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For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Gates Foundation and Bloomberg Philanthropies.

Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time. We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution. In 2023, 60·1 million (95% UI 59·0-61·1) deaths occurred globally, of which 4·67 million (4·59-4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2-38·4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8-67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6-51·7) years for females and 47·9 (47·4-48·4) years for males in 1950 to 76·3 (76·2-76·4) years for females and 71·4 (71·3-71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6-74·8) years for females and 69·3 (69·2-69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0-76·6] years for females and 71·5 [71·2-71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally. This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world. Gates Foundation.

Saudi Arabia ranks seventh in the world for diabetes prevalence, yet many individuals are unaware of the disease. Increasing awareness, particularly among future health professionals who are often consulted for guidance, is essential to reduce the burden of diabetes. It is needed; to what extent do preprofessional health sciences students in Saudi Arabia understand type 2 diabetes mellitus (T2DM), including prevention, screening, and treatment? This study aimed to assess the knowledge and awareness of T2DM among preprofessional health sciences students in Saudi Arabia, with a focus on prevention, screening, and treatment. A descriptive cross-sectional study was conducted among 429 health professions students (required sample size: 317). The questionnaire included demographic data followed by 47 questions assessing knowledge of diabetes. Descriptive statistics were used to summarize demographic characteristics, while logistic regression with the forward-backward with early dropping variable selection algorithm (R package MXM) was applied to analyze the influence of demographic factors on knowledge scores. Out of the 429 participants, 63.6% were male and 36.4% were females. The majority (92.1%) were aged 20 years or younger, with 60.1% being first-year students. A notable percentage (78.1%) reported having diabetic relatives. Most participants (96.3%) recognized that diabetes is preventable; however, 86.7% mistakenly thought that prediabetes is irreversible. While over 90% exhibited good understanding of the symptoms and risk factors of diabetes, 63.6% were unaware of the role of oral hypoglycemic agents in treatment. Conversely, knowledge regarding the use of insulin e was well comprehended by 93.0% of the respondents. The study suggests that health professional students in Saudi Arabia have a good understanding of type 2 diabetes; however, they exhibit a deficiency in knowledge about the use of oral hypoglycemic agents and the potential for reversing prediabetes. By addressing these gaps through curricular enhancements, future health care professionals could be better prepared to confront the escalating diabetes epidemic in the region.

Acute psychotic symptoms like delusions and hallucinations are of major concern while treating patients with schizophrenia and alzheimer's psychosis, primarily impacting their daily life functioning and quality of life. The traditional antipsychotic medications, commonly prescribed to manage these symptoms, cause significant side effects with limited efficacy, requiring novel therapeutic agents that can overcome this challenge. While there is no definitive cure, symptomatic treatment can help relieve some of the symptoms and improve the quality of life of people with alzheimer's disease (AD). A comprehensive literature search of PubMed, scopus, google scholar, and ClinicalTrials.gov was conducted to identify studies on xanomeline-trospium chloride (KarXT) in schizophrenia and AD psychosis. After screening 802 unique records, 39 studies-including preclinical, clinical, and observational investigations-were included in this narrative review. Only English-language publications up to February 2025 were considered. KarXT, with its dual action on the M1 and M4 receptors and mAChR antagonism, greatly helps reduce the severity of the positive and negative symptoms, as it resulted in an 8.4-point greater reduction on the PANSS scale. Side effects were minimal and did not account for the discontinuation of treatment. Psychosis is a common feature of schizophrenia and AD, most often caused by high concentrations of dopamine in the brain, characterized by hallucinations, delusions, and disorganized thinking, resulting in markedly reduced quality of life for the patient and associated caregiver. Conventional treatments targeting dopamine receptors produce extrapyramidal symptoms and metabolic side effects, leading to noncompliance with medication. KarXT, with its dual action on M1 and M4 receptors and mAChR antagonism, greatly helps reduce the severity of the positive and negative symptoms. The side effects experienced were minimal and did not account for the discontinuation of treatment.An overview of the mechanism of action, clinical trials, and classical findings of KarXT for the management of psychotic symptoms in patients with schizophrenia and alzheimer's disease.

Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

Acute poisoning is a significant public health concern, leading to numerous emergency admissions globally. In northwestern Syria, understanding poisoning epidemiology is essential for targeted prevention efforts. This study examines the causes and demographic characteristics of poisoning cases in the region. The study was conducted over 1 year (July 1, 2022-July 1, 2023) at six northwestern Syrian hospitals supported by humanitarian organizations. The study gathered information from patients aged 14 years and above who suffered from poisoning during the study period. Poisoning cases totaled 172 throughout the study period. Majority of patients were females aged between 14 and 24 (76.7 and 55.2%, respectively), most of them were married (65.1%). Most of the patients identified as housewives among the total patient population (52.9%) and had primary or middle school education. A large majority of the population (77.3%) were smokers while most poisoning incidents (77.3%) were reported in rural camps and villages. The study found oral ingestion as the most common route of poisoning at 88.4% and intentional poisonings made up 86% of all cases. The most prevalent toxic agents causing poisoning cases were drugs, 61.6%, with organophosphorus compounds ranking second, 14.5%. The symptom of vomiting appeared most often during acute poisoning cases (48.8%). The administration of specific antidotes took place in 11.6% of patients who needed hospital admission for 94.8% of these cases. The patients stayed in the hospital for an average duration of 33.1 hours. A total of 76.7% of patients achieved full recovery and 7.6% succumbed to their injuries. Acute poisoning presents as a major health problem across northwestern Syria mostly affecting young married females who live in rural regions. The unusually high number of cases of purposeful poisoning emphasizes the requirement for both psychiatric support and educational programs for the public.

BACKGROUND: Parkinson&#x2019;s disease (PD) is the second most common neurodegenerative disorder worldwide, characterized by the loss of dopaminergic neurons in the substantia nigra. Recent studies suggest that immune dysregulation and alterations in signaling pathways play a key role in PD pathogenesis. The aim of this study was to investigate the expression of Signal transducer and activator of transcription (STAT) and Suppressor of cytokine signaling (SOCS) family genes in PD patients compared to control group. METHODS: Expression of STAT and SOCS family genes in peripheral blood cells were measured using RT-qPCR technique and the results were statistically analyzed using R software. RESULTS: There was no significant difference in the expression of STAT1, STAT3, STAT4, and STAT6 genes between the patient and control groups. However, the expression of SOCS1, SOCS2, SOCS3, SOCS5, and STAT5a genes in patients showed a significant decrease compared to the control group (p&#x2009;<&#x2009;0.001, =&#x2009;0.003, =&#x2009;0.004, =&#x2009;0.03 and =&#x2009;0.007 respectively). Such decreases were significant between male subgroups for all these genes except SOCS5, for which neither male nor female subgroups showed a statistically significant difference. Regarding age, the expression of STAT1 and STAT6 genes decreased with increasing age (p&#x2009;=&#x2009;0.046 and 0.04 respectively), while the decrease in STAT5a expression with increasing age was only seen in females (p&#x2009;=&#x2009;0.001). CONCLUSION: Our study demonstrated that the expression of STAT5a, SOCS1, SOCS2, SOCS3, and SOCS5 genes was significantly reduced in PD. Given that these molecules play a crucial role in anti-inflammatory pathways, their reduced expression may indicate defect in these pathways that contribute to the pathogenesis of PD. However, further studies are required to elucidate the exact effects of these changes.

Middle Eastern Americans represent a growing and understudied population in cancer genomics. While lung cancer driver mutations are well characterized in many populations, data remain limited for individuals of Middle Eastern ancestry living in the United States. Smoking histories were observed, but available evidence in this population is sparse. We conducted a retrospective, descriptive analysis of lung carcinoma specimens from 31 Middle Eastern American patients who underwent next-generation sequencing (NGS). Mutations in KRAS, EGFR, ALK, BRAF, and MET were identified using targeted NGS panels. Smoking exposure and duration of U.S. residence were summarized descriptively. Mutation frequencies were compared with published datasets from Middle Eastern populations, including My Cancer Genome and the American University of Beirut Medical Center. NGS using the formalin-fixed paraffin-embedded block was performed using the TruSight Oncology 500 Kit or the TruSight Tumor 15 Kit (Illumina, San Diego, California, United States). Data analysis was performed by aligning to human genome assembly GRCh37 (hg19). A custom variant filter was set up to include only nonsynonymous variants with coding consequences and read depth greater than 100X. Variants classified as IA or IB in ALK, BRAF, EGFR, KRAS, and MET were compared in this study. Benign variants, based on the ClinVar database, were excluded. Given the limited sample size, analyses were descriptive in nature. Continuous variables are presented as means, and categorical variables as counts and percentages. No inferential statistical testing was performed due to insufficient statistical power to reliably detect associations between smoking history and mutation status. The study is intended to be hypothesis-generating. KRAS mutations were the most frequently observed (38.7%), followed by EGFR (19.4%) and ALK (9.7%). EGFR mutations occurred predominantly in individuals with minimal smoking exposure, whereas KRAS mutations were more common among individuals with higher pack-year histories. BRAF and MET mutations were rare. Due to limited sample size, no inferential statistical testing was performed, and findings should be interpreted as exploratory. This descriptive study characterizes lung cancer driver mutations in Middle Eastern Americans and identifies patterns consistent with known smoking-associated and non-smoking-associated mutation profiles. While limited by sample size, the findings emphasize the importance of including Middle Eastern Americans in cancer genomic research and larger, statistically powered studies incorporating additional smoking history and ancestry data are needed to clarify these associations and their clinical implications. KRAS mutations were the most common mutations in our study, occurring in 38.71% of cases, with an average of 10.42 years of residence in the United States and 27.3 pack-years of smoking exposure. EGFR mutations are found in 19.35% of cases, with relatively low smoking exposure (1.25 pack-year). Both MET and BRAF mutations are rare, each accounting for 3.23% of the cases. BRAF mutations were detected in patients with the highest smoking exposure (70 pack-years); however, it should be noted that this value is elevated due to only having one positive case in this study. ALK mutations account for 9.68% of cases. On average, the study population spent 8.58 years of residency in the United States and 22.67 pack-years of smoking exposure, demonstrating a range of smoking histories and mutation frequencies. These findings were compared with data from My Cancer Genome, the American University of Beirut Medical Center, and specific EGFR mutation rates in the Middle Eastern population. Understanding these dynamics is essential for developing targeted public health strategies that address the unique challenges faced by this population, balancing their cultural heritage with the realities of modern American life. Further analysis and wider scope studies are necessary to explore the implications of these findings on health outcomes.

Renal colic is a common urological emergency that requires a noncontrast computed tomography of the kidneys, ureters, and bladder (CT KUB) as the investigation of choice. This two-cycle audit was conducted at Manchester Royal Infirmary; a tertiary hospital in the United Kingdom. It evaluates the appropriateness of CT KUB imaging for acute renal colic, focusing on scan timing, diagnostic yield, and request adequacy in line with national guidelines. We performed a retrospective review of patients referred from the accident and emergency department for suspected renal colic. The first cycle was conducted in September to October 2022 and the second in August 2023. The intervention included disseminating the findings and designing an educational program. Statistical analysis was performed using SPSS version 30.0. Continuous variables were compared using independent t -tests, and categorical variables using chi-square tests. A p -value of&#x2009;<&#x2009;0.05 was considered statistically significant. A total of 153 patients were included (first cycle: 77; second cycle: 76). Following the intervention, the mean time from presentation to CT KUB report decreased significantly from 14.7&#x2009;&#xb1;&#x2009;9.5 to 8.2&#x2009;&#xb1;&#x2009;5.1&#x2009;hours ( p &#x2009;<&#x2009;0.001). The proportion of scans reported within 24&#x2009;hours also increased from 92.2 to 100% ( p &#x2009;=&#x2009;0.007). Documentation of a sufficient history improved from 76.6 to 89.5% ( p &#x2009;=&#x2009;0.034). Additionally, reports of nonspecific abdominal pain decreased from 9.1 to 0% ( p &#x2009;=&#x2009;0.007). Targeted educational interventions improved CT KUB timeliness, request quality, and adherence to national guidelines. These results confirm the value of structured clinical pathways and cross-departmental collaboration in optimizing the investigation of suspected renal colic.

To systematically evaluate the quality, accessibility and patient-centred performance of primary healthcare services in Kazakhstan and to generate pooled quantitative estimates of key patient-centred and system-level outcomes, with specific attention to their implications for primary healthcare nursing practice, nurse-led quality improvement and nursing policy. Systematic review and meta-analysis conducted in accordance with PRISMA guidelines. Scopus, Web of Science and PubMed were systematically searched for eligible studies published between January 2015 and December 2025. Observational, cross-sectional, mixed-methods and interventional studies assessing PHC quality domains in Kazakhstan were included. Two reviewers independently screened studies, extracted data and assessed methodological quality using the Joanna Briggs Institute (JBI) appraisal tools for observational studies and the Cochrane RoB 2 tool for the cluster-randomized trial. Random-effects meta-analyses were conducted for (1) patient-centred outcomes and (2) system-level PHC performance indicators. Statistical heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using funnel plots. Eight studies met the inclusion criteria and were included in the qualitative synthesis and meta-analysis. Four studies contributed data on patient-centred outcomes, yielding a pooled patient satisfaction proportion of 0.56 (95% CI: 0.53-0.59; I2&#x2009;=&#x2009;48.7%). Four studies reported system-level performance indicators, with a pooled estimate of 0.64 (95% CI: 0.52-0.75; I2&#x2009;=&#x2009;98.4%). Funnel plots were used for descriptive purposes only and were interpreted cautiously, as each meta-analysis included only four studies, making reliable assessment of publication bias not feasible. This systematic review and meta-analysis provides the first consolidated quantitative assessment of PHC quality in Kazakhstan. While patient satisfaction and system-level performance appear moderate, substantial heterogeneity and regional disparities remain. Strengthening PHC quality will require standardized performance indicators, enhanced digital health integration and targeted interventions to reduce urban-rural inequalities. The findings of this study have important implications for clinical nursing practice and healthcare management. Given the central role of primary healthcare nurses in patient communication, care coordination, chronic disease monitoring, and preventive services, the identified gaps in patient satisfaction and system-level performance highlight key areas for nursing-led improvement. Enhancing nurse involvement in patient education, continuity of care, and service accessibility may contribute to improved patient experiences and health outcomes. These findings support the need for strengthening nursing capacity, expanding nurse-led models of care and integrating nursing perspectives into PHC quality improvement strategies within Kazakhstan's evolving healthcare system. Not applicable.

Multiple-choice questions (MCQs) are vital tools for assessment in education because they allow for the direct measurement of various knowledge, skills, and competencies across a wide range of disciplines. While artificial intelligence (AI) holds promise as a supplementary tool in medical education, particularly for generating large volumes of practice questions, it cannot yet replace the nuanced and expert-driven process of question creation that human educators provide. This study seeks to close the gap, particularly with regard to difficulty index, discrimination index, and distractor efficiency. A total of 50 medical students received a set of fifty randomized, blinded, validated MCQs by human physiology experts. Of these, 25 were made by AI, and the remaining 25 were made by qualified, experienced professors. Using the item response theory (IRT) framework, we calculated key metrics like item reliability, difficulty index, discrimination index, and distractor functionality. The results demonstrated that the difficulty index of AI-generated MCQs (mean&#x2009;=&#x2009;0.62, SD&#x2009;=&#x2009;0.14) was comparable to that of expert-generated questions, with no statistically significant difference observed ( p &#x2009;=&#x2009;0.45). However, significant differences emerged in other key quality metrics. The discrimination index, which reflects a question's ability to distinguish between high- and low-performing students, was notably higher for expert-created MCQs (Mean&#x2009;=&#x2009;0.48, SD&#x2009;=&#x2009;0.12) than for those generated by AI (Mean&#x2009;=&#x2009;0.32, SD&#x2009;=&#x2009;0.10), indicating a moderate-to-large effect (p&#x2009;=&#x2009;0.0082, Chi-square&#x2009;=&#x2009;11.7, df&#x2009;=&#x2009;3). Similarly, distractor efficiency (DE), which evaluates the effectiveness of incorrect answer options, was significantly greater in expert-authored questions (Mean&#x2009;=&#x2009;0.24, SD&#x2009;=&#x2009;7.2) compared to AI-generated items (Mean&#x2009;=&#x2009;0.4, SD&#x2009;=&#x2009;8.1), with a moderate effect size (p&#x2009;=&#x2009;0.0001, Chi-square&#x2009;=&#x2009;26.2, df&#x2009;=&#x2009;2). These findings suggest that while AI can replicate human-level difficulty, expert involvement remains crucial for ensuring high-quality discrimination and distractor performance in MCQ design. The findings suggest that AI holds promise, particularly in generating questions of appropriate difficulty, but human expertise remains essential in crafting high-quality assessments that effectively differentiate between levels of student performance and challenge students' critical thinking. As AI technology continues to evolve, ongoing research and careful implementation will be essential in ensuring that AI contributes positively to medical education.

Introduction &#x2003;Case reports and series are critical to guide initial decision-making in a pandemic, but may have lower rigor because of the need to publish them quickly. This meta-epidemiologic study compares the methodological quality of case series that described the acute coronavirus disease 2019 (COVID-19) pandemic in 2020 versus those that described long-haul cases. Methods &#x2003;We conducted a systematic review in multiple databases for long-haul case series and reports. We identified early cases of acute COVID-19 synthesized in published systematic reviews. We evaluated the methodological quality by pairs of independent reviewers using a tool dedicated for appraising case series. Results &#x2003;We included 239 original case series (81 published in the first year of the pandemic and 158 published later describing long-haul COVID). The methodological quality of both groups of case series was very good (80-100% of series satisfying quality items) except for two items, the selection approach of cases included in the series and ruling out other causes that can explain the main finding described in the series. The appraisal tool demonstrated high agreement and reliability between reviewers. Conclusion &#x2003;The methodological quality of modern case series is high, except for two quality items that represent an area for potential for improvement for authors of case series describing future pandemics.

Adequate knowledge of first aid for seizures is crucial for medical students, who will eventually be responsible for managing epilepsy patients. The aim of the study was to assess the awareness and attitudes of medical undergraduate students at Tobruk University regarding first aid seizure management. A cross-sectional study was initiated in July 2023 using an online questionnaire that was prevalidated. The questionnaire gathered data on sociodemographic features, a knowledge of seizures and epilepsy, first aid practices, and attitudes toward epilepsy among 317 medical undergraduate students. While 72.9% of students correctly identified a seizure, there were different beliefs about causes, such as some that attributed seizures to supernatural causes (14.2%). There were also deficiencies seen in the knowledge of epilepsy management that included antiepileptic drug treatment duration. It was alarming that 41.6% of students thought that the insertion of some objects into the mouth of a person having a seizure was first aid, which is a well-known hazardous approach. Only 23.6% were correct in the answers that involved the placement of the person in a semiprone position to prevent choking. The study at Tobruk University revealed significant knowledge gaps among medical students about seizure management, with 72.9% correctly identifying a seizure's basic definition, but 41.6% incorrectly believing that inserting objects into a seizing person's mouth is helpful, and only 23.6% knowing the correct first aid position. Students also demonstrated misconceptions about epilepsy causes, including supernatural beliefs, highlighting an urgent need for targeted educational interventions to improve understanding and prepare future health care professionals.

Neuroblastoma (NB) is an aggressive malignant tumor arising from a primitive neural crest origin. While the significance of tumor location in survival outcomes is recognized, it remains inadequately explored. This study provides a comprehensive analysis of the survival and characteristics of pediatric adrenal and nonadrenal NBs in the United States. A retrospective analysis of pediatric primary NB between 1975 and 2016 was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate regression analyses were used to determine prognostic variables. A total of 4,554 patients were included, comprising 52% males ( n &#x2009;=&#x2009;2,385) and 79.2% Caucasians ( n &#x2009;=&#x2009;3,569). The median age of the patients was one year (range: 0-19 years). In all, 44.4% ( n &#x2009;=&#x2009;1,996) of the patients had adrenal NB and 55.6% ( n &#x2009;=&#x2009;2,496) patients had nonadrenal NB. Adrenal NB was significantly more prevalent among males and those presenting at a younger age ( p &#x2009;<&#x2009;0.001). Adrenal NB was more likely to have a higher grade and distant metastasis at diagnosis ( p &#x2009;<&#x2009;0.001). Nonadrenal NB, female sex, surgical resection, and later year of diagnosis were associated with improved survival ( p &#x2009;<&#x2009;0.001). This study highlights important factors that are helpful for prognostication of NB patients in the United States. Tailored approaches considering tumor site are crucial for effective management of NB.

Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease with progressive destruction of bile ducts, cirrhosis, and liver failure. Diagnosis is usually based on detecting antimitochondrial antibodies (AMA), found in 95% of patients with PBC. However, some patients test negative for AMA and other antibodies, which complicates the diagnosis process. We report a case of a 57-year-old Syrian woman who presented with fatigue, jaundice, pruritus, and abdominal pain, and her medical history included colon cancer and chemotherapy. Laboratory tests showed liver fibrosis but were negative for AMA, antinuclear antibodies, and anti-smooth muscle antibodies, further complicating the diagnosis. A liver biopsy was performed and showed mixed fibrosis, cholangitis, and cholestasis, which led to the diagnosis of AMA-negative PBC. This case confirms the importance of liver biopsy in unclear cases of primary cholangitis. This case also highlights the patient's history of colon cancer and chemotherapy as a notable clinical observation, generating a hypothesis for a potential association that warrants further systematic investigation. A better understanding of such variants in PBC can enable early diagnosis and improve management strategies for affected patients.

End-of-life (EOL) care practices, particularly the withholding and withdrawing (W/W) of life-sustaining treatments (LSTs), remain underexplored in North Africa. This study examined factors that influence EOL practices in Morocco. A nationwide online survey was conducted over one month (from July to August 2023) among Moroccan intensivists, assessing their perspectives on W/W LSTs, decision-making processes, and influencing factors, including ethical, cultural, and religious considerations. Univariable analyses were performed to screen for potential associations, followed by multivariable logistic regression to identify factors independently associated with W/W decisions. Of 351 invited intensivists, 151 completed the survey, yielding a 41% response rate. The mean age of respondents was 47&#x2009;&#xb1;&#x2009;9 years, and 84% were male. Most interpreted EOL care as providing palliative care (74%) or ensuring a dignified death (59%), while only 23% explicitly associated it with the cessation of life-sustaining treatment. Nearly 40% reported never having made withholding or withdrawing (W/W) decisions, and 88% made fewer than one such decision per week. While 59% considered withholding LSTs ethically acceptable, only 5% supported both withholding and withdrawing. The most frequently cited barriers were the absence of a legal framework (75%), sociocultural constraints (44%), and discomfort discussing EOL issues with families (58%). Patient wishes were considered in fewer than half of cases, whereas family preferences predominated in 66%. Documentation of W/W decisions was uncommon (27%), and formal institutional protocols were largely absent (94.5%). In multivariable analysis, practicing in a public hospital (odds ratio [OR]&#x2009;=&#x2009;3.16, p&#x2009;=&#x2009;0.005) and believing that Islam permits W/W decisions (OR&#x2009;=&#x2009;3.49, p&#x2009;=&#x2009;0.006) were independently associated with a higher likelihood of making such decisions. Moroccan intensivists face major ethical and practical challenges in EOL care, including legal ambiguity, lack of protocols, limited patient involvement, and difficulty communicating with families. The findings highlight the urgent need for legislative reforms, standardized protocols, and improved education to support ethical, culturally sensitive, and patient-centred EOL practices.

Background &#x2003;Breast cancer remains a significant public health challenge in conflict-affected regions. This study aims to investigate the impact of armed conflict on the burden of breast cancer in female patients in northwest Syria, focusing on clinical presentations, management, diagnosis, access to care, and treatment outcomes. Methods &#x2003;We conducted a retrospective analysis of breast cancer patients diagnosed at the Idlib Oncology Center between March 2017 and January 2022. Data were extracted from clinical files and analyzed in R. The study was conducted at the Idlib Oncology Center, the main referral center for cancer care in northwest Syria, serving a population of 4.6 million. Results &#x2003;A total of 192 patients were included, with a median age of 45.5 years (interquartile range [IQR]: 40-56). Of 108 patients, 56.5% were internally displaced. Most patients were diagnosed with invasive ductal carcinoma (81.3%), and the majority presented at stages II and III (34.8 and 59%, respectively). Among 192 patients, 95.8% underwent surgery, with 96.6% having a mastectomy and 90.7% receiving chemotherapy. The median interval from symptom onset to diagnosis was 100.5 days, that from diagnosis to surgery was 14.5 days, and that from surgery to radiotherapy was 229 days. No significant effect was observed for chemical weapon exposure or family loss on survival. Displacement was associated with significantly lower predicted survival ( p &#x2009;=&#x2009;0.0038; 95% confidence interval [CI]: 0.05064-0.2570). Conclusions &#x2003;This study highlights a high prevalence of late-stage breast cancer, a high rate of mastectomies, delayed access to radiotherapy, and long delays between diagnosis and treatment in northwest Syria. Displacement negatively affects survival rates. Additionally, the substantial lack of radiotherapy in patients needing it and prolonged intervals between treatments contribute to poorer outcomes. Establishing localized oncology services and increasing funding for cancer medications and radiotherapy would improve access to necessary oncology care in this region.

Patients receiving hemodialysis are at high risk for bloodstream infections (BSIs), particularly those with central venous catheters (CVCs). Regional variation in microbial patterns has been reported, with studies from Saudi Arabia suggesting a higher prevalence of gram-negative pathogens compared with Western cohorts. This study aimed to describe the clinical characteristics and microbiology of BSIs among hemodialysis-dependent patients treated within the Ministry of National Guard Health Affairs in Saudi Arabia and to compare findings with international data. We conducted a retrospective, multicenter study across five hemodialysis centers in Saudi Arabia over a 5-year period (January 2019-December 2023). Adult patients (&#x2265;15 years) on maintenance hemodialysis with confirmed BSI based on positive central or peripheral blood cultures were included. Demographic data (including age and body mass index [BMI]), comorbidities, vascular access type, microbiological isolates, and clinical outcomes were evaluated. A total of 437 hemodialysis patients with positive blood cultures were identified, yielding 709 microbial isolates. The study population had a median age of 58 years, and obesity was prevalent (41.7% with BMI >30&#x2009;kg/m 2 ). CVCs were present in 92.7% of BSI episodes, while arteriovenous fistulas or grafts accounted for 7.3%. Hypertension (88%) and diabetes mellitus (60%) were the most common comorbidities. Overall, gram-negative organisms predominated (51.8%), followed by gram-positive organisms (48.2%). Staphylococcus aureus was the most frequent gram-positive pathogen, while Enterobacter cloacae and Klebsiella pneumoniae were the leading gram-negative isolates. Catheter removal was performed in 57.3% of cases, while catheter salvage was successfully attempted in 42.7%. The 4-week mortality was remarkably low (1.14%). BSIs in hemodialysis patients are predominantly catheter-associated and demonstrate a substantial gram-negative burden, differing from traditional Western patterns. High obesity rates and prolonged CVC reliance underscore the need for region-specific prevention strategies, including early permanent access creation, strict catheter management, and antimicrobial stewardship. The favorable mortality rate highlights the effectiveness of current early detection and management protocols.

Osteoporosis is a prevalent skeletal disorder that substantially impairs quality of life (QoL) through reduced bone mineral density, increased fracture risk, and functional decline, particularly in older adults. To evaluate the effects of exercise interventions on health-related quality of life (HRQoL) in adults aged &#x2265;50 years with osteoporosis and to identify the most effective exercise modalities and intervention durations. PubMed (MEDLINE), Web of Science, and Scopus were systematically searched to February 4, 2026, following PRISMA 2020 guidelines. Randomized controlled trials assessing exercise interventions and HRQoL outcomes in adults aged &#x2265; 50 years with osteoporosis were included. Risk of bias was assessed using the Cochrane tool, and certainty of evidence using GRADE. Random-effects meta-analyses were conducted using standardized mean differences (SMDs) for overall mixed-instrument analyses and mean differences (MDs) for subgroup analyses restricted to comparable instruments or domains. Eighteen trials involving 1,591 participants were included, with 1,448 contributing data to the meta-analyses. Exploratory pooling across heterogeneous HRQoL instruments showed no significant overall effect (SMD = -0.18, 95% CI [-0.42-0.06]; I 2 &#x2248; 95%). In contrast, prespecified subgroup analyses demonstrated significant improvements in HRQoL, particularly with resistance training (MD = 10.58, 95% CI [6.79-14.36]) and multicomponent exercise (MD = 5.62, 95% CI [2.65-8.58]). Short-term exercise programs (<20 weeks) produced the most consistent benefits (MD = 9.91, 95% CI [7.27-12.55]). Improvements were observed across physical and mental HRQoL domains. Certainty of evidence was moderate for resistance training and short-term interventions, and low for longer-duration and multicomponent programs. Exercise interventions, particularly resistance training, meaningfully improve HRQoL in adults aged &#x2265; 50 years with osteoporosis. Shorter-duration programs appear most effective, although further high-quality trials are needed to strengthen the evidence base.