Quasi-experimental evaluation of a nationwide diabetes prevention programme.

Diabetes is a leading cause of morbidity, mortality and cost of illness1,2. Health behaviours, particularly those related to nutrition and physical activity, play a key role in the development of type 2 diabetes mellitus3. Whereas behaviour change programmes (also known as lifestyle interventions or similar) have been found efficacious in controlled clinical trials4,5, there remains controversy about whether targeting health behaviours at the individual level is an effective preventive strategy for type 2 diabetes mellitus6 and doubt among clinicians that lifestyle advice and counselling provided in the routine health system can achieve improvements in health7-9. Here we show that being referred to the largest behaviour change programme for prediabetes globally (the English Diabetes Prevention Programme) is effective in improving key cardiovascular risk factors, including glycated haemoglobin (HbA1c), excess body weight and serum lipid levels. We do so by using a regression discontinuity design10, which uses the eligibility threshold in HbA1c for referral to the behaviour change programme, in electronic health data from about one-fifth of all primary care practices in England. We confirm our main finding, the improvement of HbA1c, using two other quasi-experimental approaches: difference-in-differences analysis exploiting the phased roll-out of the programme and instrumental variable estimation exploiting regional variation in programme coverage. This analysis provides causal, rather than associational, evidence that lifestyle advice and counselling implemented at scale in a national health system can achieve important health improvements.

Herpes zoster vaccination and new diagnoses of dementia: A quasi-randomized study in Australia.

Increasing evidence suggests that neurotropic herpesviruses could play a role in the development of dementia, possibly through a neuroinflammatory process. Herpes zoster (HZ) vaccination has been reported to lead to a reduced probability of being diagnosed with dementia in several correlational studies and in a prior analysis by our team in Wales. This present study constitutes the first investigation to use a quasi-randomized study design in an electronic health record dataset from a large and diverse nation (Australia) to aim to determine the effect of HZ vaccination on dementia. In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age through primary care providers. Thus, those whose 80th birthday was just a few days prior to November 1 2016 never became eligible, whereas those whose 80th birthday was just a few days later were eligible. The key advantage of our approach is that one would not expect that these population groups who differ in their age by only a minute degree would, on average, differ in any of their health characteristics and behaviors. We used detailed primary healthcare records with week-of-birth information from 65 general practices across Australia. We analyzed our data using a regression discontinuity approach. Our sample consisted of 101,219 patients. As expected, patients born just before versus shortly after the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination were well-balanced in their past preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 15.7 (95% CI: [12.2 - 19.3], p < 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the eligibility threshold. The eligibility rules of the HZ vaccination program, thus, created comparison groups just on either side of the date-of-birth eligibility threshold who were similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. Eligibility for HZ vaccination (i.e., being born shortly before versus shortly after November 2 1936) decreased the probability of receiving a new dementia diagnosis over 7.4 years by 2.0 percentage points (95% CI: [0.3 - 3.7], p = 0.021). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations), nor the probability of being diagnosed with other common chronic conditions than dementia. This study provides important evidence on the potential benefits of HZ vaccination for dementia because its quasi-randomized design allows for conclusions that are more likely to be causal than those of the existing associational evidence.

The prevalence of cardiovascular disease risk factors among adults living in extreme poverty.

Evidence on cardiovascular disease (CVD) risk factor prevalence among adults living below the World Bank's international line for extreme poverty (those with income <$1.90 per day) globally is sparse. Here we pooled individual-level data from 105 nationally representative household surveys across 78 countries, representing 85% of people living in extreme poverty globally, and sorted individuals by country-specific measures of household income or wealth to identify those in extreme poverty. CVD risk factors (hypertension, diabetes, smoking, obesity and dyslipidaemia) were present among 17.5% (95% confidence interval (CI) 16.7-18.3%), 4.0% (95% CI 3.6-4.5%), 10.6% (95% CI 9.0-12.3%), 3.1% (95% CI 2.8-3.3%) and 1.4% (95% CI 0.9-1.9%) of adults in extreme poverty, respectively. Most were not treated for CVD-related conditions (for example, among those with hypertension earning <$1.90 per day, 15.2% (95% CI 13.3-17.1%) reported taking blood pressure-lowering medication). The main limitation of the study is likely measurement error of poverty level and CVD risk factors that could have led to an overestimation of CVD risk factor prevalence among adults in extreme poverty. Nonetheless, our results could inform equity discussions for resource allocation and design of effective interventions.

Achieving behavior change at scale: Causal evidence from a national lifestyle intervention program for pre-diabetes in the UK.

There remains widespread doubt among clinicians that mere lifestyle advice and counseling provided in routine care can achieve improvements in health. We aimed to determine the health effects of the largest behavior change program for pre-diabetes globally (the English Diabetes Prevention Programme) when implemented at scale in routine care. We exploited the threshold in glycated hemoglobin (HbA1c) used to decide on program eligibility by applying a regression discontinuity design, one of the most credible quasi-experimental strategies for causal inference, to electronic health data from approximately one-fifth of all primary care practices in England. Program referral led to significant improvements in patients' HbA1c and body mass index. This analysis provides causal, rather than associational, evidence that lifestyle advice and counseling implemented in a national health system can achieve important health improvements.

IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045.

AIMS: To provide global, regional, and country-level estimates of diabetes prevalence and health expenditures for 2021 and projections for 2045. METHODS: A total of 219 data sources meeting pre-established quality criteria reporting research conducted between 2005 and 2020 and representing 215 countries and territories were identified. For countries without data meeting quality criteria, estimates were extrapolated from countries with similar economies, ethnicity, geography and language. Logistic regression was used to generate smoothed age-specific diabetes prevalence estimates. Diabetes-related health expenditures were estimated using an attributable fraction method. The 2021 diabetes prevalence estimates were applied to population estimates for 2045 to project future prevalence. RESULTS: The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million people), rising to 12.2% (783.2 million) in 2045. Diabetes prevalence was similar in men and women and was highest in those aged 75-79 years. Prevalence (in 2021) was estimated to be higher in urban (12.1%) than rural (8.3%) areas, and in high-income (11.1%) compared to low-income countries (5.5%). The greatest relative increase in the prevalence of diabetes between 2021 and 2045 is expected to occur in middle-income countries (21.1%) compared to high- (12.2%) and low-income (11.9%) countries. Global diabetes-related health expenditures were estimated at 966 billion USD in 2021, and are projected to reach 1,054 billion USD by 2045. CONCLUSIONS: Just over half a billion people are living with diabetes worldwide which means that over 10.5% of the world's adult population now have this condition.

Patterns of tobacco use in low and middle income countries by tobacco product and sociodemographic characteristics: nationally representative survey data from 82 countries.

OBJECTIVES: To determine the prevalence and frequency of using any tobacco product and each of a detailed set of tobacco products, how tobacco use and frequency of use vary across countries, world regions, and World Bank country income groups, and the socioeconomic and demographic gradients of tobacco use and frequency of use within countries. DESIGN: Secondary analysis of nationally representative, cross-sectional, household survey data from 82 low and middle income countries collected between 1 January 2015 and 31 December 2020. SETTING: Population based survey data. PARTICIPANTS: 1 231 068 individuals aged 15 years and older. MAIN OUTCOME MEASURES: Self-reported current smoking, current daily smoking, current smokeless tobacco use, current daily smokeless tobacco use, pack years, and current use and use frequencies of each tobacco product. Products were any type of cigarette, manufactured cigarette, hand rolled cigarette, water pipe, cigar, oral snuff, nasal snuff, chewing tobacco, and betel nut (with and without tobacco). RESULTS: The smoking prevalence in the study sample was 16.5% (95% confidence interval 16.1% to 16.9%) and ranged from 1.1% (0.9% to 1.3%) in Ghana to 50.6% (45.2% to 56.1%) in Kiribati. The user prevalence of smokeless tobacco was 7.7% (7.5% to 8.0%) and prevalence was highest in Papua New Guinea (daily user prevalence of 65.4% (63.3% to 67.5%)). Although variation was wide between countries and by tobacco product, for many low and middle income countries, the highest prevalence and cigarette smoking frequency was reported in men, those with lower education, less household wealth, living in rural areas, and higher age. CONCLUSIONS: Both smoked and smokeless tobacco use and frequency of use vary widely across tobacco products in low and middle income countries. This study can inform the design and targeting of efforts to reduce tobacco use in low and middle income countries and serve as a benchmark for monitoring progress towards national and international goals.

Correlates of HIV seropositivity in young West and Central African women: A pooled analysis of 17 Demographic and Health Surveys.

BACKGROUND: Young women in West and Central Africa have been described by the United Nations as being especially vulnerable to HIV/AIDS. Despite a consensus that increased efforts are necessary to address the needs of this particular demographic, correlates of HIV seropositivity in young West and Central African women have not been systematically described. This study fills this gap using a rich set of publicly available survey data. METHODS: For this cross-sectional study, we combined HIV test results for young women (age 15-24 years) with information on demographic, cultural and socioeconomic correlates from 17 recent Demographic and Health Surveys (DHS) to estimate odds ratios (OR) from fixed effects logistic regression models accounting for potential individual, household-level and contextual risk factors of HIV seropositivity. RESULTS: The prevalence of HIV seropositivity among young women is higher than for men of the same age in all included surveys, except for the Burkina Faso DHS. An important correlate of HIV seropositivity in young women is early sexual activity (OR = 1.510; 95% confidence interval (CI) = 1.100, 2.072), while higher education is associated with reduced odds of being HIV positive (OR = 0.215; 95% CI = 0.057, 0.820). No significant correlation has been found for individual HIV awareness, but HIV stigma is negatively associated with HIV seropositivity (OR = 0.495; 95% CI = 0.247, 0.990, in the fully adjusted model). CONCLUSIONS: The results demonstrate the need to design effective policies addressing behavioral risks in young women. In particular, increasing HIV awareness alone is likely to be insufficient. Instead, information campaigns need to focus on transforming awareness into behavioral change. Moreover, fostering formal education may be an effective tool in the fight against HIV/AIDS.

The effect of routine probiotics supplementation on preterm newborn health: a regression discontinuity analysis.

BACKGROUND: Despite ongoing debate about the health impact of probiotics, rigorous evidence assessing the use of probiotics in routine preterm newborn care is lacking. OBJECTIVES: We aimed to estimate the causal effect of routine probiotics supplementation on moderately preterm newborns' anthropometric development (weight-for-age and height-for-age z scores) and risk of late-onset sepsis. METHODS: This study used a regression discontinuity analysis based on hospital guidelines that recommended routine probiotics supplementation for neonates born before 34 completed weeks of gestation. Data for this study came from electronic medical records of a level III neonatal care center in Germany and were collected between 2013 and 2019. Newborns born between 30 to 38 completed weeks of gestation without severe congenital defects were eligible for inclusion. Outcomes were weight-for-age and height-for-age z scores at discharge as well as late-onset sepsis. RESULTS: Study participants included 1734 preterm neonates. The results showed no significant intention-to-treat effect on weight-for-age (effect: -0.033 SD; 95% CI: -0.220, 0.155), length-for-age (-0.133 SD; 95% CI: -0.380, 0.114), or late-onset sepsis probability (-1.175 percentage points; 95% CI: -6.556, 4.205). There was no evidence for significant effects of probiotics for any of the study's endpoints on those complying with the hospital guidelines (local average treatment effect). CONCLUSIONS: Routine treatment of moderately preterm newborns with probiotics is unlikely to improve anthropometric outcomes. Complier-level analysis suggested that this finding was not simply driven by a lack of physician compliance with hospital guidelines but by an overall absence of large health effects from the treatment itself. Moreover, overall sepsis risk was low and did not change significantly as a result of probiotics supplementation. The findings of this study therefore do not support the routine use of probiotics for improving growth or preventing late-onset sepsis in moderately preterm neonates.

Global and regional estimates and projections of diabetes-related health expenditure: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.

AIMS: Diabetes and its complications have a significant economic impact on individuals and their families, health systems and national economies. METHODS: The direct health expenditure of diabetes was calculated relying on the following inputs: diagnosed and undiagnosed diabetes prevalence estimates, United Nations population estimates, World Health Organization health expenditure per capita and ratios of health expenditure for people with diabetes compared to people without diabetes. RESULTS: The estimated global direct health expenditure on diabetes in 2019 is USD 760 billion and is expected to grow to a projected USD 825 billion by 2030 and USD 845 billion by 2045. There is a wide variation in annual health expenditures on diabetes. The United States of America has the highest estimated expenditure with USD 294.6 billion, followed by China and Brazil, with USD 109.0 billion and USD 52.3 billion, respectively. The age group with the largest annual diabetes-related health expenditure is 60-69 years with USD 177.7 billion, followed by 50-59 years, and 70-79 years with USD 173.0 billion and USD 171.5 billion, respectively. Slightly higher diabetes-related health expenditure is seen in women than in men (USD 382.6 billion vs. USD 377.6 billion, respectively). The same difference is expected to be present in 2030 and 2045. CONCLUSIONS: There were large disparities between high-, middle- and low-income countries with total health expenditures in high-income countries being over 300 times those in low-income countries. The ratio for annual direct health expenditure per person between these groups of countries is more than 38-fold.

How socioeconomic status moderates the stunting-age relationship in low-income and middle-income countries.

INTRODUCTION: Reducing stunting is an important part of the global health agenda. Despite likely changes in risk factors as children age, determinants of stunting are typically analysed without taking into account age-related heterogeneity. We aim to fill this gap by providing an in-depth analysis of the role of socioeconomic status (SES) as a moderator for the stunting-age pattern. METHODS: Epidemiological and socioeconomic data from 72 Demographic and Health Surveys (DHS) were used to calculate stunting-age patterns by SES quartiles, derived from an index of household assets. We further investigated how differences in age-specific stunting rates between children from rich and poor households are explained by determinants that could be modified by nutrition-specific versus nutrition-sensitive interventions. RESULTS: While stunting prevalence in the pooled sample of 72 DHS is low in children up to the age of 5 months (maximum prevalence of 17.8% (95% CI 16.4;19.3)), stunting rates in older children tend to exceed those of younger ones in the age bracket of 6-20 months. This pattern is more pronounced in the poorest than in the richest quartile, with large differences in stunting prevalence at 20 months (stunting rates: 40.7% (95% CI 39.5 to 41.8) in the full sample, 50.3% (95% CI 48.2 to 52.4) in the poorest quartile and 29.2% (95% CI 26.8 to 31.5) in the richest quartile). When adjusting for determinants related to nutrition-specific interventions only, SES-related differences decrease by up to 30.1%. Much stronger effects (up to 59.2%) occur when determinants related to nutrition-sensitive interventions are additionally included. CONCLUSION: While differences between children from rich and poor households are small during the first 5 months of life, SES is an important moderator for age-specific stunting rates in older children. Determinants related to nutrition-specific interventions are not sufficient to explain these SES-related differences, which could imply that a multifactorial approach is needed to reduce age-specific stunting rates in the poorest children.

Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030.

OBJECTIVE: Despite the importance of diabetes for global health, the future economic consequences of the disease remain opaque. We forecast the full global costs of diabetes in adults through the year 2030 and predict the economic consequences of diabetes if global targets under the Sustainable Development Goals (SDG) and World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020 are met. RESEARCH DESIGN AND METHODS: We modeled the absolute and gross domestic product (GDP)-relative economic burden of diabetes in individuals aged 20-79 years using epidemiological and demographic data, as well as recent GDP forecasts for 180 countries. We assumed three scenarios: prevalence and mortality 1) increased only with urbanization and population aging (baseline scenario), 2) increased in line with previous trends (past trends scenario), and 3) achieved global targets (target scenario). RESULTS: The absolute global economic burden will increase from U.S. $1.3 trillion (95% CI 1.3-1.4) in 2015 to $2.2 trillion (2.2-2.3) in the baseline, $2.5 trillion (2.4-2.6) in the past trends, and $2.1 trillion (2.1-2.2) in the target scenarios by 2030. This translates to an increase in costs as a share of global GDP from 1.8% (1.7-1.9) in 2015 to a maximum of 2.2% (2.1-2.2). CONCLUSIONS: The global costs of diabetes and its consequences are large and will substantially increase by 2030. Even if countries meet international targets, the global economic burden will not decrease. Policy makers need to take urgent action to prepare health and social security systems to mitigate the effects of diabetes.

The association of parental education with childhood undernutrition in low- and middle-income countries: comparing the role of paternal and maternal education.

Background: Most existing research on the association of parental education with childhood undernutrition focuses on maternal education and often ignores paternal education. We systematically investigate differences in maternal and paternal education and their association with childhood undernutrition. Methods: One hundred and eighty Demographic and Health Surveys from 62 countries performed between 1990 and 2014 were analysed. We used linear-probability models to predict childhood undernutrition prevalences, measured as stunting, underweight and wasting, for all combinations of maternal and paternal attainment in school. Models were adjusted for demographic and socio-economic covariates for the child, mother and household, country-level fixed effects and clustering. Additional specifications adjust for local area characteristics instead of country fixed effects. Results: Both higher maternal and paternal education levels are associated with lower childhood undernutrition. In regressions adjusted for child age and sex as well as country-level fixed effects, the association is stronger for maternal education than for paternal education when their combined level of education is held constant. In the fully adjusted models, the observed differences in predicted undernutrition prevalences are strongly attenuated, suggesting a similar importance of maternal and paternal education. These findings are confirmed by the analysis of composite schooling indicators. Conclusions: We find that paternal education is similarly important for reducing childhood undernutrition as maternal education and should therefore receive increased attention in the literature.

The global economic burden of diabetes in adults aged 20-79 years: a cost-of-illness study.

BACKGROUND: Differences in methods and data used in past studies have limited comparisons of the cost of illness of diabetes across countries. We estimate the full global economic burden of diabetes in adults aged 20-79 years in 2015, using a unified framework across all countries. Our objective was to highlight patterns of diabetes-associated costs as well as to identify the need for further research in low-income regions. METHODS: Epidemiological and economic data for 184 countries were used to estimate the global economic burden of diabetes, regardless of diabetes type. Direct costs were derived using a top-down approach based on WHO general health expenditure figures and prevalence data from the 2015 International Diabetes Federation Diabetes Atlas. Indirect costs were assessed using a human-capital approach, including diabetes-associated morbidity and premature mortality. FINDINGS: We estimate the global cost of diabetes for 2015 was US$1·31 trillion (95% CI 1·28-1·36) or 1·8% (95% CI 1·8-1·9) of global gross domestic product (GDP). Notably, indirect costs accounted for 34·7% (95% CI 34·7-35·0) of the total burden, although substantial variations existed both in the share and the composition of indirect costs across countries. North America was the most affected region relative to GDP and also the largest contributor to global absolute costs. However, on average, the economic burden as percentage of GDP was larger in middle-income countries than in high-income countries. INTERPRETATION: Our results suggest a substantial global economic burden of diabetes. Although limited data were available for low-income and middle-income countries, our findings suggest that large diabetes-associated costs are not only a problem in high-income settings but also affect poorer world regions. FUNDING: None.

Quasi-experimental study designs series-paper 7: assessing the assumptions.

Quasi-experimental designs are gaining popularity in epidemiology and health systems research-in particular for the evaluation of health care practice, programs, and policy-because they allow strong causal inferences without randomized controlled experiments. We describe the concepts underlying five important quasi-experimental designs: Instrumental Variables, Regression Discontinuity, Interrupted Time Series, Fixed Effects, and Difference-in-Differences designs. We illustrate each of the designs with an example from health research. We then describe the assumptions required for each of the designs to ensure valid causal inference and discuss the tests available to examine the assumptions.