To estimate all cause mortality among children, adolescents, and youths aged 5-24 years for 200 countries and areas from 1990 to 2024, to assess mortality levels and trends, and to identify which regions and countries require the greatest investment. Database construction of empirical data on mortality, mortality estimation, and assessment of levels and trends. Mortality databases were constructed from all available nationally representative data including vital registration data, sample vital registration data, household surveys, and population censuses to estimate mortality risk in the age groups in people aged 5 to 24 years. In 2024, an estimated 2.1 million (90% uncertainty interval (UI) 2.1 million to 2.4 million) people aged 5-24 years died worldwide, representing 31% of all 7.0 million deaths under 25 years of age. This figure, an increase from 21% (3.3 million of 16.3 million) in 1990, reflects this age group's increasing epidemiological importance as mortality in children under 5 years old declines faster. Globally, mortality risk was lowest at ages 10-14 years (2.7 (90% UI 2.5 to 3.3) deaths per 1000) and increased at ages 15-19 years (4.3 (4.1 to 4.6)) and 20-24 years (6.1 (5.7 to 7.7)). Male mortality was consistently higher than female mortality, with the male to female ratio increasing with age. Progress has been uneven: mortality fell by 64% for people aged 5-9 years from 1990 to 2024, compared with 33% for people aged 20-24 years, with slower declines in male mortality, particularly in older youth (26% reduction in male mortality v a 43% reduction in female mortality in people aged 20-24 years). Mortality declines have slowed since 2015, with increases in some low mortality regions, including North America, in people aged 10-24 years. In West and Central Africa, population growth outpaced mortality decline, increasing the absolute number of deaths. Deaths were increasingly concentrated in high mortality regions. Nearly half of deaths in 2024 occurred in just two regions: West and Central Africa, and Eastern and Southern Africa, which accounted for 23% (0.6 billion of 2.6 billion) of the global population of 5-24 year olds. This figure is an increase from 12% in 1990 (0.2 billion of 2.1 billion) and is projected to exceed 30% (0.9 billion of 2.6 billion) by 2050. Progress in reducing mortality in people aged 5-24 years has been uneven and has slowed. Urgent, context specific investments-particularly in high mortality regions-are needed to reduce preventable deaths and strengthen mortality monitoring data systems.
Psoriatic disease, including psoriasis and psoriatic arthritis, is associated with increased risk of comorbidities (cardiovascular disease, mental health disorders, type 2 diabetes mellitus and obesity), placing substantial burden on patients and health systems. We aimed to quantify the lifetime economic burden of these four comorbidities in populations with moderate-to-severe psoriasis and psoriatic arthritis. We subsequently estimated the potential comorbidity-related gross cost offsets from timely systemic therapy across three diverse country settings (Denmark, the USA and Vietnam). We conducted a literature review to identify data on prevalence, comorbidity risk, treatment-associated risk reduction and cost inputs, followed by development of a static cohort-based economic model from a societal perspective. The model compared untreated/undertreated moderate-to-severe psoriasis/psoriatic arthritis; and systemic treatment scenarios (conventional systemic disease-modifying antirheumatic drugs [csDMARDs]; biologic DMARDs [bDMARDs]; and targeted synthetic DMARDs [tsDMARDs]) over a lifetime horizon in Denmark, the USA and Vietnam, reporting total comorbidity cost offsets across direct (healthcare) and indirect (societal) costs. Systemic treatment reduced lifetime comorbidity-related direct and societal costs across settings. In the USA, patients with moderate-to-severe psoriasis incurred annual direct costs of approximately 4.6 billion USD (indirect 0.6 billion USD), and untreated lifetime burden of about 153.0 billion USD. Treating all patients with bDMARDs yielded an estimated cost offset of 62.9 billion USD in the direct costs and an offset of 8.1 billion USD in the societal costs compared with a fully undertreated population. Equivalent analyses in Denmark and Vietnam reflected similar effects on comorbidity-related costs. The model shows that early systemic therapy yields substantial effect on the direct and societal costs via reduced comorbidity incidence. Timely and efficacious systemic treatment of psoriatic disease can significantly reduce lifetime economic burden of comorbidities across diverse healthcare settings. These findings underscore the value of early, proactive management of psoriatic disease and highlight the need for further cost-effectiveness research, including treatment uptake and real-world comorbidity prevention. Could early systemic treatment reduce the costs of comorbidities linked to psoriatic disease? Psoriatic disease is a chronic inflammatory disease that includes psoriasis (affecting the skin) and psoriatic arthritis (affecting the joints). People with psoriatic disease are also more likely to develop other serious health problems, known as comorbidities, such as cardiovascular disease, type 2 diabetes, obesity, depression and anxiety. These conditions can greatly affect quality of life and increase healthcare costs. In this study, we examined whether treating psoriatic disease earlier and more effectively with systemic treatments (medications that work throughout the body) could reduce the risk and offset the costs of these comorbidities. We reviewed published studies and developed an economic model to estimate the lifetime cost of comorbidities in people with moderate-to-severe psoriasis and psoriatic arthritis in Denmark, the USA and Vietnam and how this burden may differ with early treatment using conventional systemic, biologic, or targeted synthetic therapies. Our findings suggest that early systemic treatment may lower the risks of comorbidities and reduce long-term healthcare costs. Overall, timely and effective treatment of psoriatic disease may improve symptoms of psoriatic disease while also potentially reducing the economic burden on healthcare systems and society.
Biodiversity loss and deforestation are increasingly recognized as systemic economic risks. Yet, their implications for financial markets remain poorly understood. Here we study how biodiversity and ecosystem service loss affect financial risk for the world's largest asset class, sovereign debt. Environmental degradation undermines the natural foundations of economic activity, reducing productive capacity and the ability of governments to service debt. Currently, sovereign credit ratings ignore these risks, meaning that markets may be mispricing, mismanaging and misallocating US$83 trillion of financial assets. We incorporate biodiversity risk into sovereign credit assessments by extending S&P Global's methodology to include scenarios for future tropical timber, wild pollination and marine fisheries services across 23 countries, representing 5.5 billion people. A partial ecosystem collapse scenario increases annual debt servicing costs by US$49 billion in India, equivalent to 2.4% of median post-tax income, and by US$70 billion in China. Across countries, additional annual interest payments could reach US$162 billion, nearly reaching the US$200 billion per year target for conservation support under the Global Biodiversity Framework. Angola, Bangladesh, the Democratic Republic of the Congo and Madagascar could face gross domestic product losses of more than 15% by 2030. Our results suggest that financial markets are systematically underpricing nature-related risks, with consequences for public finances, nature and financial stability.
Human papilloma virus (HPV), the most prevalent sexually transmitted infection worldwide, and in particular HPV 6 and 11, contribute to >90% of anogenital warts (AGW) cases, and high-risk HPV serotypes cause >95% of cervical cancers in South Africa (SA). The healthcare resource utilisation (HCRU) and costs related to AGW in SA remain poorly understood, in both the public and private sectors. To assess the HCRU patterns and associated treatment costs for AGW across the public and private sectors. A descriptive, questionnaire-based study was conducted, involving 50 subject matter experts (SMEs) from SA: 24 from the private sector and 26 from the public sector. The study explored resource use, treatment patterns and cost estimation based on SME responses. Findings revealed that public-sector SMEs treated a larger volume of AGW patients per month (1 - 300) than private-sector SMEs (0 - 20). Most AGW patients were female, comprising 78% in the public sector and 72% in the private sector. The occurrence of AGW was higher in the public sector, ranging between 21.4% and 34.4%, while in the private sector, the occurrence ranged from 13.1% to 23.2%. The weighted cost per patient per episode was higher for females than males in both sectors. In the private sector, costs were ZAR22 482 for females and ZAR17 812 for males, while in the public sector, costs were ZAR19 220 for females and ZAR14 271 for males. The higher costs for females were driven by invasive diagnostic procedures, including vulvar colposcopy and biopsy, and a higher frequency of medical visits (2.0 - 4.4 visits in the public sector). Recurrence rates of AGW were reported at 37.6% in the private sector and 43.9% in the public sector. The total estimated treatment cost of AGW was notably higher in the public sector for both males (ZAR93.6 - ZAR138.5 billion) and females (ZAR135.2 - ZAR207.7 billion), compared with the private sector (males: ZAR11.0 - ZAR19.4 billion; females: ZAR16.7 - ZAR28.3 billion). Female patients experienced a higher burden of diagnosis, recurrence and complications than males. AGW imposes a substantial burden on SA's healthcare system, particularly in the public sector, where female patients face significant costs and complications. The use of a quadrivalent or nonavalent HPV vaccine, rather than a bivalent vaccine, could reduce the impact of AGW and its associated healthcare demands.
Atmospheric carbon dioxide removal (CDR) is required to stabilize global temperature. CDR can be achieved via ecosystem-based approaches that are cost-effective but reversible (e.g., soil and forest management) or by more durable but expensive approaches (e.g., direct air capture coupled with geologic storage). Here, we examine trade-offs between these approaches, focusing on timing, climate impacts, and cost. We simulated reversible carbon accrual for a range of CDR contract structures using a general minimalist model of ecosystem carbon cycling, and parameterized it to simulate US agricultural soil management─specifically cover cropping─as a case study. We then quantified the resulting impact on atmospheric carbon and global temperature using a climate model emulator. We find that maintaining a patchwork of reversible CDR projects by replacing lapsed projects with new projects can reduce warming by 22-195 μ°C in 2100 and that the magnitude of this cooling effect depends on how effectively the patchwork is maintained. Long-term maintenance of reversible CDR projects requires institutional stability that cannot be guaranteed over multiple decades. Consequently, effective CDR ultimately requires replacing reversible projects with durable projects. To address this problem, we modeled the cost of replacing reversible agricultural soil CDR with geologic CDR. We found that using reversible CDR as a bridge to durable CDR is potentially more cost-effective as a global cooling strategy (0.20-0.81 billion USD per μ°C avoided) than perpetual maintenance of reversible CDR (0.32-1.31 billion USD per μ°C avoided) or an immediate transition to durable CDR (1.37-2.19 billion USD per μ°C avoided). However, we emphasize that institutional commitments to maintain reversible CDR projects cannot be guaranteed. Reliance on reversible CDR as a bridge to durable CDR therefore carries an unknown amount of risk and will only function if efforts to maintain reversible CDR are robust.
This study aims to explore the necessity, model selection, and implementation suggestions for the provincial-level overall planning of basic medical insurance in Guangxi, China, to address the structural imbalance of medical insurance funds and improve the sustainability of the system. A comparative analysis approach was employed to examine the "unified revenue and expenditure" model and the "adjustment fund" model for provincial-level overall planning. Data were collected from official sources, including the 2023 Statistical Communique on the Development of Medical Security in Guangxi and policy documents. The analysis focused on fund balance, demographic structure, and regional disparities in Guangxi. In 2023, the accumulated balance of Guangxi's employee medical insurance pooling fund reached 37.736 billion yuan, and the resident medical insurance fund balance was 43.197 billion yuan. However, significant regional imbalances existed, with the number of months covered by the accumulated balance being 22.40 months for employee insurance and 11.51 months for resident insurance. Cross-regional medical treatments reached 5.888 million visits, costing 19.165 billion yuan, leading to a "siphoning effect" (i.e., the excessive concentration of patients and funds towards medical resource-rich areas) that exacerbated regional disparities. The adjustment fund model is recommended as an initial step for Guangxi, given its flexibility and lower reform resistance. Promoting provincial-level overall planning of basic medical insurance in Guangxi is essential to solve fund imbalances and improve sustainability. The adjustment fund model serves as a transitional approach, with gradual movement toward unified revenue and expenditure. Key suggestions include establishing dual-track adjustment funds, scientific fund extraction rules, and enhancing digital infrastructure.
2024 marked the 50th anniversary of the Expanded Programme on Immunization (EPI), launched by WHO. Despite its crucial role in preventing infectious diseases, EPI's 50-year economic impact has not been systematically evaluated. This study aims to estimate the benefit-cost ratios (BCRs) and incremental cost-effectiveness ratios (ICERs) of EPI at global, regional, and national levels. We conducted an economic evaluation of EPI for 14 globally important pathogens with robust long-term data availability: Corynebacterium diphtheriae (diphtheria), Haemophilus influenzae type b, hepatitis B virus (hepatitis B), Japanese encephalitis virus (Japanese encephalitis), measles virus (measles), Neisseria meningitidis group A (meningitis A), Streptococcus pneumoniae, Bordetella pertussis (pertussis), poliovirus (polio), rotavirus, rubella virus (rubella), Clostridium tetani (tetanus), Mycobacterium tuberculosis (tuberculosis), and yellow fever virus (yellow fever) from Jan 1, 1974, to Dec 31, 2024, across 194 WHO member states. We compared costs (procurement, administration, and family additional costs from time spent synthesised from authoritative global databases and systematic literature reviews) and benefits (primarily averted mortality retrieved from published global burden estimates) between observed EPI implementation and a counterfactual scenario of no vaccination, from which BCRs and ICERs were derived. From 1974 to 2024, the cost of EPI reached US$937 billion (95% CI 699-1187), offset by $15 050 billion (12 609-17 605) in averted productivity losses due to mortality (aggregate BCR 16·06 [95% CI 10·62-25·20]; ICER cost-saving). Immunisation against all 14 pathogens showed favourable economic outcomes. Measles vaccination produced the highest BCR (73·97 [45·78-124·06]), and the ICERs for all vaccines remained below conventional cost-effectiveness thresholds. EPI against 14 pathogens in aggregate achieved cost savings (BCR>1) in all 194 WHO member states. Economic returns varied across six WHO regions and four World Bank income groups, with the Eastern Mediterranean region (BCR 17·22 [11·22-28·67]) and low-income countries (BCR 23·63 [16·87-34·32]) showing the highest BCRs. The 50-year EPI has proven highly cost-effective at global, regional, and national levels, and remains a worthwhile investment. The EPI delivered impactful life-saving benefits and favourable economic returns, especially in high-burden and low-income settings. The National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Vaccine Impact Modelling Consortium, and the Japan Agency for Medical Research and Development.
National governments and multilateral institutions face difficult challenges reconciling biodiversity, climate, and economic development goals. We integrated spatial biophysical and economic data with optimization methods to develop sustainable landscape efficiency frontiers that show maximally feasible combinations of biodiversity conservation, land-based climate mitigation, and net economic value from agricultural crops, livestock, and forestry production. We applied this approach in 146 countries and found large potential gains in biodiversity, climate, and economic development from improved land use and land management. Summing national-level results shows the potential to increase climate mitigation by more than 200 billion metric tons of CO2 equivalents (>20% increase) or net economic value by more than US$350 billion (>80% increase), without loss in other objectives.
Since COVID-19 vaccine introduction in December 2020, > 13 billion doses have been distributed globally, including > 5 billion Pfizer-BioNTech (BNT162b2) doses. Real-world evidence in pregnancy remains heterogenous in design and outcome definitions, with limited analysis by dose timing or variant period. Most reviews evaluated COVID-19 vaccines as a class without focus on individual products, limiting product-specific interpretation. Given expanding evidence and public concern around safety of vaccines during pregnancy, an updated, pregnancy-focused systematic review of BNT162b2 safety is warranted. This study aimed to review and synthesize evidence on the safety of Pfizer-BioNTech COVID-19 vaccine in pregnant women, including pregnancy-related outcomes. A systematic literature review (PROSPERO registered) was conducted in accordance with Cochrane methodology and reported following PRISMA guidelines. Medline and Embase were searched from December 2020 to June 2025, supplemented by regulatory reports and conference searches. Eligible randomized and observational studies reporting obstetric or neonatal outcomes after ≥ 1 dose of BNT162b2 were included. Quality appraisal was conducted using NICE checklists. Results were narratively synthesized and reported following SWiM guidance. Across 25 studies, comprising > 450,000 BNT162b2-vaccinated pregnant women, no increased risk was observed for miscarriage, congenital anomalies, preterm birth, hypertensive disorders, small for gestational age, low birth weight, or neonatal death, with effect estimates broadly consistent and centered around the null across available trimester-stratified analyses, dose numbers, and study design. However, trimester-specific data, particularly for first-trimester exposure, were limited. The cumulative evidence demonstrates a reassuring safety profile for Pfizer-BioNTech (BNT162b2) COVID-19 vaccination with no indication of increased pregnancy-related or neonatal risk. The evidence is mainly observational and heterogeneous, with limited precision for rare outcomes, but the results align with findings from international registry, surveillance, and population-based evidence and support BNT162b2 vaccination in pregnancy as an effective and safe means to reduce preventable maternal morbidity, although evidence remains limited for first-trimester-specific exposure. The review protocol was prospectively registered with PROSPERO [CRD420251080193] [1].
Surface-enhanced Raman spectroscopy (SERS) is rapidly emerging as a transformative technology in dermatological diagnostics, offering ultra-sensitive, noninvasive detection of molecular markers associated with skin diseases. With nearly five billion individuals affected worldwide and conventional diagnostic methods often limited by invasiveness or subjective interpretation, there is an urgent need for rapid, accessible, and real-time diagnostic solutions. The present review systematically examines the integration of SERS into dermatological practice, with a focus on recent advancements in biosensing platforms, nanostructure engineering, and point-of-care devices. Innovative methodologies, including microneedle-based SERS biosensors and microfluidic-integrated detection systems, are discussed in the context of their ability to enhance diagnostic accuracy for early-stage skin cancers, microbial infections, and inflammatory dermatoses. Furthermore, the review highlighted the role of AI-driven spectral analysis in improving data interpretability and clinical decision-making. Critical evaluation of the challenges of substrate reproducibility, clinical standardization, and device scalability, while outlining emerging strategies that aim to bridge laboratory innovations with clinical applications, are explored. Looking ahead, the development of portable, low-cost SERS platforms for continuous skin health monitoring, combined with personalized diagnostic pathways, is poised to redefine dermatological care and expand the scope of precision medicine. Skin diseases impact 4.8 billion people globally, imposing substantial mortality and economic burdens, highlighting the urgent need for accurate, timely diagnostics. Current approaches are often invasive, time-intensive, or lack sensitivity. The present review critically examines the transformative potential of surface-enhanced Raman spectroscopy (SERS) as a minimally invasive, point-of-care solution for dermatological diseases and effective care management. The primary focus of this review is to explore the potential use of SERS in dermatological diagnostics, an area where traditional Raman spectroscopy has seen limited application. Integrating advanced spectroscopic techniques, lab-on-a-chip platforms and opto-microfluidic systems, it explores progressive SERS capabilities for early detection and disease management. By bridging medical engineering, medicine and biochemistry, this work addresses a critical knowledge gap, fostering interdisciplinary innovation to advance dermatological diagnostics and improve global health outcomes.
Globally, approximately 3.5 billion people lack safely managed sanitation services. In Africa, 45% of the population uses either shared or unimproved sanitation facilities. Ethiopia continues to be ranked among the countries with the lowest levels of hygiene and sanitation coverage. Moreover, many villages and kebeles who have latrine practicing open defecation. So the objective of this study is to assess sustainable latrine utilization and associated factors among open defecation free (ODF) declared villages in Ebinat District. A community based cross-sectional study triangulated with qualitative data was conducted from January 17 to February 11/2017 in Ebinat District. Multistage sampling was employed to select study subjects. A total of 752 households were selected by using systematic random sampling technique. Four focus group discussion and seven key informant interview participants were selected purposively to collect qualitative data. The Data entered using Epi Info version 7 and exported to SPSS version 20 for analysis. Crude and adjusted odds ratio with 95% CI were computed to identify the predictors of sustainable latrine utilization. Open Code software was used for thematic content analysis. The overall sustainable latrine utilization was 31.5 % with 95% CI of (28.2, 34.8). Factors associated by households were presence of children 7-18 years old, attending elementary school [AOR:1.63, 95% CI: (1.09-2.45)], HHs ever visited in a year by health extension workers [AOR:3.15, 95% CI: (1.80-5.53)], HHs ever visited in a year by health development armies [AOR:3.23, 95% CI: (1.99-5.26)] and family member attending Community-Lead Total Sanitation and Hygiene triggering [AOR:1.78, 95% CI: (1.16-2.67)] and distance of latrine from dwelling [AOR:3.22, 95% CI: (1.54-6.72)]. In this study, sustainable latrine utilization is lower than expected level. Therefore, program implementers should prioritize behavioral change interventions, and health workers and HDAs should conduct frequent follow-ups after the ODF declaration. Globally, 2.4 billion people do not have access to improved sanitation facilities. In African, 45% of the population uses either shared or unimproved sanitation facilities. Ethiopia continues to be ranked among the countries with the lowest levels of hygiene and sanitation coverage. So the objective of this study is to assess sustainable latrine utilization and associated factors among open defecation free (ODF) declared villages in Ebinat District, Northwest Ethiopia. A community based cross-sectional study triangulated with qualitative data was conducted from January 17 to February 11/2017 in Ebinat District. A total of 752 households (HHs) were selected by using multistage sampling technique. Four focus group discussion and in-depth interview participants were selected purposively to collect qualitative data. Data were collected using structured questionnaire and observational checklist. The Data entered using Epi Info version 7 and exported to SPSS version 20 for analysis. Crude and adjusted odds ratio with 95% CI were computed to identify the predictors of sustainable latrine utilization. Open Code software was used for thematic content analysis. The overall sustainable latrine utilization was 31.5 % with 95% CI of (28.2, 34.8). Factors associated by households were presence of children 7-18 years old, attending elementary school [AOR:1.63, 95% CI: (1.09-2.45)], HHs ever visited in a year by health extension workers [AOR:3.15, 95% CI: (1.80-5.53)], HHs ever visited in a year by health development armies (HDAs)[AOR:3.23, 95% CI: (1.99-5.26)] and family member attending community lead total sanitation and hygiene (CLTSH) triggering [AOR:1.78, 95% CI: (1.16-2.67)] and distance of latrine from dwelling [AOR:3.22, 95% CI: (1.54-6.72)]. In this study, sustainable latrine utilization is lower than expected level. Therefore, program implementers should prioritize behavioral change interventions.
The exponential growth of accessible chemical space represents a significant computational challenge for structure-based virtual screening. Hence, active-learning and machine-learning approaches, such as Deep Docking, have been introduced to significantly speed up this process; yet even such methods became computationally prohibitive as docking libraries expanded into and beyond billion-entries levels. To address this challenge, we herein introduce the Deep Docking Ultra (DDU) approach, which integrates advanced acquisition functions with a pre-trained molecular large language model (MLLM). We demonstrate that such a combination improves accuracy of docking score emulations, while significantly reducing their computational costs. Through 384 virtual screening experiments involving 12 proteins from all major target classes, we systematically benchmarked DDU performance to identify optimal configurations that reduce required computations by up to 45-fold compared to the original Deep Docking method, and by up to 28 500-fold, compared to brute-force docking, without compromising predictive accuracy. We further demonstrate that DDU is able to screen 10.1 billion ligands against the phosphoglycerate kinase 2 target in just 10 days using 50 tesla V100 GPUs, and yields an overall docking enrichment factor of 12 000.
Antimicrobial resistance is driven by inappropriate antibiotic use, and Türkiye has long shown one of the highest outpatient consumption rates in the WHO European Region. In response, the Ministry of Health implemented stewardship measures from 2014 onward, including the National Action Plan for Rational Drug Use, banning over-the-counter antibiotic sales, integrating e-prescribing with mandatory diagnostic coding, educational initiatives, and audit-feedback systems. This study evaluated temporal trends in primary care antibiotic prescribing in Türkiye between 2011 and 2019 and assessed the influence of these interventions. We performed a nationwide descriptive analysis using aggregated Prescription Information System (RBS) data covering all family-physician prescriptions (2011-2019). Outcomes included: (i) proportion of prescriptions containing systemic antibiotics (ATC J01), (ii) consumption in DID, (iii) use by ATC-3 class and AWaRe category, (iv) antibiotic share of drug volume and cost, and (v) patterns by age, sex, and diagnosis. Trends were summarized using annual percentages and DID values. The two pre-specified primary outcomes were the annual antibiotic prescription rate and total systemic antibiotic consumption (DID, ATC J01); other indicators were treated as secondary. Because the RBS captures only e-prescribed antibiotics, over-the-counter sales (legal in Türkiye until 2016) are not included. Segmented (interrupted time-series) regression with Newey-West HAC standard errors was applied to test for changes in level and slope at 2016, when prescription-only dispensing was fully enforced and mandatory ICD-10 coding was consolidated within the e-prescribing system. Among 1.17 billion prescriptions, the share containing an antibiotic declined from 34.9 to 23.9%, while consumption fell from 42.3 to 31.9 DID (-25%). Beta-lactams showed the largest reductions, though Watch-group agents still formed nearly half of use in 2019, below the WHO ≥60% Access target. Pediatric prescribing decreased most: use in children aged 0-6 years dropped from 60 to 44% of visits. Elderly patients had the lowest rates. Diagnostic coding shifted away from nonspecific upper-respiratory infections. Antibiotics' share of outpatient drug costs fell from 10.7 to 4.7%, yielding an estimated 1.7 billion TL savings in 2018. Segmented regression confirmed an acceleration of the decline after 2016: the slope changed by -0.69 percentage points/year for the prescription rate (95% CI - 1.44 to +0.06; p = 0.07) and by -0.80 DID/year for total consumption (95% CI - 0.88 to -0.72; p < 0.001) versus the pre-2016 trajectory. Türkiye achieved major reductions in primary care antibiotic use within a decade, temporally concordant with multifaceted stewardship policies whose individual contributions cannot be isolated by this descriptive design. However, outpatient levels remain above many EU countries, and Watch-group use is still high. Further progress requires stronger guideline adherence, prioritization of Access antibiotics, and wider use of point-of-care diagnostics.
Prostate cancer (PCa) is the second most common cancer worldwide and the sixth leading cause of cancer deaths in men. In South Africa (SA), PCa accounts for ~13% of male deaths. The direct medical costs associated with PCa diagnosis and treatment according to the national clinical guidelines for prostate cancer control and management are not documented. To estimate the direct medical costs for localised PCa diagnosis and treatment according to the national clinical guidelines for prostate cancer control and management in SA. The direct medical costs for diagnosis and treatment of prostate cancer were estimated from the payer's perspective using a micro- costing approach, with a time horizon of 12 months. Cost items were identified from the national PCa clinical guidelines and quantified according to the treatment options for low- (LRPCa), intermediate- (IRPCa) and high-risk (HRPCa) categories. Cost data were obtained from different government databases. The unit costs and PCa incidence data from 2022 were then used to estimate total costs for treating all new PCa cases. Total costs were calculated for each treatment method listed in the clinical guidelines according to PCa risk categories. The total cost for treating 10 944 new PCa cases in 2022 was estimated at ZAR2.1 billion. Per patient costs ranged from ZAR7 265 to ZAR143 156 for LRPCa, ZAR8 926 to ZAR144 817 for IRPCa and ZAR14 874 to ZAR151 872 for HRPCa. The total cost for managing all patients with LRPCa, IRPCa and HRPCa were estimated at ZAR401.3 million, ZAR371.1 million and ZAR1.4 billion, respectively. This study estimated the cost for diagnosis and treatment of localised PCa according to national clinical guidelines for PCa control and management. The costs increased with each risk category of the cancer. The study highlights the need for policy-makers to increase early detection and management, to reduce the need for high-cost interventions.
This study aims to evaluate the health burden and macroeconomic impact of type 2 diabetes mellitus (T2DM) attributable to high body mass index (BMI) in Southeast Asia. We analysed trends with Joinpoint regression and assessed health inequalities using slope and concentration index. We projected future burden with a Bayesian Age-Period-Cohort model. We then applied the Productivity-Adjusted Life Years framework to quantify productivity losses from deaths and disability, valuing the economic impact with projected GDP per capita. The burden of high BMI-attributable T2DM increased significantly from 1990 to 2023 and is projected to continue rising. This translates into substantial productivity losses, with total PALYs lost projected to increase from 1.86 million in 2024 to 2.03 million in 2029. The corresponding economic losses were projected to rise from Intl$29.94 billion to Intl$38.44 billion. Males and the 50-64 age group bore a disproportionate burden, with Indonesia bearing the largest absolute economic impact. High BMI-related T2DM causes a major and growing health and economic burden in Southeast Asia. Policymakers must urgently act to reduce obesity and limit its economic effects.
Obstructive sleep apnea (OSA) is a major public health crisis affecting nearly one billion people worldwide and is associated with significant cardiovascular and metabolic complications. The prevalence of OSA is rising steadily due to the obesity pandemic and is contributed by interacting anatomical, inflammatory, and neuro-respiratory mechanisms. Continuous positive airway pressure (CPAP) remains the gold standard for the management of OSA; however, it does not address underlying obesity or weight-independent pathophysiology. Obesity is an important modifiable risk factor for OSA, as weight loss is associated with resolution/improvement of the disease. Therefore, growing evidence now supports surgical and medical management of obesity as complementary strategies to improve both body weight and apnea-hypopnoea index (AHI), prompting a paradigm shift towards integrated, multimodal care. Bariatric interventions typically achieve 25%-35% total weight loss and yield significant but variable reductions in AHI with remission rates of 50%-75%, driven by mechanical unloading, improved ventilatory control, and favorable metabolic and anti-inflammatory effects. However, it is constrained by eligibility, cost, and perioperative risks. Alternatively, Incretin-based therapies, particularly Tirzepatide, achieve 10%-22% weight loss and reduce AHI to 12-30 events per hour, securing the first regulatory approval for OSA based on the largest trial-level AHI reductions. The recent introduction of several therapeutic agents with excellent weight loss potential has reshaped the management landscape of people with obesity and OSA. This review aims to analyze the literature across surgical, endoscopic, and pharmacological interventions and OSA while proposing an individualized treatment framework integrating weight-loss pharmacotherapy with device-based and structured lifestyle strategies and surgical interventions, tailored to disease phenotypes.
The European corn borer, Ostrinia nubilalis (Hübner), is an economically important pest of corn that historically caused over $1 billion annually in yield losses and control costs. Since 1996, widespread adoption of transgenic corn producing Bacillus thuringiensis (Bt) proteins has substantially suppressed O. nubilalis populations in the US Corn Belt. However, recent cases of practical resistance reported in Nova Scotia (Canada) and Connecticut (US) between 2018 and 2023 threaten the long-term benefits of Bt corn technology. Here, we used F2 screens and diet-overlay bioassays to estimate resistance allele frequency to the Cry2Ab2 Bt protein in O. nubilalis populations collected from multiple locations across Minnesota and Wisconsin during 2023 and 2024. We established a total of 84 F2 families by crossing field-collected insects with a susceptible laboratory strain and screened 7,466 neonates against Cry2Ab2 protein. We found that 21 of the 84 F2 families carried at least 23 major resistance alleles to Cry2Ab2, with an estimated resistance allele frequency of at least 0.1509 in the region. This value exceeds the <0.001 ideal resistance allele frequency for the pyramiding strategy by >150.9-fold. The high Cry2Ab2 resistance allele frequency observed in O. nubilalis may compromise the redundant killing underlying pyramided Bt technology, resulting in pyramided Bt corn functioning as single-trait Bt hybrids against O. nubilalis and potentially accelerating resistance evolution in the field. The data generated in this study provides critical information on current resistance risk in O. nubilalis and will help develop sustainable insect resistance management (IRM) strategies for this pest.
The alternative splicing landscape of cancer transcriptomes remains poorly characterized, since short read sequencing cannot resolve complete transcript structures. Using the Oxford Nanopore cDNA platform, we generated nearly 2 billion long reads (median 25.8 million per sample) from 71 human samples, including 48 acute myeloid leukemia or myelodysplastic syndrome samples, 25 of which had splicing-factor gene mutations (in SRSF2 , U2AF1 , or SF3B1 ). An additional 23 samples were from sorted hematopoietic cell populations from healthy individuals. We identified 174,162 novel isoforms absent from the reference transcriptome, and proteomic validation confirmed that many are translated. We also identified isoforms enriched in spliceosome-mutant samples, and found proteomic evidence of frequent nonsense-mediated decay regulation of novel transcripts. This dataset is a valuable community resource, enabling detection of new transcripts in short read data sets. An interactive portal to explore splicing patterns in these data is available at https://leylab.org/isoforms/ .
The U.S. Department of Veterans Affairs (VA) has invested billions of dollars to address homelessness, but there has been limited analysis of long-term outcomes. This retrospective study followed 2 cohorts of homeless veterans over 2 decades to identify long-term trajectories and predictors of mortality and continued VA homeless program use. National VA administrative data were analyzed from 2004 to 2024. A 2004 cohort of 85,533 homeless veterans and a 2014 cohort of 222,974 homeless veterans. Primary outcomes were mortality and continued use of VA homeless programs. A total of 50% of the first cohort died within 20 years (mean=63.9 y old) and about one-quarter of the second cohort died within 10 years (mean=65.3 y old). Of surviving veterans, 25% in both cohorts used VA homeless programs, and 32%-36% used VA emergency department/urgent care in 2024. In both cohorts, predictors of mortality included being older, non-Hispanic White, male, having medical comorbidities, and alcohol use disorder. Predictors of continued use of VA homeless programs included non-Hispanic Black, male, unmarried, low-enrollment priority group, military sexual trauma, and drug use disorder. In both cohorts, 61%-81% with substance use disorders received substance use treatment, but generally of short duration. In a homeless population with access to comprehensive health care, there is a long-term need to address premature mortality, substance use disorders, and pathways to independence. These findings signal the work that remains in the VA, and the broader challenges that may lie ahead in other national efforts to address homelessness.
Friedreich's ataxia (FA) is marked by early-onset sensory neurodegeneration and cardiomyopathy. We establish a human dual-cell model of FA by differentiating sensory neurons and cardiomyocytes from the same patients, enabling parallel molecular profiling of disease-relevant cell types. Proteomic analysis reveals distinct, cell-type-specific pathway disruptions in response to frataxin deficiency. Leveraging this platform, we investigate Miro1 reducer 3 (MR3), a selective chemical probe binding Miro1, a mitochondrial outer membrane protein implicated in redox regulation in FA. MR3 treatment modulates molecular signatures in a cell-type-dependent manner, altering pathways related to cardiac contractility in cardiomyocytes and synaptic function in sensory neurons. Mechanistically, MR3 reduces mitochondrial reactive oxygen species and restores membrane potential in FA sensory neurons via potential allosteric reshaping of Miro1 protein. We expand the chemical diversity of this scaffold by conducting ligand-based virtual screening of over 3 billion compounds and identifying previously uncharacterized Miro1 ligands with improved docking and neuroprotective capacity.