METHODS: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively.
FINDINGS: In 2021, there were 529 million (95% uncertainty interval [UI] 500-564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8-6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7-9·9]) and, at the regional level, in Oceania (12·3% [11·5-13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1-79·5) in individuals aged 75-79 years. Total diabetes prevalence-especially among older adults-primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1-96·8) of diabetes cases and 95·4% (94·9-95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5-71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5-30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22-1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1-17·6) in north Africa and the Middle East and 11·3% (10·8-11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%.
INTERPRETATION: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers.
FUNDING: Bill & Melinda Gates Foundation.
RESULTS: The spatial model with split random effects and a common intercept has the lowest Deviance and Watanabe Information Criteria. There was evidence of a spatial pattern in the prevalence of childhood overweight across districts. An increasing trend in smoothed prevalence of overweight was observed when moving from the east to the west of the Peninsular and Borneo regions. The proportion of Bumiputera ethnicity in the district had a significant negative association with childhood overweight: the higher the proportion of Bumiputera ethnicity in the district, the lower the prevalence of childhood overweight.
CONCLUSION: This study illustrates different available techniques for mapping prevalence across districts in disconnected regions using survey data. These techniques can be utilized to produce reliable subnational estimates for any areas that comprise of disconnected regions. Through the example, we learned that the best-fit model was the one that considered the separate variations of the individual regions. We discovered that the occurrence of childhood overweight in Malaysia followed a spatial pattern with an east-west gradient trend, and we identified districts with high prevalence of overweight. This information could help policy makers in making informed decisions for targeted public health interventions in high-risk areas.
METHODS: This protocol was drafted in agreement with the ROBUST-statement, and is submitted for publication before database lock and primary data analysis. The primary outcome is health-related quality of life as measured by the EQ-5D-5L health utility score and is longitudinally assessed. Secondary outcomes comprise the 6-min walking test and handgrip strength over the entire follow-up period (longitudinal analyses), and 60-day mortality, duration of mechanical ventilation, and EQ-5D-5L health utility scores at 30, 90 and 180 days (cross-sectional). All analyses will primarily be performed under weakly informative priors. When available, informative priors elicited from contemporary literature will also be incorporated under alternative scenarios. In all other cases, objectively formulated skeptical and enthusiastic priors will be defined to assess the robustness of our results. Relevant identified subgroups were: patients with acute kidney injury, severe multi-organ failure and patients with or without sepsis. Results will be presented as absolute risk differences, mean differences, and odds ratios, with accompanying 95% credible intervals. Posterior probabilities will be estimated for clinically important benefit and harm.
DISCUSSION: The proposed secondary, pre-planned Bayesian analysis of the PRECISe trial will provide additional information on the effects of high protein on functional and clinical outcomes in critically ill patients, such as probabilistic interpretation, probabilities of clinically important effect sizes, and the integration of prior evidence. As such, it will complement the interpretation of the primary outcome as well as several secondary and subgroup analyses.
METHODS: Using parasite clearance data from 714 patients with knowlesi malaria and enrolled in three trials, the Worldwide Antimalarial Resistance Network (WWARN) Parasite Clearance Estimator (PCE) standard two-stage approach and Bayesian hierarchical modelling were compared. Both methods estimate the parasite clearance rate from a model that incorporates a lag phase, slope, and tail phase for the parasitaemia profiles.
RESULTS: The standard two-stage approach successfully estimated the parasite clearance rate for 678 patients, with 36 (5%) patients excluded due to an insufficient number of available parasitaemia measurements. The Bayesian hierarchical estimation method was applied to the parasitaemia data of all 714 patients. Overall, the Bayesian method estimated a faster population mean parasite clearance (0.36/h, 95% credible interval [0.18, 0.65]) compared to the standard two-stage method (0.26/h, 95% confidence interval [0.11, 0.46]), with better model fits (compared visually). Artemisinin-based combination therapy (ACT) is more effective in treating P. knowlesi than chloroquine, as confirmed by both methods, with a mean estimated parasite clearance half-life of 2.5 and 3.6 h, respectively using the standard two-stage method, and 1.8 and 2.9 h using the Bayesian method.
CONCLUSION: For clinical studies of P. knowlesi with frequent parasite measurements, the standard two-stage approach (WWARN's PCE) is recommended as this method is straightforward to implement. For studies with fewer parasite measurements per patient, the Bayesian approach should be considered. Regardless of method used, ACT is more efficacious than chloroquine, confirming the findings of the original trials.
METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC50 and LC99, respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI50 and OI99), to measure mortality and the sterilizing effect, respectively.
RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC50/LC99 or OI50/OI99 values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were
OBJECTIVE: This study aims to conduct a comprehensive analysis of machine learning (ML) methods for MRI-based biomarker selection and classification to investigate early cognitive decline in AD. The focus to discriminate between classifying healthy control (HC) participants who remained stable and those who developed mild cognitive impairment (MCI) within five years (unstable HC or uHC).
METHODS: 3-Tesla (3T) MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies 3 (OASIS-3) were used, focusing on HC and uHC groups. Freesurfer's recon-all and other tools were used to extract anatomical biomarkers from subcortical and cortical brain regions. ML techniques were applied for feature selection and classification, using the MATLAB Classification Learner (MCL) app for initial analysis, followed by advanced methods such as nested cross-validation and Bayesian optimization, which were evaluated within a Monte Carlo replication analysis as implemented in our customized pipeline. Additionally, polynomial regression-based data harmonization techniques were used to enhance ML and statistical analysis. In our study, ML classifiers were evaluated using performance metrics such as Accuracy (Acc), area under the receiver operating characteristic curve (AROC), F1-score, and a normalized Matthew's correlation coefficient (MCC').
RESULTS: Feature selection consistently identified biomarkers across ADNI and OASIS-3, with the entorhinal, hippocampus, lateral ventricle, and lateral orbitofrontal regions being the most affected. Classification results varied between balanced and imbalanced datasets and between ADNI and OASIS-3. For ADNI balanced datasets, the naíve Bayes model using z-score harmonization and ReliefF feature selection performed best (Acc = 69.17%, AROC = 77.73%, F1 = 69.21%, MCC' = 69.28%). For OASIS-3 balanced datasets, SVM with zscore-corrected data outperformed others (Acc = 66.58%, AROC = 72.01%, MCC' = 66.78%), while logistic regression had the best F1-score (66.68%). In imbalanced data, RUSBoost showed the strongest overall performance on ADNI (F1 = 50.60%, AROC = 81.54%) and OASIS-3 (MCC' = 63.31%). Support vector machine (SVM) excelled on ADNI in terms of Acc (82.93%) and MCC' (70.21%), while naïve Bayes performed best on OASIS-3 by F1 (42.54%) and AROC (70.33%).
CONCLUSION: Data harmonization significantly improved the consistency and performance of feature selection and ML classification, with z-score harmonization yielding the best results. This study also highlights the importance of nested cross-validation (CV) to control overfitting and the potential of a semi-automatic pipeline for early AD detection using MRI, with future applications integrating other neuroimaging data to enhance prediction.