Pharmacoepidemiology and Drug Safety

Background Antibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. Methods We conducted a retrospective analysis of antibiotic importation records from the Tanzania Medicines and Medical Devices Authority for 2010-2016. Systemic antibiotics for human use imported via oral or parenteral routes were included. Unit prices (USD per smallest unit of measure) were summarized using the median and interquartile range (IQR). Prices were compared by route of administration, supplier country, and product naming practice (INN-named versus brand-named) using Mann-Whitney U and Kruskal-Wallis tests with false discovery rate adjustment. Results Of the 14,301 records, 10,894 (76.2%) met the inclusion criteria. Oral antibiotics predominated (89.6%). Although the median oral antibiotic prices declined over time, substantial price dispersion persisted across all study years. Parenteral antibiotics were consistently more expensive (USD 0.755-3.370) and more variable than oral antibiotics. Importation was concentrated in a few medicines, with amoxicillin-clavulanate (16.7%) and amoxicillin (11.4%) accounting for over one-quarter of records, and in a few supplier countries, with India representing 44.9% of the records. Significant price differences between INN-named and branded products were observed for amoxicillin (adjusted p<0.001) and ciprofloxacin (adjusted p=0.018), whereas prices differed significantly by supplier country across major medicines (adjusted p<0.05). Across medicines and years, wide within-product price distributions indicate persistent market segmentation rather than price convergence. Conclusions Antibiotic import prices in Tanzania exhibit systematic and reproducible variations associated with formulation type, supplier origin, and product naming practices. The findings indicate that procurement structure and supplier participation strongly influence pricing in the import-dependent pharmaceutical market. Monitoring import-level prices can serve as an upstream indicator of market conditions and support evidence-informed procurement, pricing regulations, and antimicrobial stewardship policies in LMIC settings.

Hybrid controlled trials (HCTs) incorporate real-world data into randomized controlled trials (RCTs) by augmenting the internal control arm with patients receiving the same treatment in routine care. Beyond increasing power, HCTs may improve recruitment by supporting unequal randomization ratios that increase patient access to experimental treatments. However, HCT validity is threatened by bias from unmeasured confounding due to lack of randomization of external controls, leading to outcome non-exchangeability between internal and external control patients. To address this challenge, we developed a sensitivity analysis framework to assess the robustness of HCT results to potential unmeasured confounding. We propose a tipping point analysis that adapts the E-value framework to the HCT setting where trial participation rather than treatment assignment is subject to confounding. To aid interpretation, we also introduce a data-driven benchmark representing the strength of unmeasured confounding reflected by the observed outcome non-exchangeability. We then propose an operational decision rule and evaluate its performance through simulation studies. Finally, we illustrate the approach using an asthma trial augmented by data from electronic health records. Simulation results demonstrate that our decision rule safeguards against Type I error inflation while preserving the power gains achieved by incorporating external data. In settings where moderate unmeasured confounding led to poorer outcomes for external controls, Type I error was controlled near the nominal 5% level, and power increased by 10-20% compared with analyses using RCT data alone. Our approach provides a practical, interpretable method to assess HCT robustness, supporting rigorous inference when integrating external real-world data.

Background: Platform trials are an efficient trial design which enable testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professional organisations. Participants considered factors related to the consent process and research environment and could provide optional free text responses about additional barriers or facilitators to recruitment. We used descriptive statistics for quantitative data and content analysis for qualitative data. Results: Among 73 respondents, 46 (63%) were female, 36 (50%) were stroke physicians, 24 (34%) nurses, 6 (8%) allied health professionals, and 7 (10%) were in other roles. 36 (49%) had >20 years of clinical experience, 45 (61%) reported spending <10% of their role in research. 66 (91%) thought that a platform trial would be a good option for testing interventions for patients with stroke due to ICH. Across 11 modifiable factors, clinicians most frequently rated perceived importance of the research question as a facilitator of recruitment (94%), while clinician preference for specific treatments was most frequently rated as a barrier (48%). Two themes emerged from free text responses: study design and infrastructure. Regarding study design respondents perceived consent procedures (n=9), study materials (n=8), study procedures (n=8), eligibility assessment (n=6), the research question (n=3) and randomization (n=3) as important for a future platform trial. Regarding infrastructure, emergent factors were staffing (n=17), local research culture and capacity (n=9), research governance and delivery (n=6), and training (n=6). Conclusion: The overwhelming majority of respondents from the UK clinical stroke community supported a platform trial for ICH, although the influence of survey responder bias is unknown.

Background: In low- and middle-income countries, the burden of hypertension is increasing. Medication adherence is a critical component of reducing hypertension-related cardiovascular disease (CVD) risk and death. There are many barriers to hypertension medication adherence, including challenges with access to and possession of medication. To address these challenges, we aim to implement a strategy in rural western Kenya that combines peer delivery of medications and health information technology to improve hypertension medication possession and adherence. Recognizing that stakeholder experience and knowledge can be useful to optimize successful implementation, we sought to assess micro- and macro-level stakeholder perceptions of the planned implementation strategy. Methods: Focus group discussions in both English and Kiswahili were conducted among people living with hypertension, community members, and health workers. In addition, key informant interviews were conducted with public sector health administrators including the program/policy planners for non-communicable diseases at the national and county levels. Content analysis of all transcripts was conducted. A codebook containing deductive codes was generated based on a priori themes identified from the interview guide. These included the perceptions of peers being involved in health service provision, medication delivery, psychosocial support, and the use of health information technology. Emerging themes were also identified and integrated into the results. The investigator team pooled codes according to conceptual alignment and integrated them into common themes after joint review and discussion. NVIVO 12 was used for the data analysis. Results:The PT4A implementation strategy was perceived to have both benefits and potential challenges. Major themes included the importance of trust resulting from a safe space to share experiences with peers, increased access to medications, improved hypertension management at the facility and community levels, and anticipated improved health outcomes for people living with hypertension. The success of the program was felt to rely heavily on the peers competency and how well they communicated, which was viewed as a potential challenge by some stakeholders. Areas of consensus expressed across all participant groups were mostly focused on patient psychosocial support and access to medications. Conclusion: This study was able to identify key perceptions elicited for an implementation strategy that combines peer medication delivery and health information technology to improve hypertension medication adherence. Pre-implementation stakeholder engagement can unearth unique perspectives around perceived benefits and challenges that can be used to refine strategies to increase the success of implementing evidence-based interventions in new contexts.

Objective: Minimum unit pricing (MUP) aims to reduce use of cheap, high strength alcoholic beverages that drive harm, yet concerns remain about inequitable effects for structurally vulnerable groups. As part of the Costs, Harms, Expenditures and Alcohol Prices (CHEAP) study, we linked individual-level, product-specific alcohol consumption data from a customized survey with provincial retail price data to estimate prices per standard drink (PPSD) and examine their association with alcohol-related outcomes across sociodemographic groups. Method: A cross-sectional survey of past-week drinkers in British Columbia, Canada, was linked to provincial product-level alcohol sales data. The population weighted sample included 1,217 adults aged [&ge;] 19 years (716 men; mean age 49.34, SD 16.98). Participants reported product-specific consumption, which was matched to retail prices to calculate individual-level PPSD. Survey weighted quasibinomial models then examined associations between PPSD and three outcomes: (1) causing harm to self or others in the past year, (2) scoring [&ge;] 8 on the Alcohol Use Disorder Identification Test, and (3) consuming [&ge;] 15 standard drinks per week. Analyses were stratified by income, education, subjective social status, and race/ethnicity. Results: Lower price per standard drink was associated with higher odds of harm (OR 3.05, 95% CI 1.25-7.40) and scoring [&ge;] 8 on the AUDIT (OR 2.34, 95% CI 1.37-3.99). Associations were stronger among structurally disadvantaged groups, including low-income respondents and Indigenous participants. Conclusions: Lower alcohol affordability is linked to risky alcohol use, with the strongest effects among structurally disadvantaged groups. MUP would reduce this risk and promote health equity.

Objective To test the effectiveness of a postpartum behavioural intervention delivered by automated text messaging in reducing weight. Design Two parallel group, multicentre, randomised controlled trial. Setting Recruitment from five areas across the United Kingdom (Belfast, Bradford, Stirling, London and Cardiff) through healthcare and community pathways, including social media. Participants A diverse sample of 892 women between 6 weeks and 24 months postpartum, aged 18 years or more and with a body mass index of 25 kg/m2 or more, enrolled between May 2022 and May 2023: 445 were randomised to the intervention and 447 to an active control (comparator). Interventions Twelve months of fully automated text messages with embedded behaviour change techniques and two-way messaging components to support weight loss and maintenance of weight loss in the postpartum period by targeting dietary, physical activity and weight management behaviours. The comparator group received 12 months of text messages on child health and development tailored to child age. Main outcome measures Primary outcome: weight in kilograms at 12 months (end of intervention). Secondary outcomes recorded at 6 and 12 months were changes in weight (at 6 months), body mass index, proportions of women with weight gain or loss of 5 kg or more, waist circumference, self-reported dietary intake, physical activity and infant feeding practices. Results 674 (75.6%) participants were included in the primary analysis. There was no statistically significant difference found in the adjusted mean weight change between the intervention and active control groups (-0.1 kg (95% confidence interval -1.0 to 0.8, P= 0.84). Sensitivity analyses did not change these results. There was a small statistically significant improvement in Fat and Fibre Barometer scores at 12 months in the intervention compared with control group (adjusted mean difference 0.09, 95% CI: 0.04 to 0.14; P <0.001) and a statistically significant increase in physical activity scores (International Physical Activity Questionnaire Short Form) at 12 months in the intervention group compared with the control group (adjusted mean difference 405.3 total MET minutes/week, 95% CI: 141.3 to 669.3; P= 0.003). Conclusions A 12 month automated, interactive behavioural weight management intervention delivered by text message did not support weight loss for postpartum women but did have a positive impact on diet and physical activity behaviours.

Background Persistent inequities in immunisation coverage, particularly among zero-dose and under-immunised children, continue to challenge Pakistan's Expanded Programme on Immunization. Weak feedback loop, inconsistent data quality, and limited real-time monitoring impede effective decision-making. This Implementation Research was conducted under the MAINSTREAM Initiative funded by Alliance for Health Policy and Systems Research (AHPSR) and supported by the Aga Khan Community Health Services Department and National Institutes of Health Pakistan to design, implement, and evaluate a digital monitoring and action planning tool to strengthen data-driven decision-making within routine immunisation systems. Methodology/Principal Findings A co-creation approach was employed to design a digital monitoring solution through inclusive consultations, key informant interviews, and focus group discussions with EPI Punjab at provincial and district levels. The solution included a customised mobile application for data collection and a Power BI visualisation dashboard to map low-coverage areas, identify drivers of dropouts and zero-dose children, and capture caregivers' information sources to inform targeted communication. The intervention was piloted in 60 households across six clusters of a Union Council of District Lahore. Advanced analytics identified reasons for non-vaccination and missed opportunities, generating tailored recommendations and practical plans for program managers. The analysis assessed acceptability, adoption, fidelity, and perceived scalability through field observations, system use, and stakeholder feedback. The co-developed digital tool enhanced visibility of coverage gaps through UC-level mapping, real-time dashboards, and structured action planning. Pilot testing in Lahore showed strong acceptability, ease of use, fidelity, and adaptability among managers, supervisors, and vaccinators. Scalability and sustainability potential were demonstrated, though barriers included leadership turnover, system fragmentation, workload pressures, and resource constraints. Conclusion The tool demonstrated feasibility to strengthen immunisation equity, accountability, and responsiveness. Co-creation with stakeholders enhanced ownership, operational relevance, and adoption, while complementing existing platforms. Sustainability will depend on effective integration, local ownership, capacity building, and accountability, while scalability requires interoperability, resource commitment, policy support, and alignment with existing workflows.

Background Artificial intelligence (AI) is increasingly being integrated into healthcare systems, with growing applications in clinical decision support, workflow optimization, and population health management. While substantial investments have been made in digital infrastructure, the successful adoption of AI in primary care depends critically on the readiness, awareness, and educational preparedness of healthcare professionals. Global health authorities emphasize the need for ethically grounded and workforce-focused approaches to AI integration; however, evidence on clinicians readiness for AI, particularly in primary care settings and in the Middle East region, remains limited. Objectives This study aims to assess the level of awareness, perceptions, attitudes, and educational needs related to AI among healthcare professionals working within Qatars Primary Health Care Corporation (PHCC). In addition, it seeks to examine organizational factors influencing the integration of AI-focused education in primary care and to develop an AI readiness framework that can inform targeted training strategies and policy planning. Methods This study will adopt a mixed-methods design guided by the Organizational Readiness for Change (ORC) framework, adapted for AI integration in primary care. The quantitative component will consist of an anonymous, census-style online survey distributed to all healthcare professionals across PHCC health centers and headquarters, assessing AI awareness, attitudes, training needs, and perceived infrastructure readiness. Composite AI awareness and attitude scores will be calculated, and regression analyses will be used to explore factors associated with AI readiness. The qualitative component will include semi-structured interviews and focus group discussions using maximum variation sampling to capture diverse professional perspectives. Qualitative data will be analyzed thematically, following COREQ and SRQR reporting standards. Quantitative and qualitative findings will be integrated to generate an AI readiness profile and an actionable education roadmap aligned with national digital health priorities. Discussion This study will provide the first comprehensive assessment of AI readiness among primary care healthcare professionals in Qatar. By identifying knowledge gaps, training priorities, and organizational enablers and barriers, the findings are expected to inform the development of evidence-based AI education strategies within continuing professional development frameworks. The proposed AI readiness framework may also offer a transferable model for other health systems seeking to align workforce development with responsible AI implementation in primary care.

Abstract Background: Urinary tract infections (UTIs) are common health issue during pregnancy, often lead to adverse maternal and neonatal outcomes if left untreated, low knowledge contribute to high UTI rates, particularly in resource-limited settings like Jordan. To assess the knowledge levels about UTIs among pregnant women in Jordan and its association with socio-demographic characteristics. Methods: A descriptive cross-sectional study was conducted among 500 pregnant women attending antenatal clinics in four major governmental hospitals across Jordan. Data were collected using a validated questionnaire based on the Theory of Planned Behavior (TPB) comprising 25 questions, including 5 socio-demographic questions and 20 knowledge questions, scores were categorized as "adequate" or "inadequate" based on the median score. Results: Among participants, 51.4% had inadequate knowledge, while 48.6% demonstrated adequate knowledge. Higher knowledge levels were significantly associated with younger age (21-30 years), urban residence, higher education (university and postgraduate), and employment status. Conclusion: The findings highlight a knowledge gap among pregnant women regarding UTIs. Integrating targeted health education and addressing socio-demographic disparities into antenatal care, especially for women with low education and rural residence, may improve maternal outcomes. Keywords: Urinary tract infection, Knowledge, Pregnancy, Antenatal care, Jordan, Maternal health.

Background: Nursing interns are at high risk of psychological distress due to academic and clinical stressors. While poor sleep quality is linked to anxiety and depression, the buffering role of social support remains underexplored in this population. Aims: To explore the role of social support in regulating the relationship between sleep and mental health among nursing interns. Methods: A total of 396 nursing interns completed self-administered questionnaires including the Pittsburgh Sleep Quality Index (PSQI), Social Support Rate Scale (SSRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Hierarchical regression and simple slope analyses were used to test moderation effects. Results: Poor sleep quality was significantly associated with higher anxiety ({beta}=0.449, P<0.001) and depression ({beta}=0.535, P<0.001). Social support significantly moderated these relationships. Under low social support, the effects of sleep quality on anxiety ({beta} = 0.602) and depression ({beta} = 0.779) were stronger than under high support (anxiety: {beta} = 0.396; depression: {beta} = 0.515). Conclusions: Social support buffers the adverse psychological effects of poor sleep among nursing interns. Interventions should integrate sleep hygiene education with strategies to enhance social support.

Purpose: Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact and durability of a concise 3-4 minute video for patient education prior to TGT in community versus academic sites and across cancer types. Patients and Methods: Patients undergoing standard-of-care TGT were enrolled at a tertiary academic institution in three cohorts: Cohort 1-breast cancer; Cohort 2-lung cancer; Cohort 3-other cancers. Cohort 4 consisted of patients with any cancer type similarly undergoing SOC TGT at one of three community cancer centers. Participants completed survey measures prior to video viewing (T1), immediately post-viewing (T2), and after return of TGT results (T3). Outcome measures included: 1) 10-question objective genomic knowledge/understanding (GKU); 2) 10-question video message-specific knowledge (VMSK); 3) 11-question Trust in Physician/Provider (TIPP); 4) perceptions regarding TGT. Results: A total of 203 participants completed all survey timepoints. Higher baseline GKU and VMSK scores were significantly associated with higher income and greater years of education. For the primary objective, there was a significant and sustained improvement in VMSK from T1:T2:T3 (Poverall p<0.0001), with no significant change in GKU (p=0.41) or TIPP (p=0.73). This trend was consistent within each cohort (all p[&le;]0.0001). Results for four VMSK questions significantly improved, including impact on treatment decisions, incidental germline findings, and insurance coverage of testing. Conclusions: A concise, 3-4 minute, broadly applicable educational video administered prior to TGT significantly and sustainably improved video message-specific knowledge in diverse cancer types and in academic and community settings. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.

Introduction: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains limited. Methods: We conducted a retrospective cohort analysis using a large propensity-score-matched population (n = 190,308; 95,154 treated vs 95,154 untreated) to evaluate associations between long-term AIT exposure and incidence of major NDDs. Disease-specific and combined outcomes were assessed across drug classes (NSAIDs, corticosteroids, immunomodulators), sex, age, and therapy duration. Results: AIT exposure was associated with a significantly lower risk of developing any NDD (RR = 0.47, 95% CI 0.43-0.48, p < .0001) and was equally effective in both sexes. Risk reduction was observed for each individual disease: AD (RR = 0.40), non-AD dementia (RR = 0.51), PD (RR = 0.43), MS (RR = 0.25), and ALS (RR = 0.48). Among drug classes, immunomodulators conferred the largest reduction (RR = 0.19), followed by corticosteroids (RR = 0.41) and NSAIDs (RR = 0.42). Duration analyses revealed a graded benefit, with RR declining from 0.94 (<1 year) to 0.25 (>6 years). Risk reduction was strongest in older participants (75-79 years). Discussion: Chronic use of anti-inflammatory or immunomodulatory therapies was associated with substantially reduced incidence of multiple neurodegenerative diseases in both sexes. The strongest effects were observed with immunomodulator use and prolonged therapy duration, suggesting that sustained modulation of systemic inflammation confers broad neuroprotective effects in both sexes. These findings highlight the potential of targeting immune-inflammatory pathways for neurodegenerative disease prevention and can inform prospective mechanistic and interventional studies.

Wearable devices present transformative opportunities for personalized healthcare through continuous monitoring of digital biomarkers; however, individual variations in device wear time could mask or otherwise impact signal identification. Despite the widespread adoption of wearable devices in research, no comprehensive framework exists for understanding how wear time varies across populations or for addressing wear time-related biases in analysis. Using Fitbit data from 11,901 participants in the All of Us Research Program, we conducted the first large-scale systematic assessment of wearable device wear time across demographics, social determinants of health, lifestyle factors, mental health symptoms, and disease. Our findings revealed that wear time was higher among males and increased with age, income, and education, but decreased with depressive, anxiety, and anhedonia symptoms, with reductions more pronounced following clinical diagnoses compared to symptom-based classifications. Individuals with chronic conditions displayed differential levels of wear time compared to healthy controls. Critically, we demonstrate that the widely used [&ge;]10-hour daily compliance threshold, while appropriate for some research contexts, can disproportionately exclude days of data from disease populations: among individuals with major depressive disorder, 74.4% of data days were excluded compared to 20.9% for controls. We propose a flexible methodological framework including standard compliance thresholds, wear time covariate adjustment, metric normalization, propensity score matching, and adaptive thresholds that can be applied individually or in combination to optimize wearable data retention across diverse research contexts. These findings establish wear time as a critical methodological consideration for wearable device research and provide guidance for advancing equitable and rigorous digital health analytics.

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregulated during the mid-secretory phase of the menstrual cycle. In a preclinical model of endometrial epithelial organoids, SE at physiological concentrations activates intracellular cAMP signaling, enhances epithelial metabolism, and upregulates receptivity markers without steroid hormone priming, whereas higher concentrations modestly reduce expression of a key receptivity marker PAEP/glycodelin and shift metabolism towards oxidative phosphorylation. By contrast, in stromal cells lacking detectable GLP-1R, SE disrupts decidualization, induces endoplasmic reticulum stress and suppresses cell-cycle at G2/M phase. Human embryo models, blastoids, expressed GLP-1R and underwent concordant SE-mediated transcriptional remodeling in epiblast and trophectoderm lineages, encompassing changes in metabolism and epigenetic regulation, but without shifts in lineage proportions. Notably, SE increased blastoid attachment to the endometrial epithelium in the absence of exogenous steroid hormones, suggesting enhanced epithelial-embryo interaction. Together, these findings reveal a compartment-specific mismatch, as SE augments epithelial and embryonic metabolic activity but compromises stromal support for implantation, with potential consequences for implantation due to stromal dysfunction.

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we included ambulatory patients aged 6 years or older with genetically confirmed STXBP1-RD. Instrumented 3D Gait Analysis (i3DGA) was performed to objectively quantify gait. Functional mobility was assessed with the Functional mobility scale (FMS) and Mobility Questionnaire 28 (MobQues28). Caregiver health-related quality of life was evaluated using the PedsQL-Family Impact Module (PedsQL-FIM). We explored associations between gait, functional mobility, STXBP1-variant type and clinical features (ID, age at seizure onset, seizure frequency, age at onset of independent walking). Correspondence between i3DGA and the Edinburgh Visual Gait Score (EVGS), an observational gait assessment, was investigated. Results Eighteen participants were included. Compared to typically developing peers, individuals with STXBP1-RD had significantly reduced walking speed, step and stride length. Gait patterns were highly variable, with the most frequent pattern being an externally rotated foot progression angle (FPA), present in 11/18 participants. At home, 93.75% of the participants (16/18) walked independently, yet community mobility was more variable: 11/16 (68.75%) walked independently, 2/16 (12.50%) with aid and 3/16 (18.75%) used a wheelchair, indicating increasing limitations with distance and environmental complexity. Earlier acquisition of independent walking strongly predicted later unassisted ambulation at community level (p<0.001). Median MobQues28 score was 57.14% and median PedsQL-FIM score was 60.42%, indicating a moderate level of mobility limitations and reduced health-related quality of life of caregivers. EVGS was highly positive correlated with i3DGA (p= 0.001). Discussion Quantitative gait analysis in individuals with STXBP1-RD demonstrates heterogenous kinematic deviations, with an externally rotated FPA emerging as the most common pattern. Age at independent walking was a clinically relevant predictor of later functional mobility. EVGS showed strong correspondence with i3DGA and may offer a more practical, semi-quantitative assessment for broader use. These findings inform clinical decision-making and guide the selection of scalable outcome measures for natural history studies and interventional trials.

Background and Purpose: Magnetic resonance imaging (MRI) for radiation therapy treatment planning is currently being used in many anatomical sites to better visualize soft tissue landmarks, a technique known as an MRI simulation. A core component of modern MRI simulation configurations are the use of external laser positioning systems (ELPS) to help set up the patient. Though necessary for accurate and reproducible patient setup, the ELPS, if left on during imaging, may interfere negatively with image quality due to leaking electronic noise, of which MRI is sensitive to. It is currently unknown whether this leakage of electronic noise may further affect quantitative values derived from clinically employed relaxometric, diffusion, and fat fraction sequences. Therefore, in this study, we aim to characterize the impact of MRI simulation lasers on general image quality and quantitative imaging accuracy. Materials and Methods: First, a cine acquisition was used to visualize the real-time changes in image signal-to-noise ratio (SNR) from when the ELPS was deactivated to activated. To validate this effect quantitatively, the SNR was measured using the American College of Radiology (ACR) recommended protocol in a homogeneous phantom with the integrated body, 18-channel UltraFlex small, 18-channel UltraFlex large, 32-channel spine, and 16-channel shoulder coils. Next, a geometric distortion algorithm was tested in two vendor-provided phantoms while using the integrated body coil and the ACR Large Phantom protocol was tested. Finally, a series of quantitative MRI scans were performed using a CaliberMRI Model 137 Mini Hybrid phantom to validate quantitative T1, T2, and ADC while a Calimetrix PDFF-R2* phantom was used for quantitative PDFF and R2*. All scans were performed with both the ELPS both deactivated and activated. Results: Visible electronic noise artifacts were seen when using the integrated body coil when the ELPS was activated on the cine acquisition which led to a four-fold decrease in SNR using the ACR protocol. This SNR drop was not seen when using the remaining tested coils. The automatic fiducial detection algorithm was affected negatively by ELPS activation leading to misidentification when identified perfectly with the ELPS deactivated. Degradation in image intensity uniformity, percent signal ghosting, and low contrast object detectability was seen during ACR Large Phantom testing using the 20-channel Head/Neck coil. Concordance across quantitative MRI values was similar when the ELPS was both deactivated and activated while a consistent increase in standard deviation inside the ADC vials was seen when the ELPS was activated. Discussion: The extra noise induced from the activation of the ELPS during imaging should be avoided due to its potential to unnecessarily increase image noise. This is particularly true when conducting mandatory quality assurance testing for image quality and geometric distortion which utilize the integrated body coil which is most susceptible to ELPS-induced noise. Clear clinical guidelines should be implemented to make this issue known to the MRI technologists, physicists, and other relevant staff using an MRI with a supplementary ELPS for patient alignment.

Despite the relevance of spatial mapping in analyzing the health situation and understanding the risk factors and determinants of leptospirosis, peripheral urban communities often remain invisible on maps, which tend to use data and methods that do not express community contribution nor promote local participation. Furthermore, in the implementation of sanitation interventions, the same happens: there is limited user participation, and a lack of identification of intervention needs based on the perception of community residents, failing the interventions. We conducted a cross-sectional study through collaborative mapping from February to October 2022 with 213 residents and self-declared heads-of-household in two peripheral urban communities. We analyzed the perception of sanitation needs indicated by residents and their relationship with the risk of leptospirosis in these communities. Based on community perception, sewage (NS: 87.1%; JSI/ME: 84.9%) and urban cleaning and solid waste management (NS: 25.9%; JSI/ME: 32.6%) were the sanitation needs. In NS, most participants indicated that the necessary interventions for sewage improvement were actions of sewer cleaning and sealing (26.5%), sewer cleaning and piping (23.5%), and implementation/installation/construction of a sanitary sewage network (41.4%). In JSI/ME, interventions included sewage sealing (48.7%) and piping (25.6%), in addition to actions to maintain sewage cleaning (93.3%). The removal of solid waste (trash) in the square (NS: 22.2%) and on the streets (JSI/ME: 69.2%), as well as community awareness (JSI/ME: 15.4%), were indicated as interventions to meet the needs of urban cleaning and solid waste management. Respondents agreed on where interventions should occur, which congregated around the local river. We found a negative correlation between the predicted leptospirosis seropositivity and perceived intervention needs in both study areas. The prevention of diseases such as leptospirosis in peripheral urban communities requires integrated basic sanitation interventions, encompassing different components and aligned with the local needs perceived by residents.

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.

Background: Quadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. Purpose: The purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study Design: Secondary analysis of previously collected data. Methods: Healthy adolescent athletes completed quadriceps strength testing using an isokinetic dynamometer and a biomechanical assessment during a drop vertical jump task. Quadriceps strength was quantified as peak concentric torque and the peak external KAM was calculated during the landing phase on the dominant limb. Both strength and KAM were normalized to body mass. Linear regression was used to examine the association between normalized quadriceps strength and peak external KAM on the dominant limb. Results: The association between quadriceps strength and peak normalized KAM on the dominant limb was not statistically significant ({beta} = -0.053 (95% CI [-0.137 to 0.030]), F(1,119) = 1.62, R2 = 0.013, p = 0.206). Quadriceps strength explained only 1.3% of the variance in peak KAM, indicating a negligible association between these variables in this cohort. Discussion: Quadriceps strength was not associated with peak normalized KAM during landing, suggesting that frontal-plane knee loading during a drop vertical jump is not meaningfully explained by maximal concentric quadriceps strength alone. KAM appears to be driven more by multi-joint movement strategy and neuromuscular coordination than by the capacity of a single muscle group.

Objectives: Compare Anterior Cruciate Ligament (ACL) Return to Sport after Injury (ACL-RSI) scores over time following ACL reconstruction (ACLR) between male and female patients aged 15 to 25 years with primary ACL injuries and ACL reinjuries. Design: Retrospective cohort design. Setting: Sports physical therapy clinics. Participants: 332 patients aged 15-25 years who underwent ACLR following either primary ACL injury or ACL reinjury, either contralateral or ipsilateral graft reinjury, and had at least one observation of the ACL-RSI. Main Outcome Measures: ACL-RSI score. Results: ACL-RSI scores significantly increased over time post- ACLR (p < .001), males reported significantly higher scores compared to females (p < .001), and patients with contralateral ACL reinjury demonstrated higher scores than those with ipsilateral ACL graft reinjury (p = .006), though there was no difference in scores between patients with primary ACL injury and ACL reinjury. A significant interaction effect of sex and injury status was also observed (p = .009), generally demonstrating that females had lower psychological readiness compared to males across injury statuses. Conclusions: ACL-RSI following ACLR varies based on biological sex and time post-ACLR, though ACL reinjury, independent of the reinjured leg, does not appear to effect scores compared to primary ACL injury.