F1000Research

Introduction: Aphasia is an acquired language disorder with a significant negative functional impact. Much of the research on aphasia has focused on word-level language comprehension and production. Further evaluation of discourse-level tasks, both at behavioral and neural levels, will allow for an ecologically valid understanding of the functional implications of language impairment in this population. Method: This study evaluated bilateral frontal, temporal, and parietal cortical activity during computer-based narrative production in 14 young neurotypical individuals, 17 individuals with post-stroke aphasia, and 15 age-matched neurotypical participants using functional near-infrared spectroscopy (fNIRS). Oxygenated hemoglobin (HbO) was measured during narrative production following short video clips and compared to HbO during counting aloud. In addition, behavioral measures quantifying in-task performance were correlated with averaged HbO values. Results: Young neurotypical individuals showed greater cortical activity in bilateral language regions for narrative production compared to counting aloud. In contrast, people with aphasia showed positive condition-related effects in the right frontal ROI and the age-matched group showed positive condition-related effects in the left frontal and right precentral ROIs. Each group showed different patterns in relationships between cortical activity and discourse performance measures. Conclusion: Overall, young participants showing more consistent condition-related effects for narrative discourse production than individuals with aphasia and age-matched controls. This study shows the potential for fNIRS to evaluate cortical activity for ecologically valid language tasks in individuals with post-stroke aphasia.

Aim: Healthy Heart Actions Right Time (HHART) is a multi-phased research project that seeks to identify, implement and evaluate strategies to connect community and clinical activities to reduce the burden of heart disease for Aboriginal and Torres Strait Islander people. The aim in Phase One was to identify priority activities for two participating services. Background: The ongoing effects of colonisation drive a disproportionate burden of heart disease for Aboriginal and Torres Strait Islander people. Clinical and community groups both have established strengths in reducing the risk of heart disease, but these are not always well connected. Methods: Using a case study methodology in two locations we partnered in a 12-month co-design process to identify priority activities to connect clinical and community activities. Findings: Three priorities emerged from the Phase One co-design process: (i) community-led gardening as a strategy to promote heart health through connection and healthy lifestyles; (ii) community days to increase engagement in heart checks and strengthen community-clinic relationship; and (iii) clinic-led development of culturally relevant education resources to promote clinician confidence and community heart health knowledge.

Background: Electrolyte replacement is ubiquitous in the acute care setting, but its familiarity cannot belie that even small dosing errors with potassium can cause lethal cardiac arrhythmias. Recently, MedAgentBench offered a benchmark for agentic artificial intelligence (AI) including the ability to correctly dose potassium based on a single rule; however, this does not adequately reflect the clinical complexity or safety concerns of an agent that has been used as the lethal injection. The purpose of this analysis was to a probe leaderboard large language model (LLM) capabilities to follow basic dosing rules to safely replace potassium in a series of clinician-annotated cases. Methods: Using a clinician panel, we developed a series of dosing principles and 20 clinical cases reflective of the complexity of potassium replacement. External clinicians were surveyed to assess practice variability and agreement to clinician panel answers. We tested GPT-5-chat with each case in triplicate, with and without the clinician curated dosing principles, and prompted the model to answer six questions involving potassium goals, dosing, route, lab frequency, concurrent interventions, and the model's perceived level of confidence for the output and complexity of the case. The primary outcome was the rate of appropriate recommendations in comparison to clinician answers. Results: A total of 54 clinicians reviewed the 20 hypokalemia cases and hypokalemia dosing guideline. Clinicians expressed "highly agree" or "somewhat agree" for 66.8% of the cases evaluated when asked if they agree with the guideline-recommended management. When given the potassium dosing guideline, total errors dropped from 165 to 104, and average accuracy improved from 45% to 65% with GPT-5-Chat. GPT-5-Chat conveyed a high level of confidence for 100% of responses, while labeling 80% and 76% of cases as highly complex with and without the criteria, respectively. Potential harm scores were considerable in both groups, however, a notable reduction in severity scores occurred with the dosing guidance document. Recommendations on concurrent interventions and dosing had the highest rate of errors in both groups. Conclusions: Benchmarks must appropriately reflect clinical complexity to be considered valuable for the deployment of agentic artificial intelligence tools in the healthcare domain. GPT-5-Chat assessment on a comprehensive medication management task for potassium replacement showed improvement with dosing guidance, yet unfit benchmarking performance.

Background: Occupational therapists can improve stroke survivors hand and arm movement and participation in daily activities through action observation (AO). AO involves watching another persons hand or arm complete a movement or task. While research generally supports the use of AO with stroke survivors, there are limited AO videos are available to occupational therapists which makes applying AO challenging. Objective: The purpose of this work is to develop structured and widely accessible tool to support access to AO for stroke survivors, occupational therapists, and researchers. Methods: To develop an AO video library for stroke rehabilitation, functional and non-functional upper limb task deficits were first identified through clinical observations and clinician interviews to establish a prioritized list of daily activities. In collaboration with media production specialists, healthy adult volunteers were recruited and filmed performing these tasks from both first- and third-person perspectives. The recorded videos were then systematically edited, enhanced with instructional title slides, and distributed via a public YouTube channel for clinical application and a categorized digital repository for research purposes. Results: Initial assessments revealed a complete lack of familiarity, awareness, and utilization of AO resources among local occupational therapists, despite high perceived clinical utility. To address this gap, a final library of 150 tasks was established, resulting in the production of 419 finalized, standardized videos featuring six healthy volunteers. For clinical application, these videos were hosted on a free, public YouTube channel organized into 18 functional playlists, while a parallel set was structured into distinct movement categories for research repository storage. Conclusion: By providing a structured and highly accessible tool, this repository enables clinicians, researchers, and caregivers to readily implement evidence-based action observation interventions in both clinical and home settings.

Introduction: Early hospital presentation after stroke onset is necessary for rapid assessment and access to time-dependent acute management. This study examined the correlates of late presentation for stroke care among patients recorded at a tertiary hospital in Ondo State, Nigeria. Methods: A retrospective records review was conducted using secondary data from the Stroke Registry of the University of Medical Sciences Teaching Hospital, radiology department records, referral notes, and ambulance records. Records of stroke cases documented within the preceding 24 months were reviewed. Late presentation was defined as hospital presentation more than four hours after symptom onset. Frequencies, chi-square tests, and modified Poisson regression with robust standard errors were used to estimate adjusted prevalence ratios. Results: The analysis included 371 stroke cases. Of these, 317 (85.4%) presented after four hours, and the median time to presentation was 24 hours (interquartile range: 9-72 hours). Late presentation differed significantly by employment status, first-contact route, and pathway complexity at bivariate analysis. After adjustment, non-hospital first contact remained strongly associated with late presentation: patients whose first documented contact was non-hospital-based had almost 3 times the prevalence of delay compared with those whose first contact was hospital-based (adjusted prevalence ratio = 2.89; 95% confidence interval: 2.15-3.90; p < 0.001). Conclusion: Late presentation was pervasive in this tertiary hospital record cohort and was primarily associated with the initial direction of care-seeking. Stroke response interventions should emphasise immediate hospital presentation and strengthen urgent referral from non-hospital first-contact points.

Introduction: Stroke care is time-sensitive, yet patients in low-resource settings may reach tertiary services only after passing through multiple formal and informal care options. This study examined documented care-seeking pathways and time to presentation among stroke cases recorded at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria. Methods: A retrospective hospital record review was conducted using secondary data from the Stroke Registry, radiology department records, referral notes, and ambulance records at UNIMEDTH. The analysis included 371 stroke cases with documented time from symptom onset to UNIMEDTH presentation and reconstructable care pathways. First-contact routes were classified as hospital/biomedical, self/informal or traditional/faith-based care, and the number of documented steps defined pathway complexity before and including tertiary presentation. Frequencies and percentages described pathway patterns; median presentation times were compared using Mann-Whitney U and Kruskal-Wallis tests. Results: The median time to tertiary presentation was 24 hours (interquartile range [IQR] 9-72), and 317 patients (85.4%) presented after four hours. Only 30 patients (8.1%) presented directly to UNIMEDTH; 44 distinct care-pathway sequences were recorded. Hospital-facility first contact was documented for 81 patients (21.8%). It was associated with a median presentation time of 3 hours (IQR 2-6), compared with 48 hours (IQR 24-72) among patients whose initial contact was outside a hospital facility (U = 699.50, p < 0.001). The median time also differed across grouped first-contact categories and pathway complexity levels (both p < 0.001). Conclusion: Non-hospital or multi-step care-seeking pathways commonly preceded tertiary stroke presentations in this setting. The findings indicate that delayed tertiary arrival is partly embedded in the pathway followed after symptom onset. Interventions should combine public recognition of stroke warning signs with urgent referral linkages involving hospitals, patent medicine vendors, traditional and faith-based providers, and emergency transport systems.

Introduction: Hypertension is the world's leading cause of death, and depression its leading cause of disability. Control rates for these noncommunicable diseases (NCDs) are low in low and middle-income countries (LMICs). Many LMICs have programs to screen and treat underserved communities for infectious diseases, but evidence to adapt them to treat NCDs is limited. We developed and tested a non-communicable disease program through Ghana's Community-Based Health Planning and Services (CHPS) primary care initiative. Methods: We trained 8 CHPS nurses to diagnose and treat hypertension and depression through door-to-door screening and pharmacotherapy. Physician assistants provided telehealth supervision. We combined this treatment with volunteer counseling to boost medication adherence, improve mood, and change health behaviors. We called the 90-day intervention the CHPS Opportunity for Mentally and Behaviorally Integrated NCD Engagement (COMBINE). Results: We recruited 60 adults from 580 screened: 37 with hypertension (mean blood pressure (BP) of 149/91 mm Hg) and 23 with depression (mean physician health questionnaire (PHQ-9) score of 13.3). After 90 days, 57/60 (95%) completed the intervention: 32/37 (86%) achieved blood pressure control (mean BP 122/75 mm Hg), and 19 of 20 (95%) achieved depression control (mean PHQ-9 score 2.0). After 12 months, 51/60 were retained: 33/37 with hypertension (89%) and 18/23 with depression (78%), with a mean BP of 121/75 and PHQ-9 score of 1.4 respectively. All 51 (100%) achieved disease control at 12 months. 5 persons left by migration and 4 by escalation to higher-level care. Conclusions: The COMBINE model achieved high levels of diagnosis, care retention, and disease control, with minimal adverse events, in a remote setting with limited usual NCD care. This model suggests a novel means to improve the care cascade for these and other noncommunicable diseases through existing non-physician care models in LMICs, warranting further controlled testing at scale.

Abstract Objective: The onset of hypertension occurs at a younger age in China, and the relationship between health literacy and quality of life among middle-aged and older hypertensive patients remains unclear. This study explored whether perceived social support and self-efficacy mediate the association between health literacy and quality of life in middle-aged and older hypertensive patients. Methods: A questionnaire was administered to 1,015 middle-aged and older hypertensive adults from communities in six central provinces of China. The EQ-5D scale, Perceived Social Support (PSS) scale, Self-Efficacy Scale (SES), and Health Literacy Scale (HLS) were used to assess quality of life, social support, self-efficacy, and health literacy, respectively. Mplus 8.3 software was used to construct a structural equation model for path analysis. Results: The mean PSS, SES, HLS, EQ-5D, and EQ-VAS scores were 15.57{+/-}3.45, 10.61{+/-}2.41, 9.49{+/-}2.86, 0.88{+/-}0.18, and 71.06{+/-}17.49, respectively. Health literacy and quality of life scores significantly differed among middle-aged and older hypertensive patients, and both showed positive correlations with perceived social support and self-efficacy (both P<0.001). Perceived social support and self-efficacy exhibited a chain mediated effect on the relationship between health literacy and quality of life (EQ-5D utility index and EQ-VAS), accounting for 28.57% of the total effect of the EQ-5D utility index and 27.26% of that of the EQ-VAS. This study is the first to elucidate the mechanism by which health literacy influences quality of life in middle-aged and older hypertensive patients through the chain-mediated effect of perceived social support and self-efficacy. Conclusion : Health literacy is significantly correlated with quality of life in middle-aged and older hypertensive patients. This correlation can directly or indirectly explain the impact on quality of life through mediating pathways involving perceived social support and self-efficacy. Keywords: hypertensive patients, perceived social support, self-efficacy, health literacy, quality of life, mediating effect

Purpose: To evaluate the incidence and baseline predictors of intraocular pressure (IOP)-lowering treatment following detection of referable glaucoma by teleretinal screening. Design: Retrospective cohort study. Methods: Participants were derived from a safety-net teleretinal diabetic retinopathy screening program (2013-2024). Participants included individuals who screened positive for referable glaucoma (cup-to-disc ratio [CDR] [&ge;]0.6 or CDR asymmetry [&ge;]0.2) and completed in-office diagnostic evaluation. The primary outcome was initiation of IOP-lowering treatment (medication, laser, or surgery) and the secondary outcome was intervention with surgery. Cumulative incidence functions were estimated, accounting for loss to follow-up. Fine-Gray models were used to identify baseline screening predictors to risk stratify each outcome. Glaucoma diagnosis was approximated using diagnostic codes and chart review. Results: 2,367 participants were included. The cumulative incidence of treatment was 19.6% (95% CI: 18.0-21.2) at Year 1 and 45.1% (42.1-48.1) at Year 8. Early treatment occurred primarily in glaucoma cases, whereas treatment accumulated longitudinally in glaucoma suspects, reaching 36.5% (31.6-41.5) by Year 8. Surgery was less common (8-year incidence: 5.3%). Baseline screening data predicted treatment and surgery, enabling risk stratification. At Year 8, cumulative incidence differed substantially between high- and low-risk groups (treatment: 59.9% vs. 31.2%; surgery: 9.7% vs. 1.0%). Older age (sub-distribution hazard ratio [SHR] 1.03 per year, p<0.001), Black race (SHR 1.50, p<0.001), and personal history of glaucoma (SHR 1.90, p<0.001) were associated with treatment; Asian race was protective (0.71, p=0.03). Older age (SHR 1.06, p<0.001), worse visual acuity (SHR 5.11 per logMAR unit, p<0.001), and screening at a hospital-based site (SHR 2.46, p=0.003) were associated with surgical treatment. Conclusion: Nearly half of safety-net diabetic patients screening positive for referable glaucoma initiated IOP-lowering treatment over 8 years, while few received surgery. Baseline screening characteristics enabled risk stratification of treatment and surgery. These findings address an evidence gap about longitudinal consequences of screening and suggest that its impact extends beyond detection of prevalent glaucoma to include identification of high-risk glaucoma suspects who warrant ongoing surveillance.

Introduction: Cardiovascular diseases (CVDs) are the leading cause for death and disability worldwide accounting for 75% of deaths in low- and middle-income countries (LMICs) like Nepal. Urbanization and globalization remains the major cause of rise in CVDs among urban poor population along with growth in slum settlements. This study aims to assess the knowledge, attitude and practice (KAP) of CVDs and its risk factors among women of one such urban poor community in Nepal. Methodology: This cross-sectional study (n=388) in the Sinamangal-Minbhawan slum area was conducted using semi structured questionnaire based on STEPs survey and HARDIC study among the participants selected through convenient sampling. Descriptive analysis was done using SPSS version 21 and KAP scores were further categorized based on median score to perform multivariate logistic analysis. Additionally, Anthropometric and blood pressure measurements were also recorded and analyzed. Results: The median age (Interquartile range) of participants was 33 years (17) with majority of them being Dalit by ethnicity, housewives, with up to primary level education belonging to upper lower socioeconomic class. More than half (53.3%) of the participants were obese and over 23% were hypertensive. While half of the hypertensive women were aware of their status, only 3% had their blood pressure under control.The median knowledge, attitude and practice (KAP) scores were 12, 60 and 10 respectively. The KAP scores were positively associated with socioeconomic status of the participants. Conclusion: The study revealed low knowledge with high prevalence of behavioral risk factors of CVDs along with high prevalence of other metabolic risk factors like high body mass index, high waist hip ratio and hypertension among women of slum area with a positive attitude to prevent CVDs and its risk factors.

Introduction: Trans and gender-diverse (TGD) individuals often face stigma and discrimination in healthcare, hindering access to gender-affirming care. Training healthcare workers on TGD health aims to foster inclusive and affirming care practices. This review aimed to evaluate the effectiveness of TGD health training programs for healthcare workers. Methods: This systematic review followed the PRISMA guidelines and was registered with PROSPERO (CRD42023443288). We searched 13 databases for studies up to March 2024, with no language/geographic restrictions. Ten reviewers screened studies in pairs, resolving discrepancies via discussion or third-reviewer input. We included randomized/non-randomized comparative and before-after studies for quantitative analysis (mean difference [MD] or standardized mean difference [SMD] with 95% CIs) and qualitative/mixed-methods studies for thematic synthesis. Evidence certainty was assessed using GRADE (quantitative) and GRADE-CERQual (qualitative). Outcomes included knowledge, attitudes, skills, discrimination, competence, comfort, TGD quality of life, and stakeholder preferences. Results: From 20,188 records, 85 studies were included. Training appears to have improved healthcare workers' knowledge (SMD=1.08, 95% CI 0.78-1.39), attitudes (SMD=0.22, 95% CI 0.05-0.39), skills (SMD=0.96, 95% CI 0.56-1.37), competence (SMD=0.55, 95% CI 0.29-0.81), and comfort (SMD=0.69, 95% CI 0.17-1.21). Qualitative analysis of 130 findings identified 18 categories and four key themes on intervention design and impact. Conclusions: TGD training programs may enhance health workers' knowledge, attitudes, skills, competence, and comfort. Well-structured, interactive, and inclusive programs showed promise, but evidence certainty was low with limited follow-up. Further high-quality research is needed to confirm these findings.

Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.

Background Blood pressure (BP) regulation in individuals with sickle cell disease (SCD) is influenced by a complex interplay of genetic and physiological factors. While SCD has traditionally been associated with lower BP, there is an increased risk of hypertension. Emerging BP research suggests significant heterogeneity across genotypes, age groups, and sex. Objectives: This study investigated the longitudinal effects of population-level characteristics and continuous clinical and laboratory predictors on systolic (SBP) and diastolic blood pressure (DBP) in individuals with SCD, with emphasis on the interactions between baseline and predicted blood pressure slopes over time. Methods We retrospectively analyzed longitudinal data from a cohort of 2,739 patients with diverse SCD genotypes. Descriptive statistics were documented across sex, age range, genotype, health status and relative systemic hypertension risk categories (rHTN-risk). Linear mixed-effects models provided estimates of fixed- and random-effects of baseline BP and of time-related BP effects, respectively. Post-estimation margins provided contrasts of baseline-adjusted BP means and of pre-specified time effects on BP patterns. Results Males had significantly higher baseline SBP ({beta} = 6.64, p < 0.001) but lower baseline DBP ({beta} = -2.61, p < 0.001) compared with age-matched HbSS females. Baseline SBP was more unstable compared with baseline DBP and baseline DBP was more predictive of future BP trends than baseline SBP. Genotype was a consistent predictor of DBP (p < 0.05), but not of SBP. Similarly, we observed increased risks of relative diastolic hypertension across most genotypes, while the prevalence and magnitude of systolic hypertension was lower across all genotype compared with HbSS. Conclusions Blood pressure trajectories in SCD patients are not uniform and are significantly related to genotype, age group and sex over time. Baseline diastolic levels were less heterogenous and exhibited clear upward trajectories over time. These findings support the need for patient-specific BP surveillance in the care and management of SCD.

Objective To determine if it is possible to assess individual patient risk of the development of colorectal cancer (CRC) in people in high-risk groups due to their family history. Design/Method Retrospective observational study of prospectively collected data from consecutive patients referred for a colonoscopy. 2,478 consecutive patients were referred to a single colorectal surgical practice in Sydney, Australia between 1977 and 2018 for a colonoscopy because of a family history of CRC. Of these, 1,963 have been followed for more than 10 years and are the subject of this paper. Histopathological findings categorised as normal (N), non-advanced adenoma (NAA) or advanced neoplasia (AN) with AN proven to be the precursor to CRC. Intervention Colonoscopic screening on the basis of contemporary practice to 2006 and subsequently according to Australian National Health and Medical Research Council guidelines. Results Participants with normal or low-risk findings in the first decade remain at lower risk of CRC for 30 years from the commencement of screening. Conclusion It is possible to stratify individual patients in a high relative risk cohort into those with high or low personal risk of CRC based on colonoscopic findings in the first 10 years of surveillance. Those with no AN in the first ten years have a lower 30-year risk of developing AN than the general community. This offers the possibility of structuring surveillance programs around individual risk rather than group risk, lessening the need for multiple surveillance colonoscopies in the majority of such patients and improving the cost effectiveness of CRC screening at the population level.

Purpose: The purpose of this study was to examine the barriers and facilitators experienced by non-U.S. born persons during the diagnosis and treatment of latent tuberculosis infection (LTBI) in primary care settings, including the impact of culturally and linguistically congruent care navigation. Design: 25 interviews with non-U.S. born patients, along with focus groups and surveys with 31 primary care team members and leadership, were conducted. Setting: The study was conducted within a network of Federally Qualified Health Center (FQHC) clinics. Participants: Participants were adult non-U.S. born patients with LTBI and FQHC care team members. A purposefully selected subsample of randomized participants was interviewed. Intervention: Care navigators followed participants randomized to receive care navigation after a positive test for tuberculosis (TB) infection and offered health navigation and education about the importance of TB screening and treatment. Method: Data collection was followed by thematic analysis guided by a critical ideological paradigm. Results: Culturally and linguistically congruent navigation emerged as central to potentially reducing barriers, fostering trust, and improving treatment continuity. Participants without navigation support reported confusion and disengagement from care, while those with culturally aligned navigators described clarity and comfort, with influence overall by intrinsic motivation, relational support, and culturally shaped beliefs about care. Conclusion: Care navigation that includes culturally and linguistically congruent navigators whenever possible may help increase LTBI treatment completion among non-U.S. born populations. Limitations of the study include the potential influence of cultural norms, power dynamics, and selection bias.

Between 2024 and 2025, Colombia universalized the Electronic Health Invoice with embedded Individual Health Services Delivery Records (RIPS -- Registro Background Between 2024 and 2025, Colombia universalized the Electronic Health Invoice with embedded RIPS records (FEV-RIPS) as the standard for financial and clinical data exchange. ADRES -- the entity responsible for administering the resources of Colombia's General Social Security Health System -- faced the challenge of processing information from multiple heterogeneous sources generated by more than 55,000 healthcare providers. Health systems in high-income countries converge clinical-financial data in consolidated platforms; Colombia started from a fragmented architecture with incompatible historical sources, no cross-database standardization, and no centralized analytical infrastructure until 2023. Objective We describe the design, technical challenges of integrating heterogeneous data, and operational performance of the analytical infrastructure built by ADRES to centralize large-scale processing of Colombian health system information, and derive transferable lessons for health system resource administrators in Latin America facing equivalent digitalization mandates. Methods Technical-descriptive report based on operational metrics from the ADRES Azure/Databricks environment during January-November 2025. We report indicators of data volume, processing speed, computational capacity, concurrent use by functional group, and governance structure. The architecture integrates VPN connectivity with MinSalud, automated processing of multiple formats (XML, relational tables, flat files), and a medallion data lake (Bronze/Silver/Gold). Data quality challenges include structural inconsistencies across sources, coding incompatibilities (municipalities, dates, diagnoses), format heterogeneities in unstructured data, and absent technical documentation. Results The platform manages 21 catalogs, 1,183 tables, and over 110,645 million stored records, with cumulative production exceeding 1 trillion processed records. It executes queries on 100 billion records in ten seconds using clusters of up to 32 TB RAM and 4,096 vCPU. During September-October 2025, monthly query peaks reached 78,028 across eleven functional groups. Integration required Python/PySpark parsers for variable-depth XML, equivalence tables for incompatible municipality codes, cleaning routines for extreme dates used as nulls (1900-01-01, 9999-12-31), and transformation logic bridging classic RIPS and FEV-RIPS. The platform supported econometric analyses, judicial mandate responses, and public interactive dashboards. Conversational AI integration (Genie, Copilot) extends analytical access to users without SQL knowledge. Conclusions ADRES built in one year an analytical infrastructure that provides, to our knowledge, the first published documentation of the systemic technical challenges of integrating heterogeneous data sources in a middle-income social security health system. Centralizing health system information at national scale is technically feasible under public institutional constraints -- but requires solving cross-source standardization problems the implementation literature does not document with quantitative precision. The derived lessons are transferable to health system resource administrators in Latin America facing equivalent challenges.

Background: Pathologic aldosteronism induces oxidative stress, tissue injury, and increases in hemoglobin. Conversely, aldosterone antagonist therapy decreases hemoglobin. Whether these effects are attributable to aldosterone-mediated changes in iron and oxygen metabolism is unknown. Methods: The plasma proteome of participants with overt primary aldosteronism (PA) (n=50) was compared with participants without overt PA (n=61). To isolate aldosterone-dependent effects, participants without overt PA underwent oral sodium suppression testing to quantify the magnitude of renin-independent aldosterone production, enabling monotonic dose-response analyses across the continuum of renin-independent aldosteronism (subclinical to overt PA). Differential abundance testing was performed using empirical Bayes linear modeling, followed by Reactome pathway enrichment analysis and covariate-adjusted sensitivity analyses. To validate clinical relevance, aldosterone dose-response trends with blood count parameters were examined in this cohort, and an independent population-based cohort of 5,713 people with hypertension. Results: 903 proteins in the peripheral circulation were differentially abundant in overt PA versus participants without PA. The most significantly increased protein in overt PA was CYBRD1, involved in iron reduction and absorption. Pathway enrichment identified 16 iron- and heme-related pathways, including erythropoietin signaling, heme biosynthesis and mitochondrial iron-sulfur cluster biogenesis, with increases in heme and erythroid proteins and decreases in mitochondrial iron-sulfur proteins. Linear aldosterone dose-dependent trend analyses across the PA continuum further supported this signature, identifying progressive increases in hemoglobin subunits (HBA1/HBB), heme-related proteins (HMBS, UROS, AMBP, HPX, GLO1) and erythrocyte oxygen handling enzymes (CA1/CA3), alongside progressive reductions in mitochondrial electron transport chain subunits (CYCS, ETFA). These proteomic changes corresponded with aldosterone dose-dependent increases in red blood cell count, hemoglobin, and hematocrit, in this cohort and another population-based cohort. Conclusion: The continuum of PA is characterized by a progressive shift away from mitochondrial oxidative phosphorylation and toward increased intestinal iron absorption, preferential iron transport over storage, and enhanced heme synthesis and recycling, possibly reflecting cellular pseudohypoxia and systemic adaptations to increase oxygen delivery. These findings provide a novel mechanistic basis for aldosterone-mediated tissue injury and the benefits of aldosterone-directed therapy.

Purpose In deprescribing studies, a prescription-free gap is typically used to determine if patients discontinued their treatment. An appropriate gap depends on the typical time between prescriptions during continued use. This work aims to characterise the interval between prescriptions of chronic drugs using different methods for a cohort of older people in primary care in Ireland. Methods The empirical prescription interval was analysed for 38,154 patients for the twenty most common drug classes and the association between covariates and the interval was analysed using a multi-level model. Estimates were also compared to those obtained from the parametric waiting time distribution (pWTD) approach. Results Available covariates had consistent relationships with prescription intervals across drug classes. For example, each additional prescription issue was associated with an increase in the interval by 5.0 (NSAIDs) to 19.7 days ("Other antidepressants"). Full public health cover was associated with a -29.0 day (inhaled adrenergics) to -11.0 day (opioids) change relative to partial cover, while other/private cover had a -17.9 day (benzodiazepines and associated drugs) to -7.1 day (SSRI and SNRIs) change relative to partial cover. The pWTD also produced consistent estimates of the population interval for most drugs. Conclusions The interval varied substantially within drug classes, due to a mixture of patient, practice and unmodelled factors. Variation between practices was effectively explained, with residual variation between patients and within patients. The pWTD approach is useful for describing complex distributions of intervals, and may be more appropriate for inferring a gap than summarising truncated data.

Background: Cervical cancer is the fourth most common cancer in women worldwide and remains a major public health challenge. In Ethiopia, it is the second leading cause of cancer deaths, with around 8,000 new cases and 6,000 deaths each year. Region?specific data on the prevalence and predictors of precancerous lesions remain scarce, yet such information is vital for guiding targeted reproductive health strategies. This study therefore examined the prevalence and predictors of cervical precancerous lesions among women aged 21-60 years undergoing Pap smear screening in public hospitals in Hawassa City, Sidama Region. Methods: An institution-based cross-sectional study was conducted among 241 women attending Pap smear screening at public hospitals in Hawassa City from March to August 2025. Sociodemographic and clinical data were collected via interviews and medical records. Lesions were classified based on the standardized international framework for reporting cervical cytology results from Pap smears per the Bethesda system. Multivariable logistic regression identified predictors p<0.05). Result: Of 241 women screened (mean age 35.3 years), cervical epithelial abnormalities were detected in 52 (prevalence 21.6%). Atypical squamous cells of undetermined significance was the most common abnormality (16.6%). Multivariable analysis showed HIV infection was significantly associated with precancerous lesions (AOR = 3.7, 95% CI: 1.69-8.12, p<0.05), while hormonal contraceptive use was protective (AOR = 0.27, 95% CI: 0.11-0.67, p<0.05). Conclusion: These results underscore the urgent need to strengthen cervical cancer prevention through targeted screening and early intervention. Integrating routine HIV testing with Pap smear programs would be especially valuable. Health authorities should expand accessible screening for women aged 21-60, with particular attention to those living with HIV, to help reduce the burden of precancerous lesions.

Introduction Indigenous peoples in Canada face persistent health inequities rooted in colonialism, systemic racism, discrimination and social exclusion, all of which operate with particular intensity within healthcare institutions. Despite a growing qualitative literature documenting the discrimination and stigmatisation of Indigenous people by healthcare professionals, no validated instrument existed in the Canadian context to measure the stigmatizing attitudes and behaviors of clinicians toward this population. Aim This study aimed to co-develop and validate an instrument using clinical case vignettes designed to capture the affective, cognitive, and behavioral dimensions of stigmatization of indigenous peoples. Method Following Boateng et al.'s three-phase scale development approach, a multidisciplinary team including Indigenous patient partners, researchers, clinicians, and measurement experts generated 244 items across three paired clinical vignettes addressing type 2 diabetes, chronic back pain, and depressive disorder. Each vignette was developed in two versions, one featuring an Indigenous patient (test) and one featuring a non-Indigenous patient (control), distinguished solely by name and origin. Content validity was assessed by an expert committee using a Content Validity Index. The instrument was subsequently administered to a sample of nurses and physicians from two canadian health institutions using a twelve-arm randomization design. Analyses were carried to assess the internal structure of the instrument, convergent and concurrent validity as well as internal consistency. Results Our results show that the instrument developed has good psychometric qualities, particularly in terms of internal consistency, concurrent validity and factor structure, which reflects the theoretical structure assumed. Concurrent validity of the tool with the M-PATAS scale demonstrated weak to moderate significant correlations. Developed through a participatory process centering Indigenous expertise and lived experience, this instrument constitutes a significant methodological advance in the study of racialized stigmatization in Canadian healthcare.