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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 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.

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 2015-2020. 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 (aRR = 2.59, 95% CI: 1.62, 4.13). We estimated that 26% (95% CI: -43.4%, 95.0%) of deaths among participants with DM 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.

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.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.CRD42021241743.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 IThere 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.

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.

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 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.

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.govNCT04600167. Registered on 23 October 2020

BackgroundUsing a previously developed and validated mathematical model, we predicted future prevalence of type 2 diabetes mellitus (T2DM) and major modifiable risk factors (obesity, physical inactivity and smoking) stratified by age and sex in Turkey up to the year 2050.MethodsOur deterministic compartmental model fitted nationally representative demographic and risk factor data simultaneously for Turkish adults (aged 20–79) between 1997 and 2017, then estimated future trends. Our novel approach explored the impact of future obesity trends on these projections, specifically modelling (1) a gradual fall in obesity in women after the year 2020 until it equalled the age-specific levels seen in men and (2) cessation of the rise in obesity after 2020.ResultsT2DM prevalence is projected to rise from an estimated 14.0% (95% uncertainty interval (UI) 12.8% to 16.0%) in 2020 to 18.4% (95% UI 16.9% to 20.9%) by 2050; 19.7% in women and 17.2% in men by 2050; reflecting high levels of obesity (39.7% for women and 22.0% for men in 2050). Overall, T2DM prevalence could be reduced by about 4% if obesity stopped rising after 2020 or by 12% (22% in women) if obesity prevalence among women could be lowered to equal that of men. The higher age-specific obesity prevalence among women resulted in 2 076 040 additional women developing T2DM by the year 2050.ConclusionT2DM is common in Turkey and will remain so. Interventions and policies targeting the high burden of obesity (and low physical activity levels), particularly in women, could significantly impact future disease burdens.

Background Diabetes mellitus (DM) patients are three times more likely to develop tuberculosis (TB) than the general population. Active TB screening in people with DM is part of a bidirectional approach. The aim of this study was to conduct pragmatic active TB screening among DM patients in four countries to inform policy. Methods DM patients were recruited in Indonesia (n=809), Peru (n=600), Romania (n=603) and South Africa (n=51). TB cases were diagnosed using an algorithm including clinical symptoms and chest X-ray. Presumptive TB patients were examined with sputum smear and culture. Results A total of 171 (8.3%) individuals reported ever having had TB (South Africa, 26%; Indonesia, 12%; Peru, 7%; Romania, 4%), 15 of whom were already on TB treatment. Overall, 14 (0.73% [95% confidence interval 0.40 to 1.23]) TB cases were identified from screening. Poor glucose control, smoking, lower body mass index, education and socio-economic status were associated with newly diagnosed/current TB. Thirteen of the 14 TB cases diagnosed from this screening would have been found using a symptom-based approach. Conclusions These data support the World Health Organization recommendation for routine symptom-based screening for TB in known DM patients in high TB-burden countries. DM patients with any symptoms consistent with TB should be investigated and diagnostic tools should be easily accessible.

Background Deficiencies in airway management skills and judgement contribute to poor outcomes. Airway management practice guidelines emphasise the importance of education. Little is known about the global uptake of guidelines, availability of equipment, provision of training, assessment of skills, and confidence with procedures. Methods We devised a survey to examine these issues. Initially, 24 127 anaesthetists were questioned in New Zealand, Canada, South Africa, UK, India, and Germany, representing the home countries of the members of the Worldwide Airway Meeting (2015) Education Group; however, the survey could be forwarded to others. The survey was open for a maximum of 90 days. Results We received 4948 fully or partially completed surveys from 61 countries: 33 high-income and 28 middle- or low-income countries. Most respondents were consultants (77.2%, n=4948), and the remainder trainees, with a male/female ratio of 1.8:1 (3105 males, n=4866). Of those responding, 1358 (76.6%, n=1798) were members of an airway interest group. Most respondents (91.3% of 2910) agreed with assessment of airway skills, fewer (2237; 59.7%, n=3750) reported requiring airway training for completion of training, and only 810 (33.6%, n=2408) reported it as a requirement for continuing medical education. Reported confidence was lowest for awake tracheal intubation, front-of-neck access, and retrograde intubation. Conclusions Global training is variable in its delivery and necessity. Confidence is limited in potentially life-saving techniques. The desire for assessment appears universal and may improve standards, but in resource- or time-limited environments this will be challenging.

BackgroundPeople 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 TB diagnosis. It is unknown whether this persists through treatment, potentially underlying adverse outcomes.MethodsPulmonary TB patients were recruited in South Africa, Indonesia and Romania, and classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or uncomplicated TB, based on glycated haemoglobin (HbA1c) concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood samples collected at diagnosis and at regular intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification.ResultsGene expression was modulated by TB treatment in all groups but to different extents, such that differences remained in people with TB-DM relative to TB-only throughout, including genes involved in innate responses, anti-microbial immunity and the inflammasome. People with prediabetes or with TB-related hyperglycaemia had gene expression more similar to people with TB-DM than TB-only throughout treatment. The overall pattern of change was similar across clinical groups irrespective of glycaemic index, permitting models predictive of TB treatment to be developed.ConclusionsThe exacerbated transcriptome changes seen in TB-DM take longer to resolve during TB treatment, indicating that prolonged treatment or host-directed therapy may be needed to improve TB treatment outcomes. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes to be useful across populations.Key PointsHost blood transcriptomes are altered in tuberculosis, and further altered with diabetes co-morbidity. We have shown that there is similar resolution of transcriptomes through treatment, but with differing magnitude and kinetics in TB patients with or without diabetes.

This work was supported by the University of Nicosia Medical School (internal funding)., Achilleos S, Quattrocchi A, Gabel J, Heraclides A, Kolokotroni O, Constantinou C, Pagola Ugarte M, Nicolaou N, Rodriguez-Llanes JM, Bennett CM, Bogatyreva E, Schernhammer E, Zimmermann C, Costa AJL, Lobato JCP, Fernandes NM, Semedo-Aguiar AP, Jaramillo Ramirez GI, Martin Garzon OD, Mortensen LH, Critchley JA, Goldsmith LP, Denissov G, Rüütel K, Le Meur N, Kandelaki L, Tsiklauri S, O'Donnell J, Oza A, Kaufman Z, Zucker I, Ambrosio G, Stracci F, Hagen TP, Erzen I, Klepac P, Arcos González P, Fernández Camporro Á, Burström B, Pidmurniak N, Verstiuk O, Huang Q, Mehta NK, Polemitis A, Charalambous A, Demetriou CA.

ObjectiveContemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes.MethodsWe systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications.ResultsIn total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=97.4%), respectively.ConclusionAttainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa.

IntroductionWe aimed to characterize and forecast type 2 diabetes mellitus (T2DM) disease burden between 2021 and 2050 in Qatar where 89% of the population comprises expatriates from over 150 countries.Research design and methodsAn age-structured mathematical model was used to forecast T2DM burden and the impact of key risk factors (obesity, smoking, and physical inactivity). The model was parametrized using data from T2DM natural history studies, Qatar’s 2012 STEPwise survey, the Global Health Observatory, and the International Diabetes Federation Diabetes Atlas, among other data sources.ResultsBetween 2021 and 2050, T2DM prevalence increased from 7.0% to 14.0%, the number of people living with T2DM increased from 170 057 to 596 862, and the annual number of new T2DM cases increased from 25 007 to 45 155 among those 20–79 years of age living in Qatar. Obesity prevalence increased from 8.2% to 12.5%, smoking declined from 28.3% to 26.9%, and physical inactivity increased from 23.1% to 26.8%. The proportion of incident T2DM cases attributed to obesity increased from 21.9% to 29.9%, while the contribution of smoking and physical inactivity decreased from 7.1% to 6.0% and from 7.3% to 7.2%, respectively. The results showed substantial variability across various nationality groups residing in Qatar—for example, in Qataris and Egyptians, the T2DM burden was mainly due to obesity, while in other nationality groups, it appeared to be multifactorial.ConclusionsT2DM prevalence and incidence in Qatar were forecasted to increase sharply by 2050, highlighting the rapidly growing need of healthcare resources to address the disease burden. T2DM epidemiology varied between nationality groups, stressing the need for prevention and treatment intervention strategies tailored to each nationality.

OBJECTIVE Diabetes guidelines focus on target glycated hemoglobin (HbA1c) levels. Long-term variability in HbA1c may be predictive of hospitalization or mortality, but its importance at different average levels or trajectories is unclear. RESEARCH DESIGN AND METHODS Using English primary care data, 58,832 patients with type 2 diabetes had HbA1c average (mean of annual means), variability (coefficient of variation), and trajectory (annual regression slope) estimated during 2006–2009. Hazard ratios (HRs) for mortality and emergency hospitalization during 2010–2015, with adjustment for age, sex, smoking, BMI, duration of diabetes, and deprivation, were estimated using Cox regression. The simultaneous impact of HbA1c average, variability, and trajectory was estimated using percentiles. RESULTS In mutually adjusted models, HbA1c variability showed a consistent dose-response relationship with all-cause mortality, while average level was only important among individuals in the highest or lowest 10% of the distribution, and trajectory had no independent effect. Individuals with the most unstable HbA1c (top 10%) were almost twice as likely to die (HR 1.93 [95% CI 1.72–2.16]) than were those with the most stable (bottom 10%)—an association attenuated but not explained by hypoglycemia. For emergency hospitalizations, similar trends were seen except for coronary artery disease (CAD) and ischemic stroke (IS), where increasing average rather than variability was predictive. CONCLUSIONS HbA1c variability was strongly associated with overall mortality and emergency hospitalization and not explained by average HbA1c or hypoglycemic episodes. Only for CAD and IS hospitalizations was no association found, with average HbA1c strongly predictive. Targets should focus on both stability and absolute level of HbA1c.

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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.

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., Plain language summary Does encouraging people to wash their hands stop them having diarrhoea? Key messages Encouraging hand washing probably reduces the number of times children have diarrhoea, by around 30%, in communities in low‐ to middle‐income countries and in child‐care centres in high‐income countries. We did not find evidence about the long‐term effects of hand‐washing programmes. What causes diarrhoea? ‘Diarrhoea’ is the name for frequent bowel movements or the passing of unusually soft or watery faeces. Infections of the gut by bacteria, viruses, or parasites commonly cause diarrhoea, and are mostly spread through water contaminated with faeces. The symptoms of diarrhoea usually improve in a couple of days. However, in severe or long‐lasting diarrhoea, too much water, salts, and nutrients may be lost from the body. This loss can cause dehydration and even death. Diarrhoea is a leading cause of death and sickness among children under five years of age. Preventing diarrhoea Most deaths associated with diarrhoea are caused by pathogens acquired as a result of unsafe drinking water, poor sanitary conditions, and lack of hygiene. Washing hands with soap and water removes the bacteria, viruses, and parasites that cause disease. Programmes and activities encouraging people to wash their hands have been developed for use in communities and schools, including hygiene training, posters, leaflets, comic books, songs, and drama. Why we did this Cochrane Review We know that hand washing at appropriate times can prevent diarrhoea, but we do not know how best to encourage the practice. We wanted to find out if programmes and activities that had been studied for this purpose were effective at increasing hand washing and reducing diarrhoea. What did we do? We searched for studies that investigated the use of programmes to encourage hand washing in communities, day‐care centres, schools, hospitals, and households. We were interested in whether taking part in the programmes affected the number of times people in the study reported having diarrhoea. We looked for studies in which the treatments people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a treatment. Search date We included evidence published up to 8 January 2020. What we found We found 29 studies: 13 studies (in 54,471 people) took place in child day‐care centres or schools in mainly high‐income countries; 15 studies (in 29,347 people) were community‐based in low‐ to middle‐income countries; and 1 study (in 148 people) was hospital‐based. The studies looked at the effects of hand‐washing programmes on the number of times people in the study reported having diarrhoea. The effects of the programmes were followed for four months to one year. No studies reported the effects of hand‐washing programmes on how many people died from diarrhoea, how many children under five years of age died (of any cause), or whether the benefits associated with the programme outweighed any extra costs. What are the results of our review? All studies compared the effects of programmes to encourage hand washing with not having any programmes about hand washing. In child‐care centres and schools: in high‐income countries, encouraging hand washing reduced the number of times children had diarrhoea (9 studies, 4664 children); and in low‐ to middle‐income countries may have reduced the number of times children had diarrhoea (2 studies, 45,380 children). In communities in low‐ to middle‐income countries, encouraging hand washing probably reduced the number of times children (up to 15 years of age) had diarrhoea (9 studies,; 15,950 children). In hospitalized adults with AIDS, encouraging hand washing probably reduced the number of times they had diarrhoea and probably improved hand‐washing behaviour (washing hands more often) over one year of follow‐up (1 study, 148 people). How reliable are these results? We are confident that, in high‐income countries, hand‐washing programmes in schools and child‐care centres reduced the number of times children had diarrhoea. This result is unlikely to change with more evidence. We are less confident about our result for low‐ to middle‐income countries, which is based on a small number of studies and might or might not change with more evidence. We are moderately confident about our results for children in communities and in hospitalized adults with AIDS. These results might change if more evidence becomes available.

Contains fulltext : 238090.pdf (Publisher’s version ) (Open Access) 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.

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.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.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.Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.

We aimed to characterize the type 2 diabetes mellitus (T2DM) epidemic and the role of key risk factors in Jordan between 1990–2050, and to forecast the T2DM-related costs. A recently-developed population-level T2DM mathematical model was adapted and applied to Jordan. The model was fitted to six population-based survey data collected between 1990 and 2017. T2DM prevalence was 14.0% in 1990, and projected to be 16.0% in 2020, and 20.6% in 2050. The total predicted number of T2DM cases were 218,326 (12,313 were new cases) in 1990, 702,326 (36,941 were new cases) in 2020, and 1.9 million (79,419 were new cases) in 2050. Out of Jordan’s total health expenditure, 19.0% in 1990, 21.1% in 2020, and 25.2% in 2050 was forecasted to be spent on T2DM. The proportion of T2DM incident cases attributed to obesity was 55.6% in 1990, 59.5% in 2020, and 62.6% in 2050. Meanwhile, the combined contribution of smoking and physical inactivity hovered around 5% between 1990 and 2050. Jordan’s T2DM epidemic is predicted to grow sizably in the next three decades, driven by population ageing and high and increasing obesity levels. The national strategy to prevent T2DM needs to be strengthened by focusing it on preventive interventions targeting T2DM and key risk factors.

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, The prevalence of type 2 diabetes mellitus in Oman was projected to grow by 57% by 2050, whereas the incidence was projected to grow by 200% by 2050. By 2050, type 2 diabetes mellitus will consume 30% of Oman’s health expenditure. The type 2 diabetes mellitus epidemic in Oman is driven by the high obesity level.

Background Most adults do not meet the recommended intake of five portions per day of fruit and vegetables (F&V) in England, but economic analyses of structural policies to change diet are sparse. This study aimed to estimate (1) the health and economic burden attributable to the low intake of fruit and vegetables (F&V) by English adults, and (2) the cost-effectiveness of three policies promoting consumption of F&V in England - a universal 10% subsidy, a targeted 30% subsidy for low-income households, and a nationwide social marketing campaign (SMC). Methods Using published data from official statistics and meta-epidemiological studies, we estimated the deaths, years-of-life lost (YLL), and the healthcare costs attributable to consumption of F&V below the recommended five portions per day by English adults. Then, we estimated the cost-effectiveness from governmental and societal perspectives of three policies. Results Low consumption of F&V accounted for 16,321 [10,091-23,516] deaths and 238,767 [170,350-311,651] YLL due to cardiovascular diseases, type 2 diabetes and cancer in England in 2017, alongside £705,951 [398,761-1,061,559] million in healthcare costs. From a societal perspective, the incremental cost-effectiveness ratios were £22,891 [22,300-25,079], £16,860 [15,589-19,763], and £25,683 [25,237-28,671] per life-year saved for the universal subsidy, targeted subsidy and SMC, respectively. At a threshold of £20,000 per life-year saved, the likelihood that the universal subsidy, the targeted subsidy and the SMC were cost-effective was 84%, 19% and 5%, respectively. The targeted subsidy was the only policy that would also reduce inequalities. Conclusions Both a SMC and subsidies can significantly increase consumption of F&V and reduce the attributable burden of disease and healthcare costs, but their cost-effectiveness varies substantially. A targeted subsidy to low-income households is most likely cost-effective and can additionally reduce inequalities. Key messages Low intake of fruit and vegetables accounts for a substantial number of deaths and years of life lost and represents a heavy burden for the healthcare system in England. From a societal perspective, a targeted subsidy to low-income households was most likely cost-effective and it would reduce inequalities.

IntroductionPrevalence of overweight, obesity and diabetes are high and rising across the Gulf Cooperation Council (GCC) countries (Oman, Bahrain, Kuwait, Qatar, Saudi Arabia and the United Arab Emirates). In parallel, physical activity (PA) levels are low relative to international standards. PA aids weight control and reduces risk of non-communicable diseases including diabetes and cardiovascular disease. It is likely interventions developed elsewhere will not translate to GCC countries due to unique environmental, social and cultural factors. This protocol is for a systematic review assessing the efficacy of interventions promoting PA within GCC countries among generally healthy adults and children. The primary outcome of interest is change in objectively measured or self-reported PA levels, the secondary outcomes of interest are changes in anthropometry or chronic disease risk factors (eg, blood pressure). Interventions will be compared with no intervention or those of differing PA intensity or duration. The relationships between PA change and the following will be assessed: intervention intensity or duration, season in which intervention occurs, sex, age, nationality and sustainability over time.Methods and analysisA systematic search strategy will identify indexed publications on the efficacy of interventions promoting PA. Randomised controlled trials and quasi-experimental studies recruiting predominantly healthy children and adults will be included. Studies of exercise rehabilitation will be excluded. Medline, Embase, Cinahl, Cochrane Library, SportDiscus, Web of Science, Index Medicus for the Eastern Mediterranean Region and Qscience will be searched. Clinical trial registries including the International Clinical Trials Registry Platform, the Iranian Registry of Clinical Trials and ClinicalTrials.gov will be searched for ongoing and unpublished studies. Searches will be ran from database inception until 1 May 2020 and be supplemented by checking references of key articles. Two reviewers will independently screen identified citations then full texts using prespecified inclusion and exclusion criteria. Piloted data extraction forms will be used in duplicate. Inconsistencies in screening or data extraction will be resolved by a third investigator or study author contact. Risk of bias will be independently assessed by two reviewers using validated tools. A narrative summary of findings will be produced supplemented with meta-analyses and exploration of heterogeneity as appropriate.Ethics and DisseminationThe review aims to strengthen the findings of the primary studies it incorporates and explore the impact of setting. It will synthesise existing published aggregate patient data. If publications or data with ethical concerns are identified, they will be excluded from the review. Results of the systematic review will be published in full and authors will engage directly with research audiences and key stakeholders to share findings.PROSPERO registration number131817.

BackgroundMost adults do not meet the recommended intake of five portions per day of fruit and vegetables (F&V) in England, but economic analyses of structural policies to change diet are sparse.MethodsUsing published data from official statistics and meta-epidemiological studies, we estimated the deaths, years-of-life lost (YLL) and the healthcare costs attributable to consumption of F&V below the recommended five portions per day by English adults. Then, we estimated the cost-effectiveness from governmental and societal perspectives of three policies: a universal 10% subsidy on F&V, a targeted 30% subsidy for low-income households and a social marketing campaign (SMC).FindingsConsumption of F&V below the recommended five portions a day accounted for 16 321 [10 091–23 516] deaths and 238 767 [170 350–311 651] YLL in England in 2017, alongside £705 951 [398 761–1 061 559] million in healthcare costs. All policies would increase consumption and reduce the disease burden attributable to low intake of F&V. From a societal perspective, the incremental cost-effectiveness ratios were £22 891 [22 300–25 079], £16 860 [15 589–19 763] and £25 683 [25 237–28 671] per life-year saved for the universal subsidy, targeted subsidy and SMC, respectively. At a threshold of £20 000 per life-year saved, the likelihood that the universal subsidy, the targeted subsidy and the SMC were cost-effective was 84%, 19% and 5%, respectively. The targeted subsidy would additionally reduce inequalities.ConclusionsLow intake of F&V represents a heavy health and care burden in England. All dietary policies can improve consumption of F&V, but only a targeted subsidy to low-income households would most likely be cost-effective.

OBJECTIVE Diabetes mellitus (DM) increases the risk of infections, but the effect of better control has not been thoroughly investigated. RESEARCH DESIGN AND METHODS With the use of English primary care data, average glycated hemoglobin (HbA1c) during 2008–2009 was estimated for 85,312 patients with DM ages 40–89 years. Infection rates during 2010–2015 compiled from primary care, linked hospital, and mortality records were estimated across 18 infection categories and further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) by HbA1c categories across all DM, and type 1 and type 2 DM separately. IRRs also were compared with 153,341 age-sex-practice–matched controls without DM. Attributable fractions (AF%) among patients with DM were estimated for an optimal control scenario (HbA1c 6–7% [42–53 mmol/mol]). RESULTS Long-term infection risk rose with increasing HbA1c for most outcomes. Compared with patients without DM, those with DM and optimal control (HbA1c 6–7% [42–53 mmol/mol], IRR 1.41 [95% CI 1.36–1.47]) and poor control (≥11% [97 mmol/mol], 4.70 [4.24–5.21]) had elevated hospitalization risks for infection. In patients with type 1 DM and poor control, this risk was even greater (IRR 8.47 [5.86–12.24]). Comparisons within patients with DM confirmed the risk of hospitalization with poor control (2.70 [2.43–3.00]) after adjustment for duration and other confounders. AF% of poor control were high for serious infections, particularly bone and joint (46%), endocarditis (26%), tuberculosis (24%), sepsis (21%), infection-related hospitalization (17%), and mortality (16%). CONCLUSIONS Poor glycemic control is powerfully associated with serious infections and should be a high priority.

There is growing interest in the interaction between type 2 diabetes mellitus (DM) and TB, but many research questions remain unanswered. Epidemiologists, basic scientists, and clinical experts recently convened and identified priorities. This is the first of two reviews on this topic, summarizing priority areas of research regarding epidemiology, clinical management, and public health. First, from an epidemiologic point of view, more study is needed to determine the importance of transient hyperglycemia in patients with TB and on the importance of DM for the global epidemic of multidrug resistant (MDR)-TB. Second, regarding the screening and clinical management of combined TB and DM (TB-DM), clinical trials and large cohort studies should examine the benefits of improved DM care as well as prolonged or intensified TB treatment on the outcome of TB-DM and investigate the cost-effectiveness of screening methods for DM among patients newly diagnosed with TB. Third, from a public health and health systems point of view, the population health impact and cost-effectiveness of different interventions to prevent or treat DM and TB in high-burden populations should be examined, and health-system interventions should be developed for routine TB-DM screening, management of DM after completion of TB treatment, and better access to DM services worldwide. Studies are needed across different ethnicities and settings given the heterogeneity of metabolic perturbations, inflammatory responses, medications, and access to health care. Finally, studies should address interactions between TB, DM, and HIV because of the convergence of epidemics in sub-Saharan Africa and some other parts of the world.

There is growing interest in the re-emerging interaction between type 2 diabetes (DM) and TB, but the underlying biologic mechanisms are poorly understood despite their possible implications in clinical management. Experts in epidemiologic, public health, basic science, and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-occurrence of TB and DM. We identified gaps in current knowledge of altered immunity in patients with DM during TB, where most studies suggest an underperforming innate immunity, but exaggerated adaptive immunity to Mycobacterium tuberculosis. Various molecular mechanisms and pathways may underlie these observations in the DM host. These include signaling induced by excess advanced glycation end products and their receptor, higher levels of reactive oxidative species and oxidative stress, epigenetic changes due to chronic hyperglycemia, altered nuclear receptors, and/or differences in cell metabolism (immunometabolism). Studies in humans at different stages of DM (no DM, pre-DM, and DM) or TB (latent or active TB) should be complemented with findings in animal models, which provide the unique opportunity to study early events in the host-pathogen interaction. Such studies could also help identify biomarkers that will complement clinical studies in order to tailor the prevention of TB-DM, or to avoid the adverse TB treatment outcomes that are more likely in these patients. Such studies will also inform new approaches to host-directed therapies.

Diabetes is associated with failure of tuberculosis (TB) treatment, but it is unclear whether this is related to genotypic drug resistance of the infecting mycobacteria. We used whole genome sequencing (WGS) to examine 1365 known drug resistance mutations in 896 Mycobacterium tuberculosis isolates from TB patients that were screened for diabetes using HbA1c testing as part of the TANDEM project [1]. Ethical approval was received from the London School of Hygiene and Tropical Medicine and institutional review boards in Indonesia and Peru. In Peru we selected all available M. tuberculosis isolates from TANDEM patients (44 with and 445 without diabetes), and in Indonesia we selected all available isolates from diabetic patients (n=115) plus a subset of isolates from non-diabetic patients (n=292) from the same clinics, during the same time period, frequency-matched by age. We used TB Profiler version 0.3.8 [2] to determine M. tuberculosis lineage and drug resistance. A phylogeny was constructed using PhyML version 3.0 [3], and the minimum pairwise distance for isolates was calculated separately for patients with and without diabetes, stratified by country. We examined if diabetes was associated with genotypic drug resistance against individual drugs or with MDR-TB for the two countries separately and combined, with multilevel multivariable logistic regression, taking into account the country of origin and adjusting for age, gender, HIV-infection, previous TB treatment, and M. tuberculosis lineage

BackgroundDiabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa.MethodsAge-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors.ResultsOf 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus–infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB–DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB–DM patients were older and had a higher body mass index (BMI) (P value < .05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value < .05).ConclusionsWe show that DM prevalence and clinical characteristics of TB–DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB–DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM.

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Background The aim of this study was to estimate the impact of reducing the prevalence of obesity, smoking, and physical inactivity, and introducing physical activity as an explicit intervention, on the burden of type 2 diabetes mellitus (T2DM), using Qatar as an example. Methods A population-level mathematical model was adapted and expanded. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status, and parameterized by nationally representative data. Modeled interventions were introduced in 2016, reached targeted level by 2031, and then maintained up to 2050. Diverse intervention scenarios were assessed and compared with a counter-factual no intervention baseline scenario. Results T2DM prevalence increased from 16.7% in 2016 to 24.0% in 2050 in the baseline scenario. By 2050, through halting the rise or reducing obesity prevalence by 10–50%, T2DM prevalence was reduced by 7.8–33.7%, incidence by 8.4–38.9%, and related deaths by 2.1–13.2%. For smoking, through halting the rise or reducing smoking prevalence by 10–50%, T2DM prevalence was reduced by 0.5–2.8%, incidence by 0.5–3.2%, and related deaths by 0.1–0.7%. For physical inactivity, through halting the rise or reducing physical inactivity prevalence by 10–50%, T2DM prevalence was reduced by 0.5–6.9%, incidence by 0.5–7.9%, and related deaths by 0.2–2.8%. Introduction of physical activity with varying intensity at 25% coverage reduced T2DM prevalence by 3.3–9.2%, incidence by 4.2–11.5%, and related deaths by 1.9–5.2%. Conclusions Major reductions in T2DM incidence could be accomplished by reducing obesity, while modest reductions could be accomplished by reducing smoking and physical inactivity, or by introducing physical activity as an intervention.

Background In context of the rapidly expanding diabetes mellitus (DM) epidemic in India and slowly declining tuberculosis (TB) incidence, we aimed to estimate the past, current, and future impact of DM on TB epidemiology. Methods An age-structured TB-DM dynamical mathematical model was developed and analyzed to assess the DM-on-TB impact. The model was calibrated using a literature review and meta-analyses. The DM-on-TB impact was analyzed using population attributable fraction metrics. Sensitivity analyses were conducted by accommodating less conservative effect sizes for the TB-DM interactions, by factoring the age-dependence of the TB-DM association, and by assuming different TB disease incidence rate trajectories. Results In 1990, 11.4% (95% uncertainty interval (UI) = 6.3%-14.4%) of new TB disease incident cases were attributed to DM. This proportion increased to 21.9% (95% UI = 12.1%-26.4%) in 2017, and 33.3% (95% UI = 19.0%-44.1%) in 2050. Similarly, in 1990, 14.5% (95% UI = 9.5%-18.2%) of TB-related deaths were attributed to DM. This proportion increased to 28.9% (95% UI = 18.9%-34.1%) in 2017, and 42.8% (95% UI = 28.7%-53.1%) in 2050. The largest impacts originated from the effects of DM on TB disease progression and infectiousness. Sensitivity analyses suggested that the impact could be even greater. Conclusions The burgeoning DM epidemic is predicted to become a leading driver of TB disease incidence and mortality over the coming decades. By 2050, at least one-third of TB incidence and almost half of TB mortality in India will be attributed to DM. This is likely generalizable to other Asian Pacific countries with similar TB-DM burdens. Targeting the impact of the increasing DM burden on TB control is critical to achieving the goal of TB elimination by 2050.

Introduction Tobacco smoking is a significant public health threat in the world, a risk factor for many diseases, and has been increasing in prevalence in many developing countries. In this study, we aimed to estimate the burden of premature deaths attributable to smoking among Tunisian men aged 35-69 years in 2009. Methods The number of deaths attributable to smoking was estimated using the population attributable risk fraction method. Smoking prevalence was obtained from a nationally representative survey. Causes of death were obtained from the registry of the National Public Health Institute. Relative risks were taken from the American Cancer Society Prevention Study (CPS-II). Results Total estimated premature deaths attributable to smoking among men in Tunisia were 2601 (95% CI: 2268-2877), accounting for 25% (95% CI: 23.3-26.6) of total male adult mortality. Cancer, cardiovascular and respiratory diseases were the major causes of premature deaths attributable to smoking with 1272 (95% CI: 1188-1329), 966 (95% CI: 779-1133) and 364 (300-415) deaths, respectively. Conclusions Tobacco smoking is highly relevant and is related to substantial premature mortality in Tunisia, around double that estimated for the region as a whole. This also has not decreased over the past 20 years. Urgent actions are needed to reduce this pandemic.

Background Data regarding the incidence of tuberculosis (TB) among people living with diabetes (PLWD) in TB-endemic settings are scarce. We examined TB incidence among PLWD in Indonesia who had previously been screened for latent TB infection (LTBI) and TB disease. Methods PLWD (≥18 y of age) in an urban setting were examined a mean 3.4 y after they had been screened for active TB and LTBI. Data on subsequent TB diagnosis were collected by interview and with chest X-ray, sputum smear and Mycobacterium tuberculosis culture. TB incidence rates were stratified for baseline LTBI status, as determined by the QuantiFERON interferon-gamma release assay (IGRA). Results Of 590 PLWD, 101 had died and 163 could not be contacted or refused. Among the 326 who were re-examined, 6 (1.8%; 95% confidence interval [CI] 0.7 to 4.0) reported being diagnosed already and a further 5 were diagnosed with active TB (1.5%; 95% CI 0.50 to 3.5). The TB incidence rate was 9.85 (95% CI 4.03 to 15.68) per 1000 person-years. TB incidence was higher among PLWD with baseline LTBI (17.13; 95% CI 5.25 to 29.00/1000 person-years) compared with those without LTBI (4.79; 95% CI −0.63 to 10.21), with an incidence rate ratio of 3.57 (95% CI 0.86 to 20.92; p=0.054). Conclusions PLWD with LTBI in Indonesia and similar settings are likely to benefit from TB preventive therapy.

BACKGROUND: Previous evidence synthesis has suggested diabetes mellitus (DM) worsens tuberculosis (TB) treatment outcomes. However, these reviews are limited by the number, robustness and conflicting results among the studies included. We conducted a systematic review to update earlier analyses and explore heterogeneity among studies.\ud \ud METHODS: MEDLINE, EMBASE, AIM, LILACS, IMEMR, IMSEAR and WPRIM were searched between 1 January 1980 and 23 July 2018 unrestricted by language or region. All cohort and case-control studies investigating the difference in TB treatment outcomes amongst TB-DM patients compared to those with TB alone were included. Two reviewers independently assessed titles, abstracts, and extracted data. Culture conversion at two/three months, all-cause mortality, treatment failure, relapse and multidrug-resistant TB (MDR-TB) were evaluated using random effects meta-analysis with generic inverse variance. Heterogeneity was explored using subgroup analyses and meta-regression.\ud \ud RESULTS: One hundred and four publications were identified. Sixty-four studies including 56 122 individuals with TB-DM and 243 035 with TB, reported on death. Some outcomes showed substantial heterogeneity between studies, which we could not fully explain, though confounding adjustment and country income level accounted for some of the differences. TB-DM patients had higher odds of death (OR 1.88, 95%CI 1.59–2.21) and relapse (OR 1.64, 95%CI 1.29–2.08) compared to TB patients. More limited evidence suggested TB-DM patients had double the risk of developing MDR-TB (OR 1.98, 95%CI 1.51–2.60).\ud \ud CONCLUSION: DM is associated with increased risks of poor TB treatment outcomes, particularly mortality, and may increase risk of developing primary MDR-TB. Cost-effectiveness of interventions to enhance TB-DM treatment should be assessed.

We aimed to develop a conceptual framework of diabetes mellitus (DM) effects on tuberculosis (TB) natural history and treatment outcomes, and to assess the impact of these effects on TB-transmission dynamics. The model was calibrated using TB data for India. A conceptual framework was developed based on a literature review, and then translated into a mathematical model to assess the impact of the DM-on-TB effects. The impact was analyzed using TB-disease incidence hazard ratio (HR) and population attributable fraction (PAF) measures. Evidence was identified for 10 plausible DM-on-TB effects. Assuming a flat change of 300% (meaning an effect size of 3.0) for each DM-on-TB effect, the HR ranged between 1.0 (Effect 9-Recovery) and 2.7 (Effect 2-Fast progression); most effects did not have an impact on the HR. Meanwhile, TB-disease incidence attributed directly and indirectly to each effect ranged between −4.6% (Effect 7-TB mortality) and 34.5% (Effect 2-Fast progression). The second largest impact was for Effect 6-Disease infectiousness at 29.9%. In conclusion, DM can affect TB-transmission dynamics in multiple ways, most of which are poorly characterized and difficult to assess in epidemiologic studies. The indirect (e.g. onward transmission) impacts of some DM-on-TB effects are comparable in scale to the direct impacts. While the impact of several effects on the HR was limited, the impact on the PAF was substantial suggesting that DM could be impacting TB epidemiology to a larger extent than previously thought.

We thank Drs Yates and Barr for their valuable comments. In our article [1], we were not attempting to assess the extent to which dysglycemia is causally associated with tuberculosis (TB). A number of prospective studies exist, among a body of evidence, supporting probabilistic causation between diabetes mellitus (DM) and TB [2, 3]. Rather, the aim of our study was to identify age-adjusted prevalence and clinical characteristics of DM and intermediate hyperglycemia among those with newly diagnosed TB across 4 TB-endemic settings. In our South African population, the prevalence of DM (10.9% [95% confidence interval, 7%–14.9%]) was the...