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1.
BMJ Glob Health ; 9(4)2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637119

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.


COVID-19 , Female , Male , Humans , Pandemics , Italy , Greece , Age Factors
2.
Diabetes Res Clin Pract ; 211: 111641, 2024 May.
Article En | MEDLINE | ID: mdl-38548108

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.


Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Primary Health Care , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/epidemiology , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Female , Male , Middle Aged , Aged , Adult , Primary Health Care/statistics & numerical data , Aged, 80 and over , Risk Factors , Infections/epidemiology , Adolescent , Young Adult , Age Factors , Cohort Studies , England/epidemiology , Sex Factors , Ethnicity/statistics & numerical data , Prospective Studies
3.
Lancet Planet Health ; 8(3): e197-e212, 2024 03.
Article En | MEDLINE | ID: mdl-38453385

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.


Consumer Behavior , Diet, Healthy , Motivation , Humans , Fruit/economics , Vegetables/economics , Commerce
4.
Diabetes Res Clin Pract ; 207: 111023, 2024 Jan.
Article En | MEDLINE | ID: mdl-37984487

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.


Diabetes Mellitus, Type 1 , Infections , Humans , Diabetes Mellitus, Type 1/epidemiology , Glycated Hemoglobin , Cohort Studies , Infections/etiology , Infections/complications , Hospitalization
5.
Sci Rep ; 13(1): 19894, 2023 11 14.
Article En | MEDLINE | ID: mdl-37963989

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease.


Diabetes Mellitus , Latent Tuberculosis , Tuberculosis , Adult , Humans , Risk Factors , Diabetes Mellitus/epidemiology , Tuberculosis/complications , Tuberculosis/epidemiology , Latent Tuberculosis/complications , Africa/epidemiology , Prevalence
6.
Eur J Anaesthesiol ; 40(11): 826-832, 2023 11 01.
Article En | MEDLINE | ID: mdl-37646501

BACKGROUND: Guidelines from the Obstetric Anaesthetists' Association and Difficult Airway Society state that 'a videolaryngoscope should be immediately available for all obstetric general anaesthetics'. OBJECTIVE: To report the incidence of videolaryngoscopy use, and other airway management safety interventions, in an obstetric population before and after various quality improvement interventions. DESIGN: Prospective data collection was undertaken over 18 months, divided into three separate 6-month periods: June to November 2019; March to August 2021; January to June 2022. These periods relate to evaluation of specific quality improvement interventions. SETTING: The project was carried out in a large tertiary referral obstetric unit. PATIENTS: We identified 401 pregnant women (> 20 weeks' gestation) and postnatal women (up to 48 h post delivery) undergoing an obstetric surgical procedure under general anaesthesia. INTERVENTIONS: To standardise practice, an intubation checklist was introduced in December 2020 and multidisciplinary staff training in August 2021. MAIN OUTCOME MEASURES: Primary outcome measures were use of a Macintosh-style videolaryngoscope and tracheal intubation success. Secondary outcome measures were use of an intubation checklist; low flow nasal oxygen; and ramped patient positioning. RESULTS: Data from 334 tracheal intubations (83.3% of cases) were recorded. Videolaryngoscope use increased from 60% in 2019, to 88% in 2021, to 94% in 2022. Tracheal intubation was successful in all patients, with 94% first pass success overall and only 0.9% requiring three attempts. Use of secondary outcome measures also increased: low flow nasal oxygen from 48% in 2019 to 90% in 2022; ramped positioning from 95% in 2021 to 97% in 2022; and checklist use from 63% in 2021 to 92% in 2022. CONCLUSIONS: We describe the successful adoption of simple safety measures introduced into routine practice. These comprised videolaryngoscopy, ramped positioning and low flow nasal oxygen. Their introduction was supported by the implementation of an intubation checklist and multidisciplinary team training.


Laryngoscopes , Laryngoscopy , Humans , Female , Pregnancy , Laryngoscopy/adverse effects , Laryngoscopy/methods , Quality Improvement , Intubation, Intratracheal/methods , Airway Management/adverse effects , Airway Management/methods , Oxygen
7.
Clin Transl Med ; 13(9): e1375, 2023 09.
Article En | MEDLINE | ID: mdl-37649224

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.


Diabetes Mellitus , Hyperglycemia , Humans , Transcriptome/genetics , Comorbidity , Gene Expression Profiling
8.
Front Public Health ; 11: 1167807, 2023.
Article En | MEDLINE | ID: mdl-37404285

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, Type 2 , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Public Health , Qatar/epidemiology , Obesity/epidemiology , Models, Theoretical , Vegetables
9.
Open Forum Infect Dis ; 10(6): ofad255, 2023 Jun.
Article En | MEDLINE | ID: mdl-37383249

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.

10.
Diabetes Care ; 46(6): 1209-1217, 2023 06 01.
Article En | MEDLINE | ID: mdl-37043827

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.


Diabetes Mellitus, Type 2 , Infections , Prediabetic State , Humans , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Prediabetic State/epidemiology , Ethnicity , Comorbidity , Infections/epidemiology
11.
Int J Epidemiol ; 52(3): 664-676, 2023 06 06.
Article En | MEDLINE | ID: mdl-36029524

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.


COVID-19 , Female , Male , Humans , COVID-19/epidemiology , Pandemics , Italy , France , Age Factors , Mortality
12.
BMJ Open ; 12(11): e060786, 2022 Nov 08.
Article En | MEDLINE | ID: mdl-36351737

OBJECTIVE: Contemporary 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. METHODS: We 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. RESULTS: In 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. CONCLUSION: Attainment 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.


Diabetes Mellitus, Type 2 , Diabetic Foot , Diabetic Neuropathies , Peripheral Arterial Disease , Retinal Diseases , Adult , Female , Humans , Male , Glycated Hemoglobin , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Diabetic Foot/epidemiology , Diabetic Foot/therapy , Diabetic Foot/complications , Africa/epidemiology , Peripheral Arterial Disease/complications
13.
EBioMedicine ; 82: 104173, 2022 Aug.
Article En | MEDLINE | ID: mdl-35841871

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).


Diabetes Mellitus , Tuberculosis , Adult , Antitubercular Agents/therapeutic use , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Humans , Longitudinal Studies , Treatment Outcome , Tuberculosis/diagnosis
14.
Trials ; 23(1): 480, 2022 Jun 10.
Article En | MEDLINE | ID: mdl-35689272

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.


Diabetes Mellitus, Type 2 , Isoniazid , Latent Tuberculosis , Rifampin , Adult , Antitubercular Agents/adverse effects , Cohort Studies , Diabetes Mellitus, Type 2/epidemiology , HIV Infections/epidemiology , Humans , Isoniazid/adverse effects , Latent Tuberculosis/prevention & control , Randomized Controlled Trials as Topic , Rifampin/adverse effects , Rifampin/analogs & derivatives , Tanzania/epidemiology
15.
BMJ Open ; 12(5): e053541, 2022 05 11.
Article En | MEDLINE | ID: mdl-35545390

BACKGROUND: Using 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. METHODS: Our 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. RESULTS: T2DM 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. CONCLUSION: T2DM 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.


Diabetes Mellitus, Type 2 , Adult , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Female , Humans , Male , Models, Theoretical , Obesity/complications , Obesity/epidemiology , Prevalence , Risk Factors , Turkey/epidemiology
16.
Article En | MEDLINE | ID: mdl-35443971

INTRODUCTION: We 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 METHODS: An 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. RESULTS: Between 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. CONCLUSIONS: T2DM 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.


Diabetes Mellitus, Type 2 , Diabetes Mellitus, Type 2/epidemiology , Humans , Models, Theoretical , Obesity/epidemiology , Qatar/epidemiology , Risk Factors
17.
Tuberculosis (Edinb) ; 134: 102164, 2022 05.
Article En | MEDLINE | ID: mdl-35288340

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.


Diabetes Mellitus , Mycobacterium tuberculosis , Tuberculosis, Osteoarticular , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Humans , Indonesia/epidemiology , Models, Theoretical , Risk Factors
18.
Trop Med Int Health ; 27(4): 369-386, 2022 04.
Article En | MEDLINE | ID: mdl-35146851

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.


Diabetes Mellitus , Tuberculosis , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Humans , Odds Ratio , Risk Factors , Tuberculosis/complications , Tuberculosis/epidemiology
19.
BMC Public Health ; 22(1): 54, 2022 01 09.
Article En | MEDLINE | ID: mdl-35000578

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.


COVID-19 , Aged , Brazil , Female , Humans , Life Expectancy , Male , Mortality , Mortality, Premature , Pandemics , SARS-CoV-2 , United States
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