BMJ Open Diabetes Research & Care
● BMJ
Preprints posted in the last 7 days, ranked by how well they match BMJ Open Diabetes Research & Care's content profile, based on 15 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.
Adams, J. C.; Pullmann, D.; Belostotsky, H.; Mestvirishvili, T.; Chiu, E.; Oh, C.; Rabbani, P. S.
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ObjectiveThis study evaluates the impact of systemic GLP-1 receptor agonist (GLP-1RA) use on surgical wound healing in high-risk surgical populations, including patients with diabetes, and implications for perioperative planning and healing outcomes. ApproachThis pilot retrospective cohort study compared adult surgery patients with non-healing postoperative wounds by their GLP-1RA use. Outcomes included healing status, time to wound closure, and number of surgical interventions. ResultsThe cohort included 35 non-GLP-1RA users and 16 GLP-1RA users with comparable baseline characteristics, except for significant higher prevalence of venous insufficiency among users. Though median time to closure was similar for all patients, users required fewer surgical interventions and their wounds reached closure in significant difference from non-users. Among patients with diabetes, all GLP-1RA users healed significantly compared to non-users. InnovationThe impact of GLP-1RA therapy on wound healing in high-risk reconstructive and soft-tissue surgery remains poorly defined. This pilot cohort addresses that gap, offering an early signal that GLP-1RA use is associated with improved wound healing and fewer postoperative interventions. These findings may inform perioperative practice by identifying a systemic pharmacologic factor that optimizes surgical outcomes in high-risk populations. ConclusionGLP-1RA use was associated with higher healing rates and fewer interventions, particularly among patients with diabetes. These findings support a beneficial role in surgical wound healing and warrant larger multi-site studies.
Goldwater, J. C.; Harris, Y.; Das, S. K.; Fernandez Galvis, M. A.; Maru, D.; Jordan, W. B.; Sacaridiz, C.; Norwood, C.; Kim, S. S.; Neustrom, K.
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OBJECTIVE: To evaluate the return on investment (ROI) of a community based Diabetes Self Management Program (DSMP) enhanced with health related social needs (HRSN) screening and referrals, implemented by the New York City (NYC) Department of Health and Mental Hygiene with three community based organizations in highly impacted, under resourced neighborhoods. RESEARCH DESIGN AND METHODS: A retrospective cost benefit analysis from a public sector payer perspective was conducted among 171 adults with type 2 diabetes who completed a six week, peer led DSMP delivered by community health workers (CHWs) in English, Spanish, and Korean during 2018 2019. A time driven, activity based costing model captured direct implementation costs, CHW workforce turnover, and administrative overhead. Monetized benefits included avoided diabetes related complications, reductions in self reported emergency department (ED) visits and hospitalizations, and quality adjusted life year (QALY) gains from improved medication adherence. Univariate sensitivity analyses tested robustness under conservative assumptions. RESULTS: Total program costs were $179,224; monetized benefits totaled $1,824,213, yielding a net benefit of $1,644,989 and an ROI of 918%, approximately $10 returned per $1 invested. Excluding QALY gains, ROI remained 551%. Self reported ED visits declined from 149 to 82 and hospitalizations from 93 to 24 in the six months following intervention. Over 80% of participants reported housing instability; 72% were Medicaid covered and 16% uninsured. Sensitivity analyses confirmed a positive ROI under all conservative scenarios. CONCLUSIONS: A CHW led, community based DSMP integrated with HRSN screening and referrals delivered substantial economic and public health value among adults facing housing instability and structural barriers to care. Findings support inclusion of DSMP as a covered benefit in Medicaid managed care, value based payment arrangements, and housing access initiatives to advance equitable diabetes outcomes.
Zhang, R.
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Aims The oral glucose tolerance test (OGTT) is effective for detecting post-load dysglycemia, but it is burdensome and therefore not routinely used. Continuous glucose monitoring (CGM) offers a convenient way to capture real-world glucose patterns, yet it remains unclear whether CGM-derived metrics reflect OGTT-defined dysglycemia. We therefore aimed to evaluate CGM-derived and clinical metrics for predicting OGTT 2-hour glucose, classifying OGTT-defined dysglycemia, and assessing day-to-day repeatability. Methods We analyzed a cohort with paired free-living CGM and OGTT. Multiple CGM-derived metrics and clinical measures were compared for prediction of OGTT 2-hour glucose, classification of OGTT-defined dysglycemia, and day-to-day stability. Predictive performance was assessed primarily by leave-one-out (LOO) R^2, and day-to-day repeatability by intraclass correlation coefficients (ICC). Results The glycemic persistence index (GPI), a metric integrating the magnitude and duration of glycemic elevation, was the strongest single predictor of OGTT 2-hour glucose (LOO R^2 = 0.439). GPI also showed strong day-to-day repeatability (ICC = 0.665) and ranked first on a combined prediction-stability score. For classification of OGTT-defined dysglycemia, HbA1c had a slightly higher AUC than GPI, but GPI plus HbA1c performed best overall, indicating complementary information. Conclusions GPI was a strong predictor of OGTT 2-hour glucose and showed a favorable balance between predictive performance and day-to-day stability, supporting its potential utility as a CGM-derived marker of dysglycemia.
Zhang, H.; Dromard, E.; Tsang, K. C. H.; Guemes, A.; Guo, Z.; Baldeweg, S. E.; Li, K.
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Non-invasive glucose monitoring (NIGM) has been pursued for decades, yet no device has achieved regulatory approval despite numerous studies reporting high accuracy. This systematic review and meta-analysis of 32 studies (38 cohorts: 20 NIGM, 18 iCGM; N = 1,693) investigated methodological factors underlying this accuracy-regulatory gap. The pooled Mean Absolute Relative Difference (MARD) for NIGM (10.21%; 95% CI: 8.73-11.69%) showed no significant difference from iCGM (11.82%; 95% CI: 10.36-13.29%; p = 0.13), with extreme heterogeneity (I^2 = 95.2%). Meta-regression revealed that study duration was the strongest predictor of NIGM accuracy ({beta} = 3.94, p < 0.001), with MARD degrading from 8.7% in short-term to 15.2% in long-term studies, while iCGM accuracy remained stable. Only 15% of NIGM cohorts validated in the hypoglycemia range, compared to 89% of iCGM studies (p < 0.001). These findings suggest that reported NIGM accuracy is substantially influenced by methodological asymmetries.
Fernandes Davies, V.; Perrut, I.; Thow, A.-M.; Duran, A. C.
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Objective: To investigate in the National School Feeding Program (PNAE) the local level drivers and barriers to the implementation of four guidelines: the banning of sugary drinks; restrictions on the procurement of processed and ultra-processed foods; the mandatory increase in weekly servings of fruits and vegetables offered to students; and mandatory direct procurement from family farmers. Design: Qualitative study that used semi-structured interviews. Street level bureaucracy theory informed the theoretical framework and thematic analysis. Setting: Brazilian municipalities, across the country five geographic regions (North, Northeast, Southeast, South, and Midwest). Participants: Stakeholders (e.g. nutritionists, school cooks, and food procurement managers) involved in the local implementation of the PNAE program across the country. Results: Ninety stakeholders were interviewed. Stakeholders reported having autonomy to perform their activities, collaboration and support from other members within the local government and food providers, adequate infrastructure such as a well-equipped kitchens, the availability of trained personnel, and political commitment as drivers for optimum program implementation. Reported barriers included lack of support and resistance to change among cooks, teachers and parents; insufficient physical and human resources; and limited political commitment. When barriers outweighed drivers, interviewees reported adapting their practices, often in restrictive ways that could compromise the implementation of the program. Conclusions: Drivers and barriers to local PNAE implementation were generally similar across studied municipalities, although their magnitude varied. In contexts of greater economic vulnerability and fiscal constraint, additional support and targeted actions from the federal government may be required to strengthen local implementation
Yao, S.; Zimbalist, A.; Sheng, H.; Fiorica, P.; Cheng, R.; Medicino, L.; Omilian, A.; Zhu, Q.; Roh, J.; Laurent, C.; Lee, V.; Ergas, I.; Iribarren, C.; Rana, J.; Nguyen-Huynh, M.; Rillamas-Sun, E.; Hershman, D.; Ambrosone, C.; Kushi, L.; Greenlee, H.; Kwan, M.
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Background: Few studies have examined racioethnic disparities in cardiovascular disease (CVD) in women after breast cancer treatment, who are at higher risk due to cardiotoxic cancer treatment. Methods: Based on the Pathways Heart Study of women with a history of breast cancer, this analysis examines the association between cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events with self-reported race and ethnicity, as well as genetic similarity. Multivariable logistic and Cox proportional hazards regression models were used to test race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 patients in this analysis, non-Hispanic Black (NHB), Asian, and Hispanic women were more likely to have prevalent and incident diabetes than non-Hispanic White (NHW) women. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity. For CVD risk, NHB women were more likely to develop heart failure and cardiomyopathy than NHW women. In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease, which was consistent with the associations found with Native American ancestry. Conclusions: This is the largest multi-ethnic study of disparities in CVD health in breast cancer survivors, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among breast cancer survivors that warrant more research and clinical attention in these distinct, high-risk populations.
Di Somma, S.; Gervais, R.; Bains, M.; Carter-Williams, S.; Messner, S.; Onsongo, N.
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Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.
Alfaro, H. E.; Lara-Arevalo, J.
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Ambulatory Care Sensitive Conditions (ACSCs) are conditions for which effective and timely primary health care (PHC) can prevent hospitalizations. They are widely used as a proxy indicator of access to and quality of PHC. Despite their relevance, evidence from Central America remains scarce. This study aimed to quantify the burden, describe the epidemiological profile, and assess temporal trends of ACSCs hospitalizations in Honduras from 2014 to 2024. We conducted a retrospective observational study using national administrative hospital discharge data from all Ministry of Health hospitals. ACSCs were defined using a standardized list of 20 diagnostic groups based on ICD-10 codes. We estimated percentages and sex-age-standardized hospitalization rates per 10,000 inhabitants. Clinical indicators included length of stay (LOS) and in-hospital fatality rates. Temporal trends were evaluated using joinpoint regression models to estimate annual percent changes (APC). Analyses included stratification by age, sex, and disease category. A total of 4,023,944 hospitalizations were analyzed, of which 547,486 (13.6%) were classified as ACSCs. The overall sex-age-standardized rate was 54.1 per 10,000 inhabitants. ACSCs' standardized rates increased between 2014 and 2018 (APC: 2.7%; 95% CI: -2.4; 15.2), declined sharply between 2018 and 2021 (APC: -17.8%; 95% CI: -30.6; -10.3), and increased again between 2021 and 2024 (APC: 15.9%; 95% CI: 4.6; 37.6). Despite this rebound, rates remained below pre-pandemic levels. ACSCs were concentrated among children under 5 years (27.7%) and adults aged 60 years and older (29.9%). Noncommunicable diseases accounted for 56.8% of cases, with diabetes mellitus as the leading cause. Compared with non-ACSCs hospitalizations, ACSCs were associated with longer LOS (4.9 vs. 3.9 days; p <0.001) and higher in-hospital fatality rates (2.4% vs. 1.7%; p <0.001). ACSCs hospitalizations constitute a substantial burden in Honduras and reflect persistent gaps in PHC performance. Strengthening PHC resilience and capacity, particularly for chronic disease management and vulnerable populations, is essential to reduce avoidable hospitalizations and improve health system efficiency and equity.
Tomasi, J.; Xu, H.; Zhang, L.; Carey, C. E.; Schoenberger, M.; Yates, D. P.; Casas, J.
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Background: Elevated lipoprotein(a) [Lp(a)] is a known risk factor for several cardiovascular-related diseases established from multiple genetic and observational studies. However, the underlying mechanisms mediating the effects of Lp(a) levels on cardiovascular disease risk and major adverse cardiovascular events (MACE) are unclear. The aim of this study was to identify proteins downstream of Lp(a) using mendelian randomization (MR) - a genetic causal inference approach. Methods: A two-sample MR was performed by initially identifying Lp(a) genetic instruments based on data from genome wide association studies (GWAS) of Lp(a) blood concentrations. These instruments were then tested for association with proteins from proteomic pQTL data (Olink from UK Biobank, 2940 proteins and SomaScan from deCODE, 4907 proteins). Results: A total of 521 proteins associated with Lp(a) were identified. Using pathway enrichment analysis, the following MACE-relevant pathways were identified comprising a total of 91 Lp(a) downstream proteins: oxidized phospholipid-related, chemotaxis of immune cells and endothelial cell activation, pro-inflammatory monocyte activation, neutrophil activity, coagulation, and lipid metabolism. Conclusion: The results suggest that the influence of Lp(a) treatments is primarily through modifying inflammation rather than lipid-lowering, thus providing insight into the mechanistic framework which mediates the effects of elevated Lp(a) on atherosclerotic cardiovascular disease.
Yang, H.; Liu, Y.; Kim, C.; Huang, C.; Sawano, M.; Young, P.; McPadden, J.; Anderson, M.; Burrows, J. S.; Krumholz, H. M.; Brush, J. E.; Lu, Y.
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BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [≤]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.
Chen, Q.; Zhang, T.; Zeng, J.; Yam, M.; Lee, S.; Zhou, F.; Zhu, M.; Zhang, M.; Lu, F.; Du, J.; Gillies, M.; Zhu, L.
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PurposeAlanine transaminases (ALT), encoded by the GPT gene, catalyzes the reversible conversion of pyruvate and glutamate to alanine and alpha-ketoglutarate, thereby correlating carbohydrate and amino acid metabolism. However, its role in the human neural retina remains unclear. This study aimed to explore the expression, localization, and metabolic function of ALT in the human neural retina and its potential involvement in retinal diseases. MethodsALT1 and ALT2 expression and localization were examined in the retinas of healthy and diabetic retinopathy (DR) donors via immunoblotting and immunofluorescence. ALT function was assessed in ex vivo human retinal explants using pharmacological inhibition with beta-chloro-L-alanine (BCLA), followed by the analyses of enzyme activity, tissue injury, and transcriptomic responses. Stable-isotope tracing with 13C-and 15N-labelled substrates combined with GC-MS was used to define ALT-dependent carbon and nitrogen fluxes in macular and peripheral retinas. Redox level (NADPH/NADP+) was also evaluated under tert-butyl hydroperoxide-induced oxidative stress. ResultsALT1 and ALT2 were both expressed in the human neural retina, with prominent localization in Muller glia and photoreceptor inner segments. ALT1 displayed a diffuse cytoplasmic distribution, whereas ALT2 demonstrated a punctate pattern consistent with mitochondrial localization. In DR retinas, ALT1 expression was spatially disorganized and heterogeneous, while ALT2 remained comparatively preserved. Inhibition of ALT with BCLA markedly reduced ALT activity without causing overt cytotoxicity or major transcriptional changes. Isotope tracing demonstrated that retinal ALT predominantly channels pyruvate-derived carbon into alanine, whereas alanine was minimally contributed to pyruvate production under basal conditions. ALT inhibition suppressed alanine synthesis and release, redirected nitrogen flux towards glutamate, glutamine, and aspartate, and uncovered distinct metabolic adaptations in macular but not peripheral retinas. Under oxidative stress, ALT inhibition induced the decrease of NADP+/NADPH ratio and LDH release, indicating improved redox balance and reduced tissue injury. ConclusionsALT is previously unrecognized as a regulator of carbon and nitrogen partitioner in the human neural retina, contributing to redox homeostasis under stress. The altered distribution of ALT1 in DR retina and the protective metabolic effects of ALT inhibition suggest ALT as a potential contributor to retinal metabolic vulnerability and a candidate therapeutic target in retinal diseases.
Mhino, F. M.; Ndanga, A.; Chivandire, T.; Sekanevana, C.; Mpandaguta, C. E.; Mwanza, T.; Mutengerere, A.; Scott, S.; Chimberengwa, P.; Dixon, J.; Ndhlovu, C. E.; Seeley, J.; Chingono, R. M. S.; Sabapathy, K.
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IntroductionOver one billion people worldwide have hypertension. In Zimbabwe, prevalence is an estimated 38%, surpassing the global average of 34%, and >50% of hypertensives are undiagnosed. The Community BP groups (Com-BP) study examined whether community groups of people living with hypertension, provided with BP machines and led by trained Facilitators could improve awareness, screening and support for those diagnosed with hypertension, to help blood pressure (BP) control. We present findings from the quantitative evaluation of the Com-BP pilot intervention. MethodsThe acceptability of the Com-BP intervention, its potential effectiveness in improving knowledge, attitudes and practices (KAP) and in reducing BP among hypertensive adults in Zimbabwe, was evaluated. Cross-sectional surveys using standardised questionnaires, and BP and Body Mass Index (BMI) assessments, were done at the start and end of the pilot intervention. Statistical evidence of difference between baseline and follow-up was examined using Wilcoxon signed-rank test for continuous data and McNemars test for categorical data. ResultsFourteen groups (seven urban and seven rural) were formed and 151 participants joined over a median of 5months. Retention in the groups was 97.9% (137/140 recruited at baseline), with approximately equal numbers from the urban and rural sites. Median age at baseline was 54 years (IQR 45-66y; min-max 30-92y) and the majority (79%, n=108) were female. Most participants (82.5%, n=113) rated their experience of the group sessions as excellent. The proportions of participants with changes in KAP from baseline to endline were as follows: 45.3% (n=62) to 81.0% (n=111) (p=0.004) able to identify at least two pre-disposing factors for hypertension; 65.0% (n=89) to 77.4% (n=106) (p=0.02) reporting [≥]1day of vigorous physical activity/week; 28.5% (n=39) to 13.9% (n=19) (p=0.001) reporting salt added to meals at the table. There was no statistical evidence of any difference in medication adherence, p=0.06. The proportion of participants with uncontrolled hypertension was 58.1% (n=79) at baseline and reduced to 31.8% (n=43) at follow-up (p<0.001). DiscussionCommunity groups for improving awareness, detection and support are acceptable and led to improvements in self-reported KAP and prevalence of uncontrolled BP. Further research on the sustainability and impact of the intervention is required.
Hesen, S.; Kassem, K. F.; salah, M. S.
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Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by persistent hyperglycemia, insulin resistance, and chronic low-grade inflammation. Despite the widespread use of established therapies such as metformin, long-term glycemic control remains suboptimal, and disease progression is often not adequately prevented. This highlights the need for novel therapeutic strategies that address both metabolic dysfunction and the underlying immunometabolic components of the disease. In this study, GLX10 (GLXM100) was evaluated as a novel immune modulator in a high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced rat model of T2DM over a 91-day period. Glycemic outcomes were assessed using terminal random blood glucose and oral glucose tolerance testing (OGTT), with glucose exposure quantified by area under the curve (AUC 0-120). Complementary in vitro investigations were performed in hepatic and macrophage cell models to assess cytocompatibility, nitric oxide production, and modulation of pro-inflammatory cytokines, including IL-6 and TNF-. GLX10 treatment resulted in a significant reduction in random blood glucose levels and a marked improvement in glucose tolerance compared to diabetic control animals. Importantly, GLX10 demonstrated greater improvement in OGTT AUC compared to metformin under the same experimental conditions, indicating enhanced dynamic glucose regulation. In vitro, GLX10 maintained viability in normal hepatic cells while significantly suppressing nitric oxide production and inflammatory cytokine outputs in macrophages, supporting a favorable safety and immune profile. Collectively, these findings demonstrate that GLX10 exerts robust antidiabetic activity through a dual mechanism involving metabolic regulation and suppression of inflammatory signaling. The integration of in vivo efficacy with supportive in vitro safety and mechanistic data provides a strong preclinical foundation and supports the further development of GLX10 as a promising therapeutic candidate for T2DM.
Ciudin Mihai, A.; Baker, J. L.; Belancic, A.; Busetto, L.; Dicker, D.; Fabryova, L.; Fruhbeck, G.; Goossens, G. H.; Gordon, J.; Monami, M.; Sbraccia, P.; Martinez Tellez, B.; Yumuk, V.; McGowan, B.
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This updated systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and obesity related complications. Medline and Embase were searched up to 21 November 2025 for randomized controlled trials comparing OMMs versus placebo or active comparators in adults. The primary endpoint was percentage total body weight loss (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and 3 years, anthropometric, metabolic, mental health and quality of life outcomes, cardiovascular morbidity and mortality, remission of obesity related complications, serious adverse events and all cause mortality. Sixty six RCTs (66 comparisons) were identified: orlistat (22), semaglutide (18), liraglutide (11), tirzepatide (8), naltrexone/bupropion (5) and phentermine/topiramate (2), enrolling 63,909 patients (34,861 and 29,048 with active compound and placebo, respectively). All OMMs showed significantly greater TBWL% versus placebo; tirzepatide and semaglutide exceeded 10% TBWL and showed the most favourable glycaemic effects. Semaglutide reduced major adverse cardiovascular events and all cause mortality. In dedicated complication specific trials, semaglutide and tirzepatide showed benefit on heart failure related outcomes; tirzepatide was associated with improved obstructive sleep apnoea syndrome and semaglutide with knee osteoarthritis pain remission. Tirzepatide and semaglutide were associated with improvements in metabolic dysfunction-associated steatohepatitis remission, and semaglutide with improvement in liver fibrosis. No OMMs were associated with an increased risk of serious adverse events. These updated results reinforce the need to individualize OMMs selection according to weight loss efficacy, complication profile and safety.
Ekenze, O.; Scott, M. R.; Himali, D.; Lioutas, V.-A.; Seshadri, S.; Howard, V. J.; Fornage, M.; Aparicio, H. J.; Beiser, A. S.; Romero, J. R.
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Sex specific differences in stroke are recognized. Whether differences in incident stroke risk persists in recent periods needs further elucidation to aid public health preventive efforts. Aim: To determine long-term sex specific trends in stroke and stroke risk factors at different epochs among Framingham Heart Study participants. Methods: We examined age-adjusted 10-year stroke incidence using Cox regression in women and men in five epochs: 1962-1969 (epoch 1, reference), 1971-1976 (epoch 2), 1987-1991 (epoch 3), 1998-2005 (epoch 4), 2015-2021 (epoch 5). We compared stroke incidence by sex across epochs, estimated decade-wise linear trends overall and by sex. We compared risk factors in successive epochs to the first, and estimated sex-specific trends in risk factors. Interactions between baseline risk factors with epoch and trends were assessed by sex. Secondary analyses were repeated in participants <60 years old. Results: Incident stroke occurred in 4.5% (178/3996) in epoch 1, 3.9% (227/5786) in epoch 2, 3.9% (199/5137) in epoch 3, 2.7% (207/7642) in epoch 4, 2.2% (119/5534) in epoch 5. Men had higher risk of incident stroke in each epoch with significant difference in epochs 2 (HR 1.41, 95% CI [1.08, 1.84]) and 4 (HR 1.46, 95% CI [1.11, 1.91]) overall, and in epoch 4 (HR 2.13, 95% CI [1.17, 3.87]) among those <60 years. Stroke incidence declined by 16% per decade in men (HR 0.84, 95% CI [0.79, 0.89]) and 19% per decade in women (HR 0.81, 95% CI [0.76, 0.86]). Among those <60 years, stroke incidence declined by 22% per decade in women (HR 0.78, 95% CI [0.67, 0.95]). Hypertension declined by 8% per decade in women only ([OR] 0.92, 95% CI [0.90, 0.94]), while Atrial fibrillation and diabetes increased in both. Conclusion: Stroke incidence continues to decline in recent periods for women and men. Among participants <60 years, decline was observed only in women, possibly related to decline in hypertension in women.
xia, y.; Sun, L.; Zhao, Y.
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Background: China has implemented policies to strengthen its pharmacist workforce since the 2009 healthcare reform, yet a comprehensive evaluation of their long-term systemic effects is lacking. Objective: To systematically analyze the evolution of Chinas pharmacist workforce in healthcare institutions from 2007 to 2023 across four dimensions: quantity, quality, structure, and distribution, providing an empirical foundation for policy optimization. Methods: A retrospective analysis was conducted using longitudinal data from the China Health Statistics Yearbooks. Trends were delineated via descriptive statistics. Equity and spatial evolution were assessed using the Gini coefficient, Theil index decomposition, and spatial autocorrelation analyses (Global Morans I and hotspot analysis). Results: From 2007 to 2023, the total number of pharmacists increased from 357,700 to 569,500 (average annual growth: 2.2%). This growth lagged behind physicians (4.6%) and nurses (7.4%), causing the pharmacist-to-physician ratio to decline from 1:5.15 to 1:8.39. The workforce showed trends of feminization (female proportion rose from 59.7% to 70.8%) and aging. While quality improved, 51.1% still held an associate degree or below, and only 6.6% held senior titles. Equity analysis revealed the provincial Gini coefficient improved from 0.145 to 0.093. Theil index decomposition confirmed intra-provincial disparities as the primary inequality driver. Spatial analysis showed a non-significant global Morans I by 2023 (0.154, P*>0.05), down from 0.254 (P<0.01) in 2007. Hotspot analysis confirmed this transition, revealing a contraction of high-confidence clusters and a trend toward balanced distribution. Conclusions: China has made measurable progress in expanding pharmacist workforce size and improving inter-provincial equity since 2007. However, persistent structural challenges remain: relative workforce contraction compared to other health professions, an aging demographic, a shortage of senior talent, and significant intra-provincial inequity. Future policies must prioritize optimizing workforce structure and enhancing clinical service capabilities to catalyze a shift toward patient-centered pharmaceutical care.
Chao, H.; Bao, G.; Wang, X.; Tang, B.; Wang, Q.; Hu, Y.; Avolio, A. P.; Zuo, J.
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BackgroundChronic exposure to high-altitude hypoxia imposes sustained cardiovascular stress, yet hemodynamic adaptation among healthy high-altitude dwellers is heterogeneous and remains poorly characterized. This study aimed to identify distinct hemodynamic phenotypes in a healthy high-altitude population using unsupervised machine learning and to evaluate their association with multi-system subclinical target organ damage. MethodsThis cross-sectional study enrolled 694 healthy adults permanently residing at [≥]3300 m on the Qinghai-Tibet Plateau. Unsupervised K-means clustering was performed on nine hemodynamic variables, including peripheral and central blood pressures, augmentation index (AIx), pulse pressure amplification ratio (pPP/cPP), and systolic pressure amplification (pSBP-cSBP). Differences across phenotypes in carotid intima-media thickness (IMT), estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and pulse wave velocity (PWV) were assessed using one-way ANOVA with Bonferroni-corrected post-hoc tests. ResultsThree distinct hemodynamic phenotypes were successfully identified. The C2 (Balanced Adaptation) phenotype (n = 245) demonstrated the most favorable hemodynamic profile, characterized by the lowest blood pressure and augmentation index (AIx) values, along with the highest peripheral-to-central pulse pressure ratio (pPP/cPP). The C1 (Vascular Stress) phenotype (n = 267) presented with normal peripheral systolic blood pressure (125.9 {+/-} 11.3 mmHg) but exhibited markedly elevated wave reflection indices, including the highest heart rate-adjusted augmentation index (AIx@HR75: 31.9 {+/-} 9.7%) and the lowest pPP/cPP ratio (1.29 {+/-} 0.08). The C3 (High-Load Decompensation) phenotype (n = 182) displayed significantly elevated blood pressures and the greatest overall hemodynamic load. Regarding target organ damage, a clear gradient was observed across the three phenotypes. The C3 phenotype showed the highest carotid intima-media thickness (IMT: 1.162 {+/-} 0.23 mm) and left ventricular mass index (LVMI: 69.18 {+/-} 40.73 g/m{superscript 2}). Conversely, the C2 phenotype exhibited the highest estimated glomerular filtration rate (eGFR: 97.38 {+/-} 16.38 mL/min/1.73m{superscript 2}) and the lowest IMT (0.994 {+/-} 0.26 mm). The C1 phenotype consistently displayed intermediate values for all organ damage indicators. After Bonferroni correction, all pairwise comparisons for LVMI and pulse wave velocity (PWV) reached statistical significance (all P < 0.05). ConclusionsHealthy high-altitude individuals manifest three distinct hemodynamic phenotypes arrayed along a cardiovascular risk continuum. The novel Vascular Stress (C1) phenotype represents a "masked" high-risk state characterized by normal peripheral blood pressure but elevated arterial stiffness and wave reflection, challenging sole reliance on brachial pressure for risk assessment. This phenotype-based stratification provides a framework for precision prevention and early intervention in high-altitude populations.
Miura, A.; Okabe, M.; Okabayashi, Y.; Sasaki, T.; Haruhara, K.; Tsuboi, N.; Yokoo, T.
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Background: Single-nephron glomerular filtration rate (GFR) represents a nephron-level functional index that may reveal key pathophysiological mechanisms driving progression in patients with diabetic nephropathy. However, its clinical relevance remains incompletely understood. This cross-sectional study assessed single-nephron estimated GFR (eGFR) across different chronic kidney disease (CKD) stages in patients with advanced diabetic nephropathy. Methods: Nephron number was estimated as the number of nonglobally sclerotic glomeruli per kidney using computed tomography-derived cortical volume combined with biopsy stereology. Single-nephron eGFR was calculated by dividing eGFR by the nephron number of both kidneys. Patients were stratified according to CKD stage at kidney biopsy. Associations between CKD stages and single-nephron eGFR were evaluated using multivariable linear regression models adjusted for age, sex, urinary protein excretion, and eGFR. Results: The study included 105 patients with biopsy-proven diabetic nephropathy and overt proteinuria (median age 59 years, 83% male, HbA1c 6.6%, 57% had nephrotic range proteinuria). The percentage of globally sclerotic glomeruli, mesangial expansion score, and prevalence of nodular lesions increased significantly with advancing CKD stage. Median nephron number declined from 529,178 to 224,458 per kidney, whereas glomerular volume remained constant. Single-nephron eGFR decreased markedly with CKD stage and remained significantly inversely associated with CKD stage after adjustment for clinicopathologic covariates (P for trend <0.001). Conclusion: In overt diabetic nephropathy, single-nephron eGFR decreased with advancing CKD stage, despite relatively preserved glomerular volume. At this stage of disease, structural alterations specific to diabetic nephropathy may impair effective single-nephron filtration capacity.
Nagase, M.; Hino, K.; Sakamoto, A.; Seo, M.
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Patients with amyotrophic lateral sclerosis (ALS) face critical decisions regarding life-sustaining treatments, such as invasive mechanical ventilation and percutaneous endoscopic gastrostomy. Advance care planning and shared decision-making are standard supportive frameworks but they often fail to account for structural pressures like progressive decline, shifting patient values, and fear of becoming a burden that may influence decision-making. This study explores how patients with ALS interpret ventilator and care options amid progressive physical decline, thereby reconsidering approaches to decision support. Using a qualitative descriptive design, the researcher (a nurse/sociologist) conducted 2-3 hour home interviews with five purposively sampled patients with ALS. Data, including eye-tracking-aided responses, were analysed via Sandelowskis framework. Rigour was ensured through team-based triangulation, independent coding by two researchers, and a reflexive audit trail. Subjective narratives were prioritised without medical record cross-referencing to capture patients experiences. Four categories emerged: (1) Rewriting clinical prognosis into a narrative of exploration via peer models, where meeting active ventilator users transformed future perceptions; (2) The conflict between securing care infrastructure and the burden on family, which greatly influenced the will to survive; (3) Existential fluctuation, where patients intentions shifted with daily fulfilment and family events; and (4) Governance of the body via pre-emptive technology use and training carers as physical extensions. Findings showed decision-making was a multi-layered process redefining lifes meaning within social resources. This necessitate shifting from independent to relational autonomy, where agency relies on care infrastructure, not physical ability. Treatment choice is a dynamic exploration requiring narrative companions to support existential fluctuations. Professionals must coordinate environments to reduce patient indebtedness. Limitations include the small, resource-advantaged sample (N = 5) and reliance on subjective narratives without medical record verification. Living with ALS means governing a new self through relational support and continuous dialogue.
Günter, A.; Mühlfriedel, R.; Seeliger, M. W.
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The retinal topography of mammals reflects significant influences of the visual environment. In diurnal species, local specializations, such as the visual streak (VS) for panoramic vision and the area centralis or fovea for binocular vision, play a key role in optimizing visual perception and species viability. While the location of these sites is typically considered the retinal center, the definition of a "central retina" is less clear in nocturnal species. In mice, the most frequently used model in ophthalmologic research, the location of a central retina is hardly discernible in retinal images, neither in retinal structure (OCT sections) nor in vascular organization (SLO and angiography). In this study, we compare the murine retina with that of a diurnal rodent, the Mongolian gerbil (MG). We found that the S-opsin transitional zone (OTZ), a region characterized by the change from S-to M-opsin dominance along the dorsoventral opsin gradient in mice, has a similar relative position in the retina to the VS in the Mongolian gerbil, suggesting an evolutionary positional homology between these regions. Further, since the S-opsin-dominant region is optimized for visualizing the sky and the M-opsin-dominant region for visualizing the ground, the OTZ in between -much like the VS- naturally points toward the horizon. We therefore propose considering the OTZ as the position of a "central retinal area" in mice. Determining the anatomical-physiological center is particularly important to obtain meaningful relative measures such as averages across different retinal areas, as the common referencing to the optic nerve head (ONH) in mice does not take into account retinal organization and the eccentric position of the functional center.