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The first national HPV-based cervical screening programs began in 2017. Since then, a growing list of countries have moved, or want to move, to HPV-based screening. One of the benefits of HPV-based screening is that a sample does not need to be collected from the cervix by a healthcare practitioner. Self-collection has been demonstrated to give equivalent accuracy as practitioner-collected specimens when a PCR-based clinically validated HPV assay is used. However, there are few clinically validated, PCR-based, HPV assays with on-label claims for self-collection. The current study, Self-Collection or Practitioner-collection Evaluation 2 (SCoPE2), undertook a VALHUDES protocol evaluation with individuals recruited in a colposcopy population in the context of an HPV-based screening program. SCoPE2 recruited 400 participants who each took a self-collected vaginal sample using a FLOQSwab. A practitioner-collected cervical sample was then collected at colposcopy. HPV testing was performed using both the cobas 4800 and the cobas HPV tests. The self-collected specimens demonstrated equivalent and non-inferior relative sensitivity for histologically confirmed CIN2+ (n = 58) when compared with the practitioner-collected specimen for both the cobas 4800 (0.982) and cobas (1.037), but relative specificity was inferior. Additional analyses were undertaken to resolve referral, self-, and practitioner-collected discordant results. SCoPE2 demonstrates that the assessed self-collection method is non-inferior for the detection of CIN2+ when compared with a practitioner-collected specimen.

Despite prevalent gender discrimination in medical education, its influence on personal and professional development, foundational competencies in medical training per the Association of American Medical Colleges (AAMC), remains unclear. This retrospective cross-sectional study assesses how experiences of gender discrimination in medical school influence personal and professional identity formation (PPIF) among males and females. Deidentified student-level data were procured from the AAMC data warehouse for 37,610 MD students who matriculated in 2014-2015 and took the Graduation Questionnaire (GQ) between 2016-2020. Gender discrimination frequency was categorized as 'Never', 'Isolated', and 'Recurrent' from GQ responses to questions about denial of opportunities, offensive remarks, and lower evaluations due to gender. Students self-reported their sex as male, female or declined to answer. PPIF was assessed using two separate GQ metrics assessing student agreement on a 5-point Likert scale that their medical school fostered and nurtured their development as a person and a future physician, respectively, and dichotomized. Female students experienced higher rates of isolated (12.6%) and recurrent (20.1%) gender discrimination than males (4.3% isolated, 6.2% recurrent). Females reported slightly lower personal (71.2%) but similar professional development (92.2%) rates compared to males (73.4% personal, 91.2% professional). Both sexes experiencing gender discrimination had lower likelihoods of PPIF than their counterparts without these experiences. If recurrent discrimination occurred, the aRR (95%CI) of professional development was 0.89 (0.87-0.90) for females and 0.78 (0.74-0.81) for males, while for personal development, it was 0.69 (0.67-0.71) for females and 0.61 (0.58-0.66) for males. Compared to females, males showed sharper declines in professional development as discrimination frequency increased from never to isolated (aRR&#x2009;=&#x2009;0.93, 95% CI [0.92-0.94], p&#x2009;<&#x2009;0.001) and isolated to recurrent (aRR&#x2009;=&#x2009;0.95, 95% CI [0.93-0.97], p&#x2009;<&#x2009;0.001). Gender discrimination negatively influences PPIF for both female and male medical students. Efforts to combat discrimination in medical training and promote holistic student development should be considered. Future work is needed to understand the influence of gender discrimination on the comprehensive development of gender-diverse medical students.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is being identified with increasing frequency worldwide. It arises from a complex interplay of genetic, environmental, perinatal, and socio-demographic influences. A better understanding of these contributing factors is important for improving early identification and guiding preventive strategies. Within this framework, the present study sought to evaluate the perinatal and socio-demographic factors linked to ASD in children aged three to six years. This cross-sectional study, conducted in a hospital setting, took place at a tertiary care center in Bhubaneswar, Odisha, India, between June 2024 and March 2025. A total of 160 children aged three to six years with suspected ASD were included using convenience sampling. Screening was performed using the Trivandrum Autism Behavioural Checklist (TABC), followed by confirmatory diagnosis with the INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD). Data on perinatal factors (gestational age, birth order, mode of delivery, and pregnancy-related complications, including maternal anemia, gestational diabetes, pregnancy-induced hypertension, hypothyroidism, premature rupture of membranes, antepartum hemorrhage, and meconium-stained amniotic fluid) and socio-demographic variables (age, sex, family type, and maternal smoking) were collected. Categorical variables were analyzed using the chi-square or Fisher's exact test, while continuous variables were compared using the independent samples t-test. Odds ratios (OR) with 95% confidence intervals (CI) were computed, and a p-value < 0.05 was taken as statistically significant. Out of 160 children aged three to six years with suspected ASD, 25 (15.6%) were diagnosed with ASD. A significant male preponderance was noted (OR: 3.61; 95% CI: 1.17-11.10; p = 0.026). Maternal anemia (OR: 3.35; 95% CI: 1.39-8.05; p = 0.007) and maternal smoking (OR: 10.22; 95% CI: 3.97-26.29; p < 0.001) were significantly associated with ASD. Children from nuclear families had significantly lower odds of ASD compared to joint families (OR: 0.09; 95% CI: 0.04-0.24; p < 0.001). No other factors showed statistically significant associations. Male gender, maternal anemia, smoking, and family structure were identified as important associated factors. These observations highlight the need to address modifiable maternal risk factors and consider socio-cultural influences in early detection. Further large-scale prospective studies are needed to confirm these associations.

Spiritual health is an important component of holistic health and social care provision; however, previous research highlights a training gap in this area. The SHARP (Spiritual Health Awareness and Recommendations in Primary Care) project used co-design processes informed by the Person-Based Approach (PBA) to develop a training intervention to address this gap. This paper evaluates the process of using co-design within this sensitive, stigmatised topic area that faces challenges in terms of language, identity, power and strongly held values-based opinions. Five co-design workshops were held with a diverse mix of participants including GPs, social prescribers, primary care staff, chaplains, carers, patients and members of the public. Data sources included workshop transcripts, observer notes and post-workshop participant surveys. Thematic analysis was conducted deductively in line with a co-design evaluation framework, where we considered people-level outcomes within and without the co-design group, process outcomes and system-level and sustainment outcomes. Thirty-eight participants took part in the workshops. Analysis identified co-design outcomes at people, group, research process and system-level. Participants valued having space to express views on a sensitive and often taboo topic, with 'being heard' functioning as a prerequisite for engagement and reported high levels of engagement. Professional hierarchies and outsider status persisted despite conscious facilitation efforts, while pragmatic design choices shaped participation, continuity and collective action. The professional mix of participants supported whole-team thinking about implementation, although recruitment of motivated participants may have limited the identification of additional barriers to change. The SHARP project provides important lessons on the use of co-design in sensitive and value-laden research topics. Specifically, for researchers to be attentive to participants' need to be heard, active management of power and hierarchy, and explicit negotiation of pragmatic constraints. Mixed-group co-design can support whole-team thinking about implementation, while reflexive awareness of who is included remains critical to understanding what barriers may be surfaced or missed. Patients, carers and members of the public were actively involved in the design, conduct and interpretation of this study. Public contributors and people with lived experience of primary care were recruited as equal participants within the co-design workshops alongside clinicians and other stakeholders, where they contributed to discussions, activities and decision-making that shaped the content, format and implementation considerations of the SHARP training intervention. Patient and public contributors also informed interpretation of findings through their reflections on workshop processes and perceived relevance to patient care. In addition, members of an established patient and public involvement group were consulted prior to and following the co-design process to advise on acceptability, burden on primary care services and communication of the intervention to patients and the public. Their feedback directly informed refinement of the intervention and dissemination materials.

Subglottic secretion suctioning is an effective measure for reducing aspiration pneumonia and is recommended as a crucial step in artificial airway management for tracheotomy patients. However, this method remains undervalued, and clinical practice is not always evidence-based. This project aimed to promote compliance with best practices for subglottic suctioning in adult tracheotomy patients in the Rehabilitation Department of a 3,000-bed tertiary hospital in China. This project was guided by the JBI Evidence Implementation Framework, which includes the JBI Practical Application of Clinical Evidence System (PACES) and the Getting Research into Practice (GRiP) methods. Evidence-based audit criteria were developed for the baseline and follow-up audits. A total of 168 tracheotomy patients took part in the audits. After the implementation of improvement strategies, a follow-up audit was conducted to measure changes in compliance. The follow-up results showed improvement in three criteria compared with baseline. For Criterion 1, compliance increased by 17.85% (77.38% to 95.23%); for Criterion 2, compliance increased by 96.42% (0% to 96.42%); and for Criterion 3, compliance increased by 46.43% (53.57% to 100%). The difference in nurses' knowledge scores for subglottic suctioning between baseline and follow-up was statistically significant (all p&#x200a;<&#x200a;0.05). Moreover, the rate of aspiration pneumonia, airway mucosal bleeding, and subglottic tube blockage decreased from 27.38%, 20.23%, and 30.95% before implementation to 14.28%, 5.95%, and 10.71%, respectively, (all p&#x200a;<&#x200a;0.05). Evidence-based practices can improve nurses' knowledge of standardized subglottic suction management practices for tracheotomy. Further studies are needed to ensure the sustainability of the project. http://links.lww.com/IJEBH/A556.

The COVID-19 pandemic had a profound impact on people's lives globally and affected access to, utilisation and the delivery of healthcare. Many communities were disproportionally affected by the pandemic. Community-based research approaches may help address potential healthcare inequities by identifying and understanding people's experiences and needs relating to healthcare access and utilisation. For this qualitative study, members of community organisations were trained and supported to interview women from South Asian backgrounds and people seeking asylum and refuge about their experiences of accessing healthcare services and how they looked after their health and the health of others during the COVID-19 pandemic. Twenty-four people took part in a semi-structured interview from four community organisations in West Yorkshire, UK between July and December 2021. The approach to analysis was inductive, using reflexive thematic analysis. Three themes were generated, each with its own subthemes: (1) COVID-19 magnifying existing challenges; (2) Adjusting to shifts and exclusions in healthcare, and (3) Healthcare experiences and trust. Profound psychological and social impacts were evident, with COVID-19 compounding existing life challenges. There was a commitment to following protective actions, despite perceptions of unclear and inadequate Government public health messaging. There were examples of extreme environmental challenges and using adaptation and flexibility to navigate the healthcare system. Perceived limitations of healthcare services were often 'bridged' through the support and advocacy of family and community members. Our findings highlight the significant impact of the COVID-19 pandemic on women from South Asian backgrounds and people seeking asylum and refuge, the inequality and inequity experienced whilst navigating healthcare services and looking after their health and the health of others during the pandemic, and how people adapted to rapidly evolving ways of engaging with the healthcare system. Investment in on-going community partnerships is essential to identify and work with the strengths, skills, resources and knowledge within communities to respond when needs arise. Community researchers were part of the research team and involved in all phases of the research, including reviewing study documentation, participant recruitment and data collection, interpretation of the data and co-authoring this paper.

The COVID-19 lockdown had significant effects on daily life, particularly food security among Australian adults. This study examined the longer-term impact of lockdown measures on food security in Western Sydney, a region more socio-economically challenged within the Sydney area. A total of 548 adults were recruited via convenience sampling at least 6 months post-lockdown (May-August 2022 and January-February 2023). Of these, 523 completed the validated six-item USDA Household Food Security Survey Module and were included in the quantitative analysis. Fifty-four participants took part in 12 focus group discussions (FGDs), including some participants who did not complete the survey. FGDs explored food security perceptions based on its four pillars, both during and after lockdown. Inductive thematic analysis was conducted manually in Excel and verified in NVivo (version 14.23.0). The mean age of survey participants (n&#x2009;=&#x2009;523) was 25.1&#x2009;&#xb1;&#x2009;9.7 years, and 63% were women. Among participants with available birthplace data (n&#x2009;=&#x2009;521), 267 were Australian-born and 254 were overseas-born; birthplace information was missing for two participants. Only 6% reported improved food security post-lockdown. Using the USDA tool, females were significantly more likely than males to report meal size reductions post-lockdown (p&#x2009;=&#x2009;0.0001)> FGDs revealed that food availability, access, utilisation and stability were affected by rising food prices, fear of virus contamination and shifts in shopping habits during and after lockdown. While the measured food insecurity prevalence was low based on the survey findings, the qualitative findings indicated that some participants continued to experience disruptions or vulnerabilities related to food security at least 6 to 15 months post-lockdown. These findings highlight the need for both crisis-responsive and recovery-oriented food security policies, with particular attention to supporting adult women who appear disproportionately affected.

Genomic data sharing enhances efficiency in medical practice by facilitating faster data access and collaboration across settings. However, the same arrangements that enable efficiency could also raise legal inequalities, especially concerning data ownership and access. Yet these inequities are intensified in cross-border collaborations where power dynamics disadvantage low and middle income (LMIC) researchers. A qualitative phenomenological study was conducted in Uganda. Key informant interviews (KIIs) were conducted with 49 stakeholders working at different points across the genomic research landscape and four focus group discussions (FGDs) were conducted with people currently or previously enrolled in genomic studies, or their caretakers. The stakeholders who took part in the KIIs included genomic researchers (16), research ethics committee (REC) members (14), practicing lawyers (3), community advisory board (CAB) members (8) and national research regulators (8). A theory of decolonization was used to clarify rooted power imbalances and unfairness. Through thematic analysis six concerns were identified: (1) inadequate regulatory frameworks, (2) limited access to the shared data, (3) unclear data ownership (4) absence of benefit sharing frameworks, (5) contested intellectual property rights and (6) rethinking power asymmetries and struggles. The wide spread perception by research participants that the Global North collaborators owned the data, eroded community trust. There was limited clarity on data ownership, with Ugandan researchers expressing differing views, on ownership, custodianship, and shared ownership leading to calls for co-ownership. In the absence of benefit-sharing frameworks to regulate the distribution of commercial value, data commercialization disadvantaged Ugandan researchers and participants, reinforcing colonial-like inequalities. Current governance systems mirror colonial patterns in the control and sharing of genomic data in Uganda. These patterns are reinforced not only by cross-border power asymmetries but also by internal power dynamics within the country, including institutional hierarchies and regulatory gaps that limit local decision-making authority. Addressing this requires rethinking governance structures and promoting local or co-ownership models that reflect African interests and support decolonized approaches to data governance. Not applicable. This study did not involve a clinical trial.

To investigate the effectiveness of a physiotherapy protocol in preventing and managing pain in women in the immediate postpartum period after cesarean section. A randomized, parallel, open-label clinical trial, whose data collection took place between October and December 2024, in the rooming-in wards of a Brazilian teaching hospital. The study included 40 women in the immediate postpartum period after cesarean section, randomized into an intervention and a control group (standard care). Participants were asked about the presence of pain when performing movements. If pain was present, they were asked to identify its location, and a Visual Numerical Pain Scale was used to measure the pain score. Participants allocated to the intervention group received the physiotherapy intervention protocol, which consisted of postural guidelines. After 24&#x2009;h, participants in both groups were asked again about the presence of pain in the listed activities. The chi-square and Fisher's exact tests were applied to categorical variables and the t-test for independent samples for pain scores, and the effect size was calculated to determine the magnitude of the associations. A significance level of 5% was adopted for all analyses. Pain complaints were reported in all movements assessed. Pain was felt most frequently in the abdominal region (generalized) and the surgical scar (localized). The intervention had an effect on the movements of coughing, sitting on the toilet, and walking. The physiotherapy protocol effectively reduced pain scores during walking (p = 0.009). Additionally, postpartum women in the intervention group reported greater satisfaction with pain management. The physiotherapy intervention protocol effectively reduced pain scores during walking, with effects on coughing and sitting on the toilet, and increased satisfaction with pain management. Trial Registration: Brazilian Registry of Clinical Trials (ReBEC): UTN: U1111-1308-5716.

Insulin autoimmune syndrome (IAS) is an autoimmune endocrine disorder characterized by hyperinsulinemia, positive insulin autoantibodies (IAA), and hypoglycemia. IAS was previously thought to be induced by drugs containing thiol groups. We describe a case highlighting that IAS may be temporally associated with a proton pump inhibitor (PPI) exposure. This article reports a patient who took beraprost sodium, clopidogrel, atorvastatin calcium, and the PPI pantoprazole and was subsequently diagnosed with IAS, presenting with a high IAA level, refractory hypoglycemia, and markedly elevated insulin levels. The patient's hypoglycemic episodes were ultimately relieved after discontinuation of the PPI, accompanied by a gradual decrease in the IAA level to the normal range. HLA analysis revealed HLA-DRB1*0403, DQB1*0302, and DQA1*0301, indicating the patient's genetic susceptibility to IAS, which was possibly triggered by the PPI. This case report may alert clinicians to possible PPI-associated IAS, helping to avoid misdiagnosis and enable patients to receive timely treatment.

Caregivers of people living with motor neuron disease (plwMND) experience high levels of burden. This study sought to explore the burdens and challenges caregivers faced in their caregiving roles through qualitative investigations of caregiver experiences, to assist in identifying caregivers' priorities for change and improving current caregiving circumstances. The experiences of 12 caregivers of plwMND were explored using a qualitative descriptive methodology. All participants took part in semi-structured interviews, and interview transcripts were analysed via content analysis. Themes developed from the interviews highlighted the complex, interconnected and all-encompassing nature of MND caregiving. This was described across five themes: (1) "It begins before diagnosis," (2) "The relentlessness of care," (3) "Traversing the MND health care and support landscape," (4) "Changes to social connectivity," and (5) "Caregiver well-being." This study highlights Australian caregivers' perspectives on the burden and challenges they face in their roles as caregivers for plwMND. Insights suggested that the MND caregiving role is highly interconnected and pervasive, and caregivers report that they are not always receiving the level of care and support that they and their plwMND require. System-level change that embraces more personalised, integrated, multi-disciplinary models of care for MND is likely to strengthen coordinated access to services and elevate the role of informal caregivers within care teams. Improving caregiver circumstances, support, and well-being could potentially lead to better outcomes for both caregivers and those they care for. Understanding the burdens and challenges experienced by caregivers of people living with motor neuron disease and how they connect within the caregiving role is integral to ensuring that caregivers receive appropriate resources and support.Caregivers report inadequate support, which not only affects caregivers but also affects people living with motor neuron disease(plwMND)&#x2019;s decision-making processes and their access and engagement with health and support services.Due to the all-encompassing and interconnected nature of the burdens and challenges caregivers of people living with motor neuron disease experience, system-level intervention is likely required.Further development of integrated multidisciplinary care models show promise for elevating the status of caregivers within multidisciplinary teams and fostering lateral communication strategies among health and support professionals, easing navigational challenges reported by caregivers.

Inequitable access to health care increases morbidity and mortality among people experiencing homelessness. Peer advocates ('peers') with lived experience may help others to access health care. To evaluate the impact and cost-consequence of Groundswell's Homeless Health Peer Advocacy programme on healthcare access, the processes through which it operates and the impact for peer advocates themselves. A participatory mixed-method design with three components: qualitative study (A), prospective cohort (B), and cost-consequence analysis (C) using cohort and programmatic data. Ethical approval: Dulwich Research Ethics Committee (Integrated Research Application System 271312). London, United Kingdom (2019-23) coinciding with COVID-19 and disruptions to the National Health Service, Homeless Health Peer Advocacy and housing services. Homeless Health Peer Advocacy clients and non-clients (A-C); Homeless Health Peer Advocacy staff, volunteers and homelessness-sector stakeholders (A). Peer advocates accompany clients to healthcare appointments and provide support to address barriers to access. Primary: probability of 'did not attend' at a scheduled outpatient appointment within 12 months of cohort enrolment. Secondary: number of inpatient admissions and accident and emergency visits. (A) In-depth interviews and focus groups; (B) Structured questionnaires and National Health Service Hospital Episode Statistics; (C) Groundswell programme data and cohort findings. Qualitative (A): Peer advocacy empowered clients by building cultural health capitals (skills and communication that support healthcare interactions) and strengthening social and economic resources. Advocates themselves gained social, cultural, human and physical resources, though benefits were greatest for those with some pre-existing stability. Cohort (B): Compared with non-clients, Homeless Health Peer Advocacy clients showed no difference in did not attend rates (rate ratio 0.97, 95% confidence interval 0.67 to 1.42) or accident and emergency visits (mean difference 0.86, 95% confidence interval -0.06 to 1.79) for the other pre-specified outcomes. Clients had 1.14 more inpatient admissions (95% confidence interval 0.52 to 1.75). Sensitivity analyses with imputed data suggested higher numbers of outpatient attendances, outpatient 'did not attends', accident and emergency visits and admissions among clients. Secondary analyses suggested differences by levels of anxiety and depression. Cost-consequence (C): Median annual cost per client was &#xa3;353 (&#xa3;176 per scheduled engagement). Evidence of National Health Service cost saving was inconclusive. The COVID-19 disrupted both Homeless Health Peer Advocacy delivery and National Health Service services. Non-randomised design may have introduced bias. Homeless Health Peer Advocacy enhances clients' cultural health capital and helps peer advocates achieve their goals. We cannot state whether peer advocacy reduces 'did not attends' or demonstrate cost savings, but it was associated with more inpatient admissions and, in sensitivity analyses, more outpatient appointments. Research should explore how peer advocacy addresses stigma in health care and hostel settings and develop outcome measures that capture wider systemic change. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number 17/44/40. Groundswell pioneered Homeless Health Peer Advocacy in London, where people with lived experience of homelessness support others to access health care, a model being adapted by others. Peer advocates provide one-to-one support, helping clients attend healthcare appointments and navigate services. Evidence on the impacts, costs and mechanisms of Homeless Health Peer Advocacy remains limited. Our study asked: how, and to what extent, can peer support change hospital use by people experiencing homelessness? We combined qualitative and quantitative methods. First, we conducted in-depth interviews with peer advocates, clients, homeless people not in the programme and staff in the homelessness sector. These interviews explored how peer advocacy may affect health engagement, well-being, housing and employment. Second, we analysed National Health Service hospital data for 158 people who attended appointments with peer advocates and 153 similar people without advocates, comparing healthcare use over 12 months. Finally, we estimated programme costs and potential National Health Service savings. The research took place during COVID-19 lockdowns when peer advocacy services and wider health care were disrupted. Interviews identified three main mechanisms of peer advocacy: (1) building clients&#x2019; skills to manage their health care, (2) advocating directly with services and (3) providing material or social support. Benefits were reported for both clients and peer advocates, with some peers achieving personal goals through their role. Quantitative findings were mixed. Homeless Health Peer Advocacy did not clearly reduce missed appointments or emergency service use but was associated with more outpatient attendance, particularly among people with moderate anxiety or depression, and more hospital admissions for treatment. Homeless Health Peer Advocacy cost &#xa3;176 per healthcare appointment supported. We found no clear evidence that Homeless Health Peer Advocacy saved National Health Service money, given uncertain effects on service use. In conclusion, Homeless Health Peer Advocacy helps people who are homeless through skills-building, advocacy and support. Future research should examine its role in reducing stigma within health care and hostel settings.

The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.

Transcarotid artery revascularization (TCAR) has assumed a significant role in the surgical treatment of extracranial carotid occlusive disease in current practice. Yet, TCAR specific factors which predispose to periprocedural stroke remain poorly characterized. The purpose of this analysis was to identify factors which may inherently predispose to adverse outcomes in patients undergoing TCAR. We used Vascular Quality Initiative data to examine factors associated with in-hospital stroke after TCAR for patients treated between 2016-2024. We used two complementary machine learning methods to identify factors associated with stroke after TCAR. First, we used classification and regression trees (CART) to identify factors associated with stroke and then grouped patients according to these factors. Second, we used a random forest machine learning technique to identify the top features associated with stroke. Finally, we took the CART-defined subgroups and used logistic regression to account for confounding by the top variables from the random forest. We studied 61,111 patients who underwent TCAR (mean age: 73.4&#xb1;8.9 years, 37.4% women, 42.1% symptomatic). The overall in-hospital stroke risk was 1.33% after TCAR. The CART analysis found that most important factors associated with in-hospital stroke were symptom status, non-compliance with taking a p2y12 inhibitor, and the use of two or more stents. This created four patient groups: (G1) asymptomatic and p2y12 inhibitor compliance, (G2) asymptomatic and p2y12 inhibitor not taking a preoperative P2Y12 inhibitor, (G3) symptomatic and with one stent, and (G4) symptomatic and with 2 or more stents. These groups had in-hospital stroke risk of 0.74%, 1.60%, 1.85%, and 3.96%, respectively. After adjustment for confounding, the groups had a stepwise increase in the likelihood of stroke, G1: reference, G2: adjusted odds ratio (aOR): 1.77 (95% CI: 1.27-2.47), G3: aOR: 2.36 (95% CI: 2.00-2.77), and G4: aOR: 5.29 (95% CI: 4.07-6.87). There appear to be important modifiable factors that are associated with increased periprocedural stroke risk among patients undergoing TCAR. Specifically, unreliable p2y12 inhibition and multi-stent procedures were strong predictors of in hospital stroke. These findings suggest that asymptomatic patients who cannot satisfactorily comply with preoperative medical therapy or symptomatic patients that cannot be treated with a single stent may wish to consider an alternative revascularization strategy.

Within the family Osphronemidae, mouth-brooding fighting fishes are small, air-breathing fish species that hold their eggs and offspring in their buccal cavities as a parental care behavior, usually found in running waters and distributed in the wild throughout Southeast Asia. This study aims to describe the morphological development and generate identification keys for the larval and juvenile stages of seven wild mouth-brooding fighting fish species found in Thailand, i.e., Betta apollon, B. ferox, B. pallida, B. pi, B. prima, B. pugnax, and B. simplex from the wild. The broodstocks were collected from type localities or based on characteristics that most closely matched each species description, with healthy fishes selected and breeding continued for our size-series collection, including B. simplex, a previous study. The results showed that mouth-brooders released their offspring when developed to the post-flexion stage within 11-12 (mode = 11) days after fertilization (DAF), except B. pi, which took 18-20 DAF, and the post-flexion larva developed to the juvenile stage within 18-30 days after release. The main characteristics of the new-release post-flexion larva were an oblong and depressed body, a large head, an oval to rounded eye, and rays where the caudal fin began to develop, as well as having fully developed ventral fins with two or three dorsal, central, and ventral stripes and a caudal spot. Myomere numbers and fin rays differed among species across a range of 8-10 dorsal, 10-13 pectoral, 6 ventral, 24-31 anal, and 10-13 caudal fin rays. Diagnostic characters were selected to create a dichotomous identification key, with an illustration provided. In terms of taxonomy, the different larval stages also differed in pigmentation patterns among species, with pigmentation patterns on head (pre-orbital, sub-orbital, post-orbital, and sub-opercular bands) and longitudinal stripes on the side of the body able to be used to distinguish among different development stages as well as different species.

Phthorimaea absoluta (Meyrick 1917) (Lepidoptera: Gelechiidae) was accidentally introduced into South Korea in 2024 and is currently distributed throughout the country's tomato-producing areas. The interaction of the insect with native alternative host plants in Korea has not been elucidated. Therefore, in the current study, we have determined the oviposition preference and larval development of P. absoluta in Korean native weed and crop plants (two each from Solanaceae). The evaluation of oviposition preference was conducted using a choice and a no-choice test. First-instar larvae of the tomato leafminer were placed on each tested plant and monitored daily for mortality and head capsule measurements to determine larval instars. Accordingly, female adults highly preferred tomato and black nightshade for oviposition, and the highest survival percentage was also observed from these plants. On the other hand, the larvae reared on the eggplant and devil's apple took a longer time to pupate, and the highest mortality was recorded. The positive correlation between larval duration and larval mortality, and the negative correlation between larval duration and pupal weight were observed. The highest growth and fitness indices were observed in larvae reared on tomato and black nightshade. Collectively, tomato leafminer can complete its life cycle on all the tested plants with varying performance. Therefore, it is important to consider these plants as potential alternative hosts in predicting the insect abundance and planning the integrated pest management strategies of the pest.

Systemic glucocorticosteroids (SGCs) are recommended only for short-term treatment of atopic dermatitis (AD) because of their side effect profile. Nevertheless, prolonged and repeated use remains common in routine care. Evidence on whether treatment duration or cumulative dose is the main driver of adverse events is limited. Therefore, the aim of this study is to investigate the longitudinal association between SGC treatment duration and side effects in persons with AD and to compare its impact with cumulative dose. This was a retrospective cohort study based on German statutory health insurance data that included persons with AD initiating SGC therapy. Associations between SGC exposure and side effect were analyzed using logistic regression and adjusted time-dependent Cox models. Longer treatment duration was associated with higher odds of multiple side effects, including osteoporosis (odds ratio [OR] 1.21-1.27). In time-dependent Cox models, each additional quarter of SGC therapy increased the hazard of mental disorders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.10-1.32), gastritis/duodenitis (HR 1.07; 1.00-1.15), osteoporosis (HR 1.37; 1.23-1.52), hypertension (HR 1.26; 1.08-1.48), and diabetes mellitus (HR 1.35; 1.09-1.69). Prolonged SGC therapy is associated with increasing risks of multiple side effects, supporting guideline recommendations for short-term use only. Documented SGC treatment duration showed more consistent associations with side effects than cumulative dose. Atopic dermatitis is a chronic skin condition characterized by itching and inflammation, which can occur in flare-ups. It is estimated that around 3.6 million persons in Germany are affected by atopic dermatitis. Systemic glucocorticosteroids are a widely used medication for the treatment of atopic dermatitis, but owing to their many side effects, they should only be used for short-term treatment. Contrary to this recommendation, however, studies show that prescriptions are often longer than necessary. This study therefore examines the duration and dosage of systemic glucocorticosteroid prescriptions, as well as the associated risk of side effects, in individuals with atopic dermatitis. To this end, we evaluated anonymized billing data from a large German health insurance company, including persons with atopic dermatitis who received a new systemic glucocorticosteroid prescription. Our findings show that the length of systemic glucocorticosteroid treatment mattered more for adverse events than the total amount prescribed. Thus, we observed persons with atopic dermatitis and systemic glucocorticosteroid prescriptions until new side effects occurred. The longer individuals took systemic glucocorticosteroids, the more frequently side effects occurred. This was particularly evident in cases of gastritis/duodenitis, osteoporosis, high blood pressure, and diabetes. Our findings support the systemic glucocorticosteroid prescription recommendation and show that the duration of systemic glucocorticosteroid therapy has a great impact in adverse events. However, a short-term prescription for severe acute flare-ups can be helpful. Other systemic therapies are recommended for long-term treatment.

Diagonale des fous inclusive (DDFI) was an initiative to raise awareness towards disability inclusion, generate opportunities in inclusive outdoor leisure-time physical activity, and enhance quality of participation (QoP). QoP is defined as a broad subjective evaluation of satisfaction, enjoyment, and perception of personally valued outcomes that comprises of six experiential elements, including autonomy, belongingness, challenge, engagement, mastery, and meaning. For two years, the participants in this project took part in trail events across Quebec to prepare before culminating their journey on R&#xe9;union Island with a 105-km ultra-trail, one of the biggest ultra-trail events in the world. The aim of this study was to explore QoP and the conditions that shape it among team members preparing for and participating in the DDFI. This study used a qualitative ethnographic design (descriptive and interpretative). Twenty-three participants (aged 26-67 years old; 3 people with a disability, including one adapted all-terrain wheelchair-user) were recruited using purposive sampling. QoP was explored using semi-structured interviews (n&#x2009;=&#x2009;19 before DDFI, n&#x2009;=&#x2009;19 after DDFI). Participant observations were conducted during preparation activities and during the DDFI. Field notes were collected during participant observations to contextualize the data. Thematic analysis was instigated using a mixed approach (deductive and inductive). Four overarching themes were extracted from data: (1) A Human Experience illustrates the life of having a diverse and inclusive group; (2) Long Way to the Top represents the reality of long-term engagement; (3) Call of the Wild encompasses a spectrum of motivations and emotions related to adhesion; and (4) Paving the Way highlights the meaning of DDFI in relation to awareness. This study offers insight into the team's QoP through the experiential elements of autonomy, belongingness, challenge, engagement, mastery, and meaning. Some conditions to the six elements were highlighted, such as inclusion, experiencing a role, group environment, and spreading awareness towards disability inclusion. Further studies are needed using community-accessible trail opportunities that are inclusive to PWDs to expand on these outcomes.