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.

Avoiding C-hacking when evaluating survival distribution predictions with discrimination measures.

MOTIVATION: In this article, we consider how to evaluate survival distribution predictions with measures of discrimination. This is non-trivial as discrimination measures are the most commonly used in survival analysis and yet there is no clear method to derive a risk prediction from a distribution prediction. We survey methods proposed in literature and software and consider their respective advantages and disadvantages. RESULTS: Whilst distributions are frequently evaluated by discrimination measures, we find that the method for doing so is rarely described in the literature and often leads to unfair comparisons or 'C-hacking'. We demonstrate by example how simple it can be to manipulate results and use this to argue for better reporting guidelines and transparency in the literature. We recommend that machine learning survival analysis software implements clear transformations between distribution and risk predictions in order to allow more transparent and accessible model evaluation. AVAILABILITY AND IMPLEMENTATION: The code used in the final experiment is available at https://github.com/RaphaelS1/distribution_discrimination.

The state of diabetes care and obstacles to better care in Aceh, Indonesia: a mixed-methods study.

BACKGROUND: Cardio-metabolic diseases are a major cause of death worldwide, including in Indonesia, where diabetes is one of the most critical diseases for the health system to manage. METHODS: We describe the characteristics, levels of control, health behavior, and diabetes-related complications of diabetes patients in Aceh, Indonesia. We use baseline data and blood testing from a randomized-controlled trial. We conducted semi-structured interviews with eight health providers from Posbindu and Prolanis programs that target diabetes and other non-communicable diseases (NCDs). We also conducted three focus group discussions with 24 diabetes patients about their experiences of living with diabetes and the existing support programs. RESULTS: The blood tests revealed average HbA1c levels indicative of poor glycemic control in 75.8 percent of patients and only 20.3 percent were free from any symptoms. Our qualitative findings suggest that patients are diagnosed after diabetes-related symptoms manifest, and that they find it hard to comply with treatment recommendations and lifestyle advice. The existing programs related to NCDs are not tailored to their needs. CONCLUSION: We identify the need to improve diabetes screening to enable earlier treatment and achieve better control of the disease. Among diagnosed patients, there are widespread beliefs about diabetes medication and alternative forms of treatment that need to be addressed in a respectful dialogue between healthcare professionals and patients. Current diabetes screening, treatment and management programs should be revised to meet the needs of the affected population and to better respond to the increasing burden of this disease.

Comparison of causal forest and regression-based approaches to evaluate treatment effect heterogeneity: an application for type 2 diabetes precision medicine.

OBJECTIVE: Precision medicine requires reliable identification of variation in patient-level outcomes with different available treatments, often termed treatment effect heterogeneity. We aimed to evaluate the comparative utility of individualized treatment selection strategies based on predicted individual-level treatment effects from a causal forest machine learning algorithm and a penalized regression model. METHODS: Cohort study characterizing individual-level glucose-lowering response (6 month reduction in HbA1c) in people with type 2 diabetes initiating SGLT2-inhibitor or DPP4-inhibitor therapy. Model development set comprised 1,428 participants in the CANTATA-D and CANTATA-D2 randomised clinical trials of SGLT2-inhibitors versus DPP4-inhibitors. For external validation, calibration of observed versus predicted differences in HbA1c in patient strata defined by size of predicted HbA1c benefit was evaluated in 18,741 patients in UK primary care (Clinical Practice Research Datalink). RESULTS: Heterogeneity in treatment effects was detected in clinical trial participants with both approaches (proportion predicted to have a benefit on SGLT2-inhibitor therapy over DPP4-inhibitor therapy: causal forest: 98.6%; penalized regression: 81.7%). In validation, calibration was good with penalized regression but sub-optimal with causal forest. A strata with an HbA1c benefit > 10 mmol/mol with SGLT2-inhibitors (3.7% of patients, observed benefit 11.0 mmol/mol [95%CI 8.0-14.0]) was identified using penalized regression but not causal forest, and a much larger strata with an HbA1c benefit 5-10 mmol with SGLT2-inhibitors was identified with penalized regression (regression: 20.9% of patients, observed benefit 7.8 mmol/mol (95%CI 6.7-8.9); causal forest 11.6%, observed benefit 8.7 mmol/mol (95%CI 7.4-10.1). CONCLUSIONS: Consistent with recent results for outcome prediction with clinical data, when evaluating treatment effect heterogeneity researchers should not rely on causal forest or other similar machine learning algorithms alone, and must compare outputs with standard regression, which in this evaluation was superior.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Variation in the Proportion of Adults in Need of Blood Pressure-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1 037 215 Individuals From 50 Nationally Representative Surveys.

BACKGROUND: Current hypertension guidelines vary substantially in their definition of who should be offered blood pressure-lowering medications. Understanding the effect of guideline choice on the proportion of adults who require treatment is crucial for planning and scaling up hypertension care in low- and middle-income countries. METHODS: We extracted cross-sectional data on age, sex, blood pressure, hypertension treatment and diagnosis status, smoking, and body mass index for adults 30 to 70 years of age from nationally representative surveys in 50 low- and middle-income countries (N = 1 037 215). We aimed to determine the effect of hypertension guideline choice on the proportion of adults in need of blood pressure-lowering medications. We considered 4 hypertension guidelines: the 2017 American College of Cardiology/American Heart Association guideline, the commonly used 140/90 mm Hg threshold, the 2016 World Health Organization HEARTS guideline, and the 2019 UK National Institute for Health and Care Excellence guideline. RESULTS: The proportion of adults in need of blood pressure-lowering medications was highest under the American College of Cardiology/American Heart Association, followed by the 140/90 mm Hg, National Institute for Health and Care Excellence, and World Health Organization guidelines (American College of Cardiology/American Heart Association: women, 27.7% [95% CI, 27.2-28.2], men, 35.0% [95% CI, 34.4-35.7]; 140/90 mm Hg: women, 26.1% [95% CI, 25.5-26.6], men, 31.2% [95% CI, 30.6-31.9]; National Institute for Health and Care Excellence: women, 11.8% [95% CI, 11.4-12.1], men, 15.7% [95% CI, 15.3-16.2]; World Health Organization: women, 9.2% [95% CI, 8.9-9.5], men, 11.0% [95% CI, 10.6-11.4]). Individuals who were unaware that they have hypertension were the primary contributor to differences in the proportion needing treatment under different guideline criteria. Differences in the proportion needing blood pressure-lowering medications were largest in the oldest (65-69 years) age group (American College of Cardiology/American Heart Association: women, 60.2% [95% CI, 58.8-61.6], men, 70.1% [95% CI, 68.8-71.3]; World Health Organization: women, 20.1% [95% CI, 18.8-21.3], men, 24.1.0% [95% CI, 22.3-25.9]). For both women and men and across all guidelines, countries in the European and Eastern Mediterranean regions had the highest proportion of adults in need of blood pressure-lowering medicines, whereas the South and Central Americas had the lowest. CONCLUSIONS: There was substantial variation in the proportion of adults in need of blood pressure-lowering medications depending on which hypertension guideline was used. Given the great implications of this choice for health system capacity, policy makers will need to carefully consider which guideline they should adopt when scaling up hypertension care in their country.

Body-mass index and diabetes risk in 57 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 685 616 adults.

BACKGROUND: The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings. METHODS: In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA1c]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA1c of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5-22·9 kg/m2], upper-normal [23·0-24·9 kg/m2], overweight [25·0-29·9 kg/m2], or obese [≥30·0 kg/m2]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region. FINDINGS: Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6-27·8), of obesity was 21·0% (19·6-22·5), and of diabetes was 9·3% (8·4-10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m2 or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5-22·9 kg/m2. Diabetes risk also increased steeply in individuals aged 35-44 years and in men aged 25-34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m2 among men in east, south, and southeast Asia to 28·3 kg/m2 among women in the Middle East and north Africa and in Latin America and the Caribbean. INTERPRETATION: The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.

Global economic burden of unmet surgical need for appendicitis.

BACKGROUND: There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. METHODS: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. RESULTS: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and $73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and $75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. CONCLUSION: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially.

Maternal iron-and-folic-acid supplementation and its association with low-birth weight and neonatal mortality in India.

OBJECTIVE: The current study assessed intake of iron-and-folic-acid (IFA) tablet/syrup (grouped into none, < 100 d of IFA consumption or < 100 IFA and ≥ 100 d of IFA consumption or ≥ 100 IFA) among prospective mothers and its association with various stages of low-birth weight (ELBW, extremely low-birth weight; VLBW, very low-birth weight and LBW, low-birth weight) and neonatal mortality (death during day 0-1, 2-6, 7-27 and 0-27) in India. DESIGN: The cross-sectional, nationally representative, 2015-2016 National Family Health Survey (NFHS-4) data were used. Weighted descriptive analysis and multiple binary logistic regression modelling were used. SETTING: NFHS-4 covered 640 districts from thirty-seven states and union territories of India. PARTICIPANTS: A total of 120 374 and 143 675 index children aged 0-59 months were included to analyse LBW and neonatal mortality, respectively. RESULTS: Overall, 30·7 % mothers consumed ≥ 100 IFA in 2015-2016, and this estimate ranged from 0·0 % in Zunheboto district of Nagaland state to 89·5 % in Mahe district of Puducherry of India. Multiple regression analysis revealed that children of mothers who consumed ≥ 100 IFA had lower odds of ELBW, VLBW, LBW and neonatal mortality during day 0-1, as compared with mothers who did not buy/receive any IFA. Consumption of IFA (< 100 IFA and ≥ 100 IFA) had a protective association with neonatal death during day 7-27 and 0-27. Consumption of IFA was not associated with neonatal death during day 2-6. CONCLUSIONS: While ≥ 100 IFA consumption during pregnancy was found to be associated with preventing select types of LBW and neonatal mortality, a large variation in coverage of ≥ 100 IFA consumption across 640 districts is concerning.

Unmet need for hypercholesterolemia care in 35 low- and middle-income countries: A cross-sectional study of nationally representative surveys.

BACKGROUND: As the prevalence of hypercholesterolemia is increasing in low- and middle-income countries (LMICs), detailed evidence is urgently needed to guide the response of health systems to this epidemic. This study sought to quantify unmet need for hypercholesterolemia care among adults in 35 LMICs. METHODS AND FINDINGS: We pooled individual-level data from 129,040 respondents aged 15 years and older from 35 nationally representative surveys conducted between 2009 and 2018. Hypercholesterolemia care was quantified using cascade of care analyses in the pooled sample and by region, country income group, and country. Hypercholesterolemia was defined as (i) total cholesterol (TC) ≥240 mg/dL or self-reported lipid-lowering medication use and, alternatively, as (ii) low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dL or self-reported lipid-lowering medication use. Stages of the care cascade for hypercholesterolemia were defined as follows: screened (prior to the survey), aware of diagnosis, treated (lifestyle advice and/or medication), and controlled (TC <200 mg/dL or LDL-C <130 mg/dL). We further estimated how age, sex, education, body mass index (BMI), current smoking, having diabetes, and having hypertension are associated with cascade progression using modified Poisson regression models with survey fixed effects. High TC prevalence was 7.1% (95% CI: 6.8% to 7.4%), and high LDL-C prevalence was 7.5% (95% CI: 7.1% to 7.9%). The cascade analysis showed that 43% (95% CI: 40% to 45%) of study participants with high TC and 47% (95% CI: 44% to 50%) with high LDL-C ever had their cholesterol measured prior to the survey. About 31% (95% CI: 29% to 33%) and 36% (95% CI: 33% to 38%) were aware of their diagnosis; 29% (95% CI: 28% to 31%) and 33% (95% CI: 31% to 36%) were treated; 7% (95% CI: 6% to 9%) and 19% (95% CI: 18% to 21%) were controlled. We found substantial heterogeneity in cascade performance across countries and higher performances in upper-middle-income countries and the Eastern Mediterranean, Europe, and Americas. Lipid screening was significantly associated with older age, female sex, higher education, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Awareness of diagnosis was significantly associated with older age, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Lastly, treatment of hypercholesterolemia was significantly associated with comorbid hypertension and diabetes, and control of lipid measures with comorbid diabetes. The main limitations of this study are a potential recall bias in self-reported information on received health services as well as diminished comparability due to varying survey years and varying lipid guideline application across country and clinical settings. CONCLUSIONS: Cascade performance was poor across all stages, indicating large unmet need for hypercholesterolemia care in this sample of LMICs-calling for greater policy and research attention toward this cardiovascular disease (CVD) risk factor and highlighting opportunities for improved prevention of CVD.

Cardiovascular disease risk profile and management practices in 45 low-income and middle-income countries: A cross-sectional study of nationally representative individual-level survey data.

BACKGROUND: Global cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population's median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines. METHODS AND FINDINGS: We conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%-4.2%) and 1.6% (1.3%-2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%-37.2%) for males and 41.6% (23.9%-53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%-58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis. CONCLUSIONS: This study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.

The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.

BACKGROUND: The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain. METHODS: A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease). RESULTS: One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)]. CONCLUSION: Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.

Improving Survival of Critical Care Patients With Coronavirus Disease 2019 in England: A National Cohort Study, March to June 2020.

OBJECTIVES: To measure temporal trends in survival over time in people with severe coronavirus disease 2019 requiring critical care (high dependency unit or ICU) management, and to assess whether temporal variation in mortality was explained by changes in patient demographics and comorbidity burden over time. DESIGN: Retrospective observational cohort; based on data reported to the COVID-19 Hospitalisation in England Surveillance System. The primary outcome was in-hospital 30-day all-cause mortality. Unadjusted survival was estimated by calendar week of admission, and Cox proportional hazards models were used to estimate adjusted survival, controlling for age, sex, ethnicity, major comorbidities, and geographical region. SETTING: One hundred eight English critical care units. PATIENTS: All adult (18 yr +) coronavirus disease 2019 specific critical care admissions between March 1, 2020, and June 27, 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Twenty-one thousand eighty-two critical care patients (high dependency unit n = 15,367; ICU n = 5,715) were included. Unadjusted survival at 30 days was lowest for people admitted in late March in both high dependency unit (71.6% survival) and ICU (58.0% survival). By the end of June, survival had improved to 92.7% in high dependency unit and 80.4% in ICU. Improvements in survival remained after adjustment for patient characteristics (age, sex, ethnicity, and major comorbidities) and geographical region. CONCLUSIONS: There has been a substantial improvement in survival amongst people admitted to critical care with coronavirus disease 2019 in England, with markedly higher survival rates in people admitted in May and June compared with those admitted in March and April. Our analysis suggests this improvement is not due to temporal changes in the age, sex, ethnicity, or major comorbidity burden of admitted patients.

Trends in 28-Day Mortality of Critical Care Patients With Coronavirus Disease 2019 in the United Kingdom: A National Cohort Study, March 2020 to January 2021.

OBJECTIVES: To determine whether the previously described trend of improving mortality in people with coronavirus disease 2019 in critical care during the first wave was maintained, plateaued, or reversed during the second wave in United Kingdom, when B117 became the dominant strain. DESIGN: National retrospective cohort study. SETTING: All English hospital trusts (i.e., groups of hospitals functioning as single operational units), reporting critical care admissions (high dependency unit and ICU) to the Coronavirus Disease 2019 Hospitalization in England Surveillance System. PATIENTS: A total of 49,862 (34,336 high dependency unit and 15,526 ICU) patients admitted between March 1, 2020, and January 31, 2021 (inclusive). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: The primary outcome was inhospital 28-day mortality by calendar month of admission, from March 2020 to January 2021. Unadjusted mortality was estimated, and Cox proportional hazard models were used to estimate adjusted mortality, controlling for age, sex, ethnicity, major comorbidities, social deprivation, geographic location, and operational strain (using bed occupancy as a proxy). Mortality fell to trough levels in June 2020 (ICU: 22.5% [95% CI, 18.2-27.4], high dependency unit: 8.0% [95% CI, 6.4-9.6]) but then subsequently increased up to January 2021: (ICU: 30.6% [95% CI, 29.0-32.2] and high dependency unit, 16.2% [95% CI, 15.3-17.1]). Comparing patients admitted during June-September 2020 with those admitted during December 2020-January 2021, the adjusted mortality was 59% (CI range, 39-82) higher in high dependency unit and 88% (CI range, 62-118) higher in ICU for the later period. This increased mortality was seen in all subgroups including those under 65. CONCLUSIONS: There was a marked deterioration in outcomes for patients admitted to critical care at the peak of the second wave of coronavirus disease 2019 in United Kingdom (December 2020-January 2021), compared with the post-first-wave period (June 2020-September 2020). The deterioration was independent of recorded patient characteristics and occupancy levels. Further research is required to determine to what extent this deterioration reflects the impact of the B117 variant of concern.

The Impact of Immediate Initiation of Antiretroviral Therapy on Patients' Healthcare Expenditures: A Stepped-Wedge Randomized Trial in Eswatini.

Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients' healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients' healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization's recommendation to abolish CD4-count-based eligibility thresholds for ART.

RESUMEN: El inicio inmediato de la terapia antirretroviral (TAR) para todas las personas que viven con VIH tiene importantes beneficios para la salud, pero aún se desconocen las implicaciones en el aspecto económico. Este ensayo controlado aleatorizado por clústers (CRT por sus siglas en inglés) por grupos en distintas etapas pretende determinar el impacto del inicio inmediato de la TAR en los gastos sanitarios de los pacientes en Eswatini. Catorce centros sanitarios fueron asignados aleatoriamente a la transición en uno de los siete periodos de la asistencia estándar (elegibilidad para la TAR en niveles definidos de recuento de CD4) a la intervención de TAR inmediato para todos (EAAA). Se entrevistó a 2.261 pacientes con VIH a lo largo del estudio para conocer sus gastos sanitarios del año anterior. Según los modelos de regresión de efectos mixtos, se observó un descenso del 49% (RR: 0,51; IC del 95%: 0,36, 0,72; p<0,001) en el gasto sanitario total del año anterior en el grupo de la EAAA, y un descenso del 98% (RR 0,02; IC del 95%: 0,00, 0,02; p<0,001) en el gasto en asistencia sanitaria privada y tradicional. A pesar de una mayor frecuencia de visitas deatención de VIH para los pacientes que recién comenzaron laTAR, la aplicación inmediata de laTAR redujo los gastos sanitarios de los pacientes dado que buscaron menos atención de proveedores de asistencia sanitaria alternativos. Este estudio añade un importante argumento económico a la recomendación de la Organización Mundial de la Salud de abolir las restricciones de elegibilidad para la terapia antirretroviral basados en el recuento de CD4.

Predictors of patients' choice of hospitals under universal health coverage: a case study of the Nicaraguan capital.

BACKGROUND: This study looks at the factors that can shape patients' choice of healthcare providers. Understanding this process can help with making high quality healthcare more accessible for all. We focus on distance, patient's health status, (perceived) quality of healthcare facility, and referrals to investigate how these factors compete in shaping patients' choice of hospitals. METHODS: This study was carried out in Managua, the capital of Nicaragua. Utilizing an exit-survey, patients were interviewed across five public hospitals in 2017 and then six in 2019 when a new highly-equipped hospital was added to the system. We used a multinomial logit model to investigate patients' preference of a specific hospital over the rest within each wave. RESULTS: Our results show that being referred to a hospital is the strongest predictor and in some cases, it can increase the relative risk ratio of choosing a facility by a factor of 49 (p < 0.01; 95% CI: 27.39-87.17). For the remaining factors, the hierarchy of importance was less clear-cut yet all these factors remained significantly important at various levels. CONCLUSIONS: Overall, our results highlight the importance of referral systems in making quality healthcare more equitable. Moreover, with distance also being a key predictor and in the absence of an organized referral system, those with low-income would either be further deprived by having to settle with locally available healthcare (regardless of its quality) or face high amounts of out-of-pocket expenditure when seeking help from the private sector.

Association between country preparedness indicators and quality clinical care for cardiovascular disease risk factors in 44 lower- and middle-income countries: A multicountry analysis of survey data.

BACKGROUND: Cardiovascular diseases are leading causes of death, globally, and health systems that deliver quality clinical care are needed to manage an increasing number of people with risk factors for these diseases. Indicators of preparedness of countries to manage cardiovascular disease risk factors (CVDRFs) are regularly collected by ministries of health and global health agencies. We aimed to assess whether these indicators are associated with patient receipt of quality clinical care. METHODS AND FINDINGS: We did a secondary analysis of cross-sectional, nationally representative, individual-patient data from 187,552 people with hypertension (mean age 48.1 years, 53.5% female) living in 43 low- and middle-income countries (LMICs) and 40,795 people with diabetes (mean age 52.2 years, 57.7% female) living in 28 LMICs on progress through cascades of care (condition diagnosed, treated, or controlled) for diabetes or hypertension, to indicate outcomes of provision of quality clinical care. Data were extracted from national-level World Health Organization (WHO) Stepwise Approach to Surveillance (STEPS), or other similar household surveys, conducted between July 2005 and November 2016. We used mixed-effects logistic regression to estimate associations between each quality clinical care outcome and indicators of country development (gross domestic product [GDP] per capita or Human Development Index [HDI]); national capacity for the prevention and control of noncommunicable diseases ('NCD readiness indicators' from surveys done by WHO); health system finance (domestic government expenditure on health [as percentage of GDP], private, and out-of-pocket expenditure on health [both as percentage of current]); and health service readiness (number of physicians, nurses, or hospital beds per 1,000 people) and performance (neonatal mortality rate). All models were adjusted for individual-level predictors including age, sex, and education. In an exploratory analysis, we tested whether national-level data on facility preparedness for diabetes were positively associated with outcomes. Associations were inconsistent between indicators and quality clinical care outcomes. For hypertension, GDP and HDI were both positively associated with each outcome. Of the 33 relationships tested between NCD readiness indicators and outcomes, only two showed a significant positive association: presence of guidelines with being diagnosed (odds ratio [OR], 1.86 [95% CI 1.08-3.21], p = 0.03) and availability of funding with being controlled (OR, 2.26 [95% CI 1.09-4.69], p = 0.03). Hospital beds (OR, 1.14 [95% CI 1.02-1.27], p = 0.02), nurses/midwives (OR, 1.24 [95% CI 1.06-1.44], p = 0.006), and physicians (OR, 1.21 [95% CI 1.11-1.32], p < 0.001) per 1,000 people were positively associated with being diagnosed and, similarly, with being treated; and the number of physicians was additionally associated with being controlled (OR, 1.12 [95% CI 1.01-1.23], p = 0.03). For diabetes, no positive associations were seen between NCD readiness indicators and outcomes. There was no association between country development, health service finance, or health service performance and readiness indicators and any outcome, apart from GDP (OR, 1.70 [95% CI 1.12-2.59], p = 0.01), HDI (OR, 1.21 [95% CI 1.01-1.44], p = 0.04), and number of physicians per 1,000 people (OR, 1.28 [95% CI 1.09-1.51], p = 0.003), which were associated with being diagnosed. Six countries had data on cascades of care and nationwide-level data on facility preparedness. Of the 27 associations tested between facility preparedness indicators and outcomes, the only association that was significant was having metformin available, which was positively associated with treatment (OR, 1.35 [95% CI 1.01-1.81], p = 0.04). The main limitation was use of blood pressure measurement on a single occasion to diagnose hypertension and a single blood glucose measurement to diagnose diabetes. CONCLUSION: In this study, we observed that indicators of country preparedness to deal with CVDRFs are poor proxies for quality clinical care received by patients for hypertension and diabetes. The major implication is that assessments of countries' preparedness to manage CVDRFs should not rely on proxies; rather, it should involve direct assessment of quality clinical care.

The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults.

BACKGROUND: Evidence from nationally representative studies in low-income and middle-income countries (LMICs) on where in the hypertension care continuum patients are lost to care is sparse. This information, however, is essential for effective targeting of interventions by health services and monitoring progress in improving hypertension care. We aimed to determine the cascade of hypertension care in 44 LMICs-and its variation between countries and population groups-by dividing the progression in the care process, from need of care to successful treatment, into discrete stages and measuring the losses at each stage. METHODS: In this cross-sectional study, we pooled individual-level population-based data from 44 LMICs. We first searched for nationally representative datasets from the WHO Stepwise Approach to Surveillance (STEPS) from 2005 or later. If a STEPS dataset was not available for a LMIC (or we could not gain access to it), we conducted a systematic search for survey datasets; the inclusion criteria in these searches were that the survey was done in 2005 or later, was nationally representative for at least three 10-year age groups older than 15 years, included measured blood pressure data, and contained data on at least two hypertension care cascade steps. Hypertension was defined as a systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or reported use of medication for hypertension. Among those with hypertension, we calculated the proportion of individuals who had ever had their blood pressure measured; had been diagnosed with hypertension; had been treated for hypertension; and had achieved control of their hypertension. We weighted countries proportionally to their population size when determining this hypertension care cascade at the global and regional level. We disaggregated the hypertension care cascade by age, sex, education, household wealth quintile, body-mass index, smoking status, country, and region. We used linear regression to predict, separately for each cascade step, a country's performance based on gross domestic product (GDP) per capita, allowing us to identify countries whose performance fell outside of the 95% prediction interval. FINDINGS: Our pooled dataset included 1 100 507 participants, of whom 192 441 (17·5%) had hypertension. Among those with hypertension, 73·6% of participants (95% CI 72·9-74·3) had ever had their blood pressure measured, 39·2% of participants (38·2-40·3) had been diagnosed with hypertension, 29·9% of participants (28·6-31·3) received treatment, and 10·3% of participants (9·6-11·0) achieved control of their hypertension. Countries in Latin America and the Caribbean generally achieved the best performance relative to their predicted performance based on GDP per capita, whereas countries in sub-Saharan Africa performed worst. Bangladesh, Brazil, Costa Rica, Ecuador, Kyrgyzstan, and Peru performed significantly better on all care cascade steps than predicted based on GDP per capita. Being a woman, older, more educated, wealthier, and not being a current smoker were all positively associated with attaining each of the four steps of the care cascade. INTERPRETATION: Our study provides important evidence for the design and targeting of health policies and service interventions for hypertension in LMICs. We show at what steps and for whom there are gaps in the hypertension care process in each of the 44 countries in our study. We also identified countries in each world region that perform better than expected from their economic development, which can direct policy makers to important policy lessons. Given the high disease burden caused by hypertension in LMICs, nationally representative hypertension care cascades, as constructed in this study, are an important measure of progress towards achieving universal health coverage. FUNDING: Harvard McLennan Family Fund, Alexander von Humboldt Foundation.

Evaluation of sex differences in dietary behaviours and their relationship with cardiovascular risk factors: a cross-sectional study of nationally representative surveys in seven low- and middle-income countries.

BACKGROUND: Cardiovascular diseases (CVD) are the leading causes of death for men and women in low-and-middle income countries (LMIC). The nutrition transition to diets high in salt, fat and sugar and low in fruit and vegetables, in parallel with increasing prevalence of diet-related CVD risk factors in LMICs, identifies the need for urgent action to reverse this trend. To aid identification of the most effective interventions it is crucial to understand whether there are sex differences in dietary behaviours related to CVD risk. METHODS: From a dataset of 46 nationally representative surveys, we included data from seven countries that had recorded the same dietary behaviour measurements in adults; Bhutan, Eswatini, Georgia, Guyana, Kenya, Nepal and St Vincent and the Grenadines (2013-2017). Three dietary behaviours were investigated: positive salt use behaviour (SUB), meeting fruit and vegetable (F&V) recommendations and use of vegetable oil rather than animal fats in cooking. Generalized linear models were used to investigate the association between dietary behaviours and waist circumference (WC) and undiagnosed and diagnosed hypertension and diabetes. Interaction terms between sex and dietary behaviour were added to test for sex differences. RESULTS: Twenty-four thousand three hundred thirty-two participants were included. More females than males reported positive SUB (31.3 vs. 27.2% p-value < 0.001), yet less met F&V recommendations (13.2 vs. 14.8%, p-value< 0.05). The prevalence of reporting all three dietary behaviours in a positive manner was 2.7%, varying by country, but not sex. Poor SUB was associated with a higher prevalence of undiagnosed hypertension for females (13.1% vs. 9.9%, p-value = 0.04), and a higher prevalence of undiagnosed diabetes for males (2.4% vs. 1.5%, p-value = 0.02). Meeting F&V recommendations was associated with a higher prevalence of high WC (24.4% vs 22.6%, p-value = 0.01), but was not associated with undiagnosed or diagnosed hypertension or diabetes. CONCLUSION: Interventions to increase F&V intake and positive SUBs in the included countries are urgently needed. Dietary behaviours were not notably different between sexes. However, our findings were limited by the small proportion of the population reporting positive dietary behaviours, and further research is required to understand whether associations with CVD risk factors and interactions by sex would change as the prevalence of positive behaviours increases.

Lifetime Prevalence of Cervical Cancer Screening in 55 Low- and Middle-Income Countries.

Importance: The World Health Organization is developing a global strategy to eliminate cervical cancer, with goals for screening prevalence among women aged 30 through 49 years. However, evidence on prevalence levels of cervical cancer screening in low- and middle-income countries (LMICs) is sparse. Objective: To determine lifetime cervical cancer screening prevalence in LMICs and its variation across and within world regions and countries. Design, Setting, and Participants: Analysis of cross-sectional nationally representative household surveys carried out in 55 LMICs from 2005 through 2018. The median response rate across surveys was 93.8% (range, 64.0%-99.3%). The population-based sample consisted of 1 136 289 women aged 15 years or older, of whom 6885 (0.6%) had missing information for the survey question on cervical cancer screening. Exposures: World region, country; countries' economic, social, and health system characteristics; and individuals' sociodemographic characteristics. Main Outcomes and Measures: Self-report of having ever had a screening test for cervical cancer. Results: Of the 1 129 404 women included in the analysis, 542 475 were aged 30 through 49 years. A country-level median of 43.6% (interquartile range [IQR], 13.9%-77.3%; range, 0.3%-97.4%) of women aged 30 through 49 years self-reported to have ever been screened, with countries in Latin America and the Caribbean having the highest prevalence (country-level median, 84.6%; IQR, 65.7%-91.1%; range, 11.7%-97.4%) and those in sub-Saharan Africa the lowest prevalence (country-level median, 16.9%; IQR, 3.7%-31.0%; range, 0.9%-50.8%). There was large variation in the self-reported lifetime prevalence of cervical cancer screening among countries within regions and among countries with similar levels of per capita gross domestic product and total health expenditure. Within countries, women who lived in rural areas, had low educational attainment, or had low household wealth were generally least likely to self-report ever having been screened. Conclusions and Relevance: In this cross-sectional study of data collected in 55 low- and middle-income countries from 2005 through 2018, there was wide variation between countries in the self-reported lifetime prevalence of cervical cancer screening. However, the median prevalence was only 44%, supporting the need to increase the rate of screening.