavado de manos mejoró; y en el ensayo de Kenya que proporcionó jabón gratuito, el lavado de manos no aumentó, pero sí el uso de jabón (datos no agrupados; tres ensayos, 1845 participantes, evidencia de certeza baja). La promoción del lavado de manos entre las comunidades en los PIMB probablemente previene alrededor de una cuarta parte de los episodios de diarrea (CTI 0,71; IC del 95%: 0,62 a 0,81; nueve ensayos, 15 950 participantes, evidencia de calidad moderada). Sin embargo, seis de estos nueve ensayos procedían de entornos asiáticos, y solo hubo un ensayo en América del Sur y dos en el África subsahariana. En siete ensayos, el jabón se suministró gratuitamente junto con la educación para el lavado de manos, y el tamaño del efecto medio general fue mayor que en los dos ensayos que no suministraron jabón (jabón suministrado: RR 0,66; IC del 95%: 0,58 a 0,75; siete ensayos, 12 646 participantes; solo educación: RR 0,84; IC del 95%: 0,67 a 1,05; dos ensayos, 3304 participantes). Hubo un aumento del lavado de manos en los momentos más importantes (antes de comer o cocinar, después de ir al baño o de limpiar el trasero del niño), y un aumento en el cumplimiento del procedimiento de higiene de las manos (resultado conductual) en los grupos de intervención, en comparación el control, en los ensayos comunitarios (datos no agrupados: cuatro ensayos, 3591 participantes; evidencia de certeza alta). La promoción del lavado de manos en el único ensayo realizado en un hospital en una población de alto riesgo mostró una reducción significativa de los episodios medios de diarrea (1,68 menos) en el grupo de intervención (diferencia de medias ­1,68; IC del 95%: ­1,93 a ­1,43; un ensayo, 148 participantes, evidencia de certeza moderada). En este ensayo hospitalario la frecuencia del lavado de manos aumentó hasta siete veces al día en el grupo de intervención versus tres veces al día en el grupo control (un ensayo, 148 participantes, evidencia de certeza moderada). No se encontraron ensayos que evaluaran los efectos de la promoción del lavado de manos sobre las muertes relacionadas con la diarrea ni el coste­efectividad. CONCLUSIONES DE LOS AUTORES: La promoción del lavado de manos probablemente reduce los episodios de diarrea en las guarderías infantiles de los países de altos ingresos y en las comunidades que viven en los PIMB, en aproximadamente el 30%. Los ensayos incluidos no aportan evidencia sobre el efecto a largo plazo de esta intervención.

The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice.

Diabetes Mellitus increases the risk of developing Tuberculosis (TB) disease by about three times; it also doubles the risk of death during TB treatment and other poor TB treatment outcomes. Diabetes may increase the risk of latent infection with Mycobacterium tuberculosis (LTBI), but the magnitude of this effect is less clear. Whilst this syndemic has received considerable attention, most of the published research has focussed on screening for undiagnosed diabetes in TB patients or observational follow-up of TB treatment outcomes by diabetes status. There are thus substantial research and policy gaps, particularly with regard to prevention of TB disease in people with diabetes and management of patients with TB-diabetes, both during TB treatment and after successful completion of TB treatment, when they likely remain at high risk of TB recurrence, mortality from TB and cardiovascular disease. Potential strategies to prevent development of TB disease might include targeted vaccination programmes, screening for LTBI and preventive therapy among diabetes patients or, perhaps ideally, improved diabetes management and prevention. The cost-effectiveness of each of these, and in particular how each strategy might compare with targeted TB prevention among other population groups at higher risk of developing TB disease, is also unknown. Despite research gaps, clinicians urgently need practical management advice and more research evidence on the choice and dose of different anti-diabetes medication and effective medical therapies to reduce cardiovascular risks (statins, anti-hypertensives and aspirin). Substantial health system strengthening and integration may be needed to prevent these at risk patients being lost to care at the end of TB treatment.

A diabetes risk score for Qatar utilizing a novel mathematical modeling approach to identify individuals at high risk for diabetes.

We developed a diabetes risk score using a novel analytical approach and tested its diagnostic performance to detect individuals at high risk of diabetes, by applying it to the Qatari population. A representative random sample of 5,000 Qataris selected at different time points was simulated using a diabetes mathematical model. Logistic regression was used to derive the score using age, sex, obesity, smoking, and physical inactivity as predictive variables. Performance diagnostics, validity, and potential yields of a diabetes testing program were evaluated. In 2020, the area under the curve (AUC) was 0.79 and sensitivity and specificity were 79.0% and 66.8%, respectively. Positive and negative predictive values (PPV and NPV) were 36.1% and 93.0%, with 42.0% of Qataris being at high diabetes risk. In 2030, projected AUC was 0.78 and sensitivity and specificity were 77.5% and 65.8%. PPV and NPV were 36.8% and 92.0%, with 43.0% of Qataris being at high diabetes risk. In 2050, AUC was 0.76 and sensitivity and specificity were 74.4% and 64.5%. PPV and NPV were 40.4% and 88.7%, with 45.0% of Qataris being at high diabetes risk. This model-based score demonstrated comparable performance to a data-derived score. The derived self-complete risk score provides an effective tool for initial diabetes screening, and for targeted lifestyle counselling and prevention programs.

Forecasting the type 2 diabetes mellitus epidemic and the role of key risk factors in Oman up to 2050: Mathematical modeling analyses.

AIMS/INTRODUCTION: To investigate and forecast type 2 diabetes mellitus epidemic, its related risk factors and cost in Oman by 2050. MATERIALS AND METHODS: An age-structured mathematical model was used to characterize type 2 diabetes mellitus epidemiology and trends in Oman between 1990 and 2050. The model was parametrized using current and quality data, including six nationally representative population-based epidemiological surveys for type 2 diabetes mellitus and its key risk factors. RESULTS: The projected type 2 diabetes mellitus prevalence increased from 15.2% in 2020 to 23.8% in 2050. The prevalence increased from 16.8 and 13.8% in 2020 among women and men to 26.3 and 21.4% in 2050, respectively. In 2020, 190,489 Omanis were living with type 2 diabetes mellitus compared with 570,227 in 2050. The incidence rate per 1,000 person-years changed from 8.3 in 2020 to 12.1 in 2050. Type 2 diabetes mellitus' share of Oman's national health expenditure grew by 36% between 2020 and 2050 (from 21.2 to 28.8%). Obesity explained 56.7% of type 2 diabetes mellitus cases in 2020 and 71.4% in 2050, physical inactivity explained 4.3% in 2020 and 2.7% in 2050, whereas smoking accounted for <1% of type 2 diabetes mellitus cases throughout 2020-2050. Sensitivity and uncertainty analyses affirmed these predictions. CONCLUSIONS: The type 2 diabetes mellitus epidemic in Oman is expected to increase significantly over the next three decades, consuming nearly one-third of the national health expenditure. The type 2 diabetes mellitus burden is heavily influenced by obesity. Interventions targeting this single risk factor should be a national priority to reduce and control the burden of type 2 diabetes mellitus in Oman.