Low Sample Size Research Articles

A systematic literature review of studies assessing first-line (1L) treatments in patients with advanced, grade 2/3 (G2/G3) gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

663 Background: There is no universally accepted standard of care for newly diagnosed patients with G2/G3 advanced GEP-NETs. The phase 3 NETTER-2 trial showed that [ 177 Lu]Lu-DOTA-TATE plus long-acting octreotide demonstrated a significant improvement in progression-free survival (PFS) vs. high-dose long-acting octreotide alone in this patient population. We conducted a comprehensive review of the published literature to summarize the available evidence on other 1L treatments assessed in advanced, well-differentiated, G2/G3 GEP-NETs. Methods: Embase, MEDLINE, and CENTRAL were systematically searched (until Jan 2024) to identify relevant clinical trials and observational studies assessing 1L systemic therapies among adults with advanced, well-differentiated, G2/G3 GEP-NETs. Key conferences from the past three years were also reviewed. Comparators of interest included somatostatin analogues (SSAs; octreotide and lanreotide), targeted therapies (sunitinib and everolimus), and chemotherapies (CAPTEM, STZ+5-FU, FOLFIRI, and platinum-based therapies). Studies with mixed patient populations were also included if ≥80% of the study participants matched the eligibility criteria. The 2022 WHO classification system was applied in studies with available Ki-67 index data but lacking grade information. Results: A total of 31 studies met the review eligibility criteria (three randomized controlled trials, one open-label extension study, three single-arm trials, and 24 observational studies). None of the included studies entirely matched the NETTER-2 population but provided data only for specific sub-populations. The included studies were categorized either by overall GEP-NET (n=16) or pancreatic-NET only population (n=15) with no study exclusively assessing gastrointestinal-NET patients. Majority of the comparator studies assessed chemotherapies (n=14), followed by SSAs (n=10), targeted therapies (n=3), a combination of targeted therapy and chemotherapy (n=1), and mixed treatments (n=2). Heterogeneity was also observed in terms of patient characteristics (data reported only in 12 studies), sample size (<50 patients in 20 studies), and disease grade (G2/G3: nine studies, G2 only: 12 studies, and G3 only: 10 studies). Grading was derived using Ki-67 index in two studies. Majority of the studies reported PFS data (n=22), with nine studies providing data for both PFS and overall survival (OS); Kaplan-Meier curves for PFS and OS were reported for only 13 and four studies, respectively. Conclusions: This systematic literature review highlights a substantial evidence gap and an unmet need in 1L treatment of G2/G3 GEP-NETs. Robust quantitative comparison of NETTER-2 data with published evidence on other 1L treatments was largely restricted by low sample sizes and the aforementioned heterogeneity.

P0406 Complications after ileal pouch-anal anastomosis in patients with Ulcerative Colitis and primary sclerosing cholangitis

Abstract Background Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a common treatment approach for patients with primary sclerosing cholangitis (PSC) and medically refractory ulcerative colitis (UC) or colorectal dysplasia. Patients with PSC-UC are more likely to experience pouchitis, chronic pouchitis and pouch failure than patients with UC alone (1, 2). The aim of retrospective study is to compare rates of pouch complications and need for biologics in UC IPAA patients with and without PSC. Methods We performed a retrospective cohort study of patients who underwent IPAA surgery between March 2015 and February 2024 at our tertiary referral centre. According to the internal hospital protocol, pouchoscopies and clinical examination were performed 1, 3, 6, and 12 months after restoration of the faecal stream. Demographics, comorbidities, pouchitis frequency (as by clinician assessment), laboratory tests and medication use were collected from the electronic medical records and compared between groups for the first year following IPAA surgery, and at last follow-up. Descriptive and univariate analyses was performed. Fisher’s exact test was used to compare frequency of pouch complications (pouchitis, need for biologics and pouch failure) between PSC-UC and UC group. Results In our cohort there were 186 patients with UC that underwent IPAA surgery, among them 14 (7.5%) with concomitant PSC. After a similar follow-up between both groups (p=0.99), patients with PSC-UC compared with UC only were more likely to develop pouchitis at any given timepoint, month 1 (n=173: 14.3% vs 10.7 %, p=0.65), month 3 (n=149: 36.4% vs 16.7 %, p=0.11), month 6 (n=154: 25% vs 22.5%, p=1.0), month 12 (n=144: 41.7% vs 18.9%, p=0.13). By month 12, 92.9% of PSC-UC patients had developed pouchitis compared to 61.0% in the UC only group (n= 178, RR 1.52, 95% confidence interval (CI) 0.19-11.92, p=0.02) Fig 1. After a median follow-up of 24 months, the need for biologics in PSC-UC group tended to be higher (n=163: 30.8% vs 12.7%, RR 2.43, 95% confidence interval (CI) 0.68-8.66, p=0.09). Pouch failure tended to occur more frequent in the PSC-UC group (n= 163: 7.7% vs 4.0%, RR 1.92, 95% confidence interval (CI) 0.21-17.31, p=0.45). Conclusion Percentage of patients with at least one episode of pouchitis in the first year after IPAA surgery was significantly higher in UC-PSC group. Additionally, patients with PSC-UC after IPAA surgery appear to be at higher risk for pouch complications, such as pouchitis, the need for biologics and pouch failure, however statistical significance was not achieved due to a low sample size in UC-PSC group. References (1)Barnes EL, Holubar SD, Herfarth HH. Systematic review and meta-analysis of outcomes after ileal pouch-anal anastomosis in primary sclerosing cholangitis and ulcerative colitis. J Crohns Colitis. 2021;15(8):1272-1278. doi:10.1093/ecco-jcc/jjab025 (2)Quinn KP, Urquhart SA, Janssens LP, Lennon RJ, Chedid VG, Raffals LE. Primary sclerosing cholangitis-associated pouchitis: A distinct clinical phenotype. Clin Gastroenterol Hepatol. 2022;20(5): e964-e973. doi: 10.1016/j.cgh.2021.02.006

P1222 The macroscopic and microscopic distribution of IBD in patients with PSC: a polytomous latent class analysis on 3177 endoscopies

Abstract Background Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) is a distinct disease entity requiring specific management1. Data on characterisation of the phenotype of PSC-IBD are limited and subclassification is lacking. Therefore, this study aims to describe the macroscopic and microscopic distribution of IBD in patients with PSC. Methods A retrospective analysis was conducted on data from PSC-IBD patients included in the EpiPSC2 registry, comprising patients from 46 hospitals across the Netherlands. Data on inflammation at macro- and microscopic level in the ileum and 6 colonic segments were collected on every available endoscopy. Data after (hemi)colectomy were excluded. Polytomous latent class analysis was used to identify subgroups of IBD distribution2. First, latent class models (LCM) were fitted on all endoscopic and histologic data and Akaike and Bayesian information criteria were used to determine the optimal number of classes. After random sampling with replacement the LCM with the ideal number of groups was fitted on 20 samples of one endoscopy with inflammation per subject, and the pooled class probability was calculated per subgroup. Results A total of 3177 endoscopies from 522 PSC-IBD patients (median of 5 [IQR 2-9] endoscopies per patient) were included. The maximum depth of insertion was the terminal ileum in 62% and caecum in 27% of endoscopies. Macroscopic inflammation was observed in 1521 (48%) endoscopies from 428 patients. Segmental colon biopsies were obtained during 650 (20%) endoscopies in 237 subjects, and ileum biopsies in 144 (22%) endoscopies in 100 subjects. Microscopic inflammation in any segment was observed in 265 (41%) endoscopies. An LCM with four classes was the best fit to the macro- and microscopic data: no inflammation, right-sided colitis (pooled class probability 36%), left-sided colitis (30%), and pancolitis (34%). In right-sided colitis and pancolitis the probability of ileal involvement was 16% and 22%, whereas left-sided colitis most often displayed an absence of ileal involvement (probability of 4%) [fig.1]. For microscopic inflammation no pooled class probabilities could be calculated due to low sample size. In 139 (21%) endoscopies, LCM showed more extensive inflammation at microscopic assessment as compared to macroscopic assessment. Conclusion Macroscopic and microscopic inflammation in PSC-IBD may be classified into right sided colitis, left sided colitis, and pancolitis. The microscopic extent exceeds macroscopic inflammation in over 20% of endoscopies with segmental biopsies. Future research into the prognostic implication of this subclassification on PSC- and IBD-related outcomes is required.

A systematic meta-analysis of the efficacy of treatments for a global honey bee pathogen - the Varroa mite.

The western honey bee Apis mellifera is the world's most important managed pollinator. However, globally honey bees have been facing increasing colony losses due to a combination of stress factors. Foremost among these is the invasive mite Varroa destructor, which is the pathogen most commonly linked to colony losses. Despite intensive research focus on this problem, V. destructor management remains extremely challenging, with no definitive treatment approach. A variety of synthetic chemical, agriculturally organic chemical, biological, and physical treatments have been trialled and used in V. destructor management, each with benefits and drawbacks. Here, we carried out a first systematic meta-analysis of the comparative effectiveness of V. destructor treatment methods. We incorporated data from 138 studies from 30 countries, across five continents and found that overall, synthetic chemicals show high effectiveness as a treatment due to their ability to suppress the V. destructor mite. In our analyses of honey bee responses, there was some evidence that synthetic chemicals may have an overall negative impact on them, even while suppressing V. destructor. For improving honey bee health measures, biological treatment methods showed the most positive effect, but with a relatively low sample size. Our study highlights that there is a relative lack of studies on biological management methods, with far more focus in the literature on chemical treatments. We show that, until biological methods receive greater research attention, agriculturally organic methods likely provide the best current treatment option, because they are well studied, nearly as effective at suppressing V. destructor as synthetic chemicals, and less associated with negative impacts on honey bees. Varroa destructor remains a major threat to honey bees globally, with the last large V. destructor free zone (Australia) having now been invaded, emphasising the need to fill these knowledge gaps.

Historical Simulation Systematically Underestimates the Expected Shortfall

Expected Shortfall (ES) is a risk measure that is acquiring an increasingly relevant role in financial risk management. In contrast to Value-at-Risk (VaR), ES considers the severity of the potential losses and reflects the benefits of diversification. ES is often calculated using Historical Simulation (HS), i.e., using observed data without further processing into the formula for its calculation. This has advantages like being parameter-free and has been favored by some regulators. However, the usage of HS for calculating ES presents a potentially serious drawback: It strongly depends on the size of the sample of historical data, being typically reasonable sizes similar to the number of trading days in one year. Moreover, this relationship leads to systematic underestimation: the lower the sample size, the lower the ES tends to be. In this letter, we present examples of this phenomenon for representative stocks and bonds, illustrating how the values of the ES and their averages are affected by the number of chosen data points. In addition, we present a method to mitigate the errors in the ES due to a low sample size, which is suitable for both liquid and illiquid financial products. Our analysis is expected to provide financial practitioners with useful insights about the errors made using Historical Simulation in the calculation of the Expected Shortfall. This, together with the method that we propose to reduce the errors due to finite sample size, is expected to help avoid miscalculations of the actual risk of portfolios.

Professional self-actualisation of pharmacist in the United Arab Emirates: a pilot study.

This pilot study evaluated the professional self-actualisation (PSA) of pharmacists in the United Arab Emirates (UAE) across various practice settings. Our study was conducted in the UAE from February to May 2024 and targeted pharmacists in hospitals, community pharmacies, industry, and academia. A PSA questionnaire was developed using validated instruments and expert input, and included items on professional fulfilment (PF), societal acceptance (SA), work environment (WE), autonomy and professional opportunities (APO), involvement in professional advocacy (IPA), and the impact of work on personal relationships (IWPR). Sixty-eight responses were received from pharmacists working in the community, hospital, industry and academic sectors. No significant differences in self-actualisation were observed between genders. PF scores were consistent across age groups, and education level significantly impacted IPA scores, with MSc/PhD holders (mean = 3.6, SD = 0.7) scoring higher than Bachelor's degree holders (mean = 2.9, SD = 0.9; p = 0.008). Years of experience were significantly associated with SA scores (p = 0.046), with pharmacists having 5-10 years of experience (mean = 3.5, SD = 0.8) scoring higher than those with less than 5 years (mean = 3.1, SD = 0.9) or more than 10 years (mean = 2.9, SD = 0.7). PF showed a strong correlation with a supportive WE (r = 0.744), highlighting the crucial role of a positive work setting in professional self-actualisation. This study identified key factors affecting pharmacists' self-actualisation in the UAE, emphasising the importance of a supportive work environment, recognition, and professional development for job satisfaction. Despite limitations such as low sample size and underrepresentation of certain sectors, the findings provide a basis for future research and inform strategies to enhance work environments, policies, and pharmacists' professional satisfaction.

A collaborative network analysis for the interpretation of transcriptomics data in Huntington’s disease

Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenic mechanisms from multiple perspectives.We analyzed a Huntington’s disease transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in Huntington’s disease and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation.In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.

An effective heuristic for developing hybrid feature selection in high dimensional and low sample size datasets.

High-dimensional datasets with low sample sizes (HDLSS) are pivotal in the fields of biology and bioinformatics. One of core objective of HDLSS is to select most informative features and discarding redundant or irrelevant features. This is particularly crucial in bioinformatics, where accurate feature (gene) selection can lead to breakthroughs in drug development and provide insights into disease diagnostics. Despite its importance, identifying optimal features is still a significant challenge in HDLSS. To address this challenge, we propose an effective feature selection method that combines gradual permutation filtering with a heuristic tribrid search strategy, specifically tailored for HDLSS contexts. The proposed method considers inter-feature interactions and leverages feature rankings during the search process. In addition, a new performance metric for the HDLSS that evaluates both the number and quality of selected features is suggested. Through the comparison of the benchmark dataset with existing methods, the proposed method reduced the average number of selected features from 37.8 to 5.5 and improved the performance of the prediction model, based on the selected features, from 0.855 to 0.927. The proposed method effectively selects a small number of important features and achieves high prediction performance.

Integration of gene expression and DNA methylation data using MLA-GNN for liver cancer biomarker mining

The early symptoms of hepatocellular carcinoma patients are often subtle and easily overlooked. By the time patients exhibit noticeable symptoms, the disease has typically progressed to middle or late stages, missing optimal treatment opportunities. Therefore, discovering biomarkers is essential for elucidating their functions for the early diagnosis and prevention. In practical research, challenges such as high-dimensional features, low sample size, and the complexity of gene interactions impact the reliability of biomarker discovery and disease diagnosis when using single-omics approaches. To address these challenges, we thus propose, Multi-level attention graph neural network (MLA-GNN) model for analyzing integrated multi-omics data related to liver cancer. The proposed protocol are using feature selection strategy by removing the noise and redundant information from gene expression and DNA methylation data. Additionally, it employs the Cartesian product method to integrate multi-omics datasets. The study also analyzes gene interactions using WGCNA and identifies potential genes through the MLA-GNN model, offering innovative approaches to resolve these issues. Furthermore, this paper identifies FOXL2 as a promising liver cancer marker through gene ontology and survival analysis. Validation using box plots showed that the expression of the gene FOXL2 was higher in patients with hepatocellular carcinoma than in normal individuals. The drug sensitivity correlation and molecular docking results of FOXL2 with the liver cancer-targeting agent lenvatinib emphasized its potential role in hepatocellular carcinoma treatment and highlighted the importance of FOXL2 in hepatocellular carcinoma treatment.

The efficacy and feasibility of an immersive virtual reality game to train spatial attention orientation after stroke: A stage 2 report.

Spatial neglect is a post-stroke attention deficit for which there is no evidence-based intervention. Immersive virtual reality (IVR) may increase treatment efficacy, as it allows to train spatial attention in a rich environment. This study evaluated the efficacy and feasibility of an IVR patient-tailored training (HEMIRehApp). Using a cross-over design, an active (spatially biased) and placebo (spatially unbiased) IVR intervention were compared. We aimed to recruit 8 per-protocol left-sided neglect patients. The primary outcome was response times on the Posner cueing task. To evaluate feasibility, we documented the number of recruited patients, cybersickness and patients' experience with HEMIRehApp. After 2 years of recruitment, we were able to enrol 6 patients, of whom 2 completed the full protocol. The target sample size was not feasible due to a lower than expected prevalence of left-sided neglect and a higher than expected drop-out rate. The planned group-level analysis was therefore replaced by a single-case analysis. The results in the 2 per-protocol cases suggest a superior effect of spatially biased IVR training than unbiased IVR training inside IVR. IVR training was feasible as all 6 enrolled patients were able to complete 10 IVR training sessions, but the cross-over protocol itself was unfeasible. While the low sample size prevented us from conclusively evaluating the efficacy of HEMIRehApp, our preliminary single-case results suggest that neglect patients were able to improve attentional orientation towards eccentric target locations in IVR. Follow-up studies are needed to further validate these findings.

Sampling for disease surveillance: assessing effects on blue‐winged teal survival and recovery

AbstractOutbreaks of highly pathogenic avian influenza virus in wild animals highlight the need for disease surveillance in wild birds to improve our understanding of their role as reservoirs and dispersers, and potential threats to domestic poultry and wild bird populations. Surveillance for avian influenza varies in its approach, objectives, and coordination with other monitoring efforts. For waterfowl, a common host to avian influenza viruses, banding represents a concerted effort of capturing and marking thousands of individuals annually to estimate survival and harvest rates, but users of these data have generally taken a conservative approach to remove any banded birds from analyses that had a sample taken for disease surveillance during capture. We tested for differences in survival and encounter probabilities of blue‐winged teal (Spatula discors) marked (n = 21,702 teal) and sampled for disease surveillance (n = 4,216) during the nonbreeding season in Louisiana, USA, from 2016 to 2023. Although we found no consistent effect of collecting biological samples on survival probability, including an additional test showing no detectable effects of sampling for disease surveillance with oropharyngeal and cloacal swabs versus sampling with swabs and a syringe‐drawn blood sample, wide 95% credible intervals on the posterior survival estimates (mean 0.36 difference between upper and lower values across all year‐sex‐sampling groups; 0.44 for sampling type groups) indicated low statistical power to detect an effect. Seber recovery probability during the first interval following sampling was lower among birds sampled using swabs only, but we assume this stems from low sample sizes rather than an effect of collecting biological samples. Because recovery probabilities can vary as a function of individual covariates, we also examined direct recovery probabilities and observed no meaningful effect of disease surveillance sampling type but strong effects of capture date, suggesting the effect on Seber recovery probability may have been due to heterogeneity in exposure to natural and harvest mortality risks. Although we suggest that aligning disease surveillance sample collection efforts with landscape‐scale waterfowl banding efforts may have little effect on observed demographic rates, additional studies with larger sample sizes are likely needed to provide the statistical power necessary to formally conclude no effect of biological sampling on survival probabilities.

Patient Persistence to OnabotulinumtoxinA Treatment for Overactive Bladder Using a Reduced Injection-Site Paradigm: A Retrospective Chart Review Study.

OnabotulinumtoxinA (onabotA) is an approved treatment for overactive bladder (OAB). This chart review study aims to determine treatment persistence in patients receiving onabotA (100 U) via a reduced injection-site paradigm distributed across ≤ 3 injection sites. This study was a single site, noninterventional, retrospective chart review evaluating adult female OAB patients refractory to behavioral modification and pharmacotherapy before receiving ≥ 1 treatment with onabotA (100 U) via 1-3 injections between July 2017 and June 2021. Patients with neurologic OAB, predominance of stress incontinence, or who expired during the study were excluded. Baseline demographics, treatment patterns, treatment persistence, treatment intervals, lidocaine pretreatment, patient-reported treatment response, and adverse urological events were documented and evaluated. Persistence was defined as the percent of patients receiving ≥ 3 treatments during the study period via three or fewer injections. Continuous variables were summarized with sample size, mean (standard deviation [SD]), and median (1st and 3rd quartiles); categorical variables were calculated as frequencies and percentages. Of the 90 patients included in this study, 55 (61.1%) were persistent to treatment with onabotA for OAB, completing 3 treatments by the end of the data collection period. Urinary tract infection (UTI) was reported after 18/370 (4.9%) treatments. Of 90 patients,15 (16.7%) reported UTI after any treatment, and none required clean intermittent catheterization. When onabotA was administered via a reduced injection-site paradigm, 61.1% of patients were persistent to OAB treatment. Given the limited pool of patients included in this study and relatively low sample sizes at later timepoints, results may not be generalizable. No new safety signals were identified using the reduced injection-site paradigm. Due to the nature of this study, no clinical trial registration was required.

Comparison of the power and type 1 error of total score models for drug effect detection in clinical trials

Composite scale data consists of numerous categorical questions/items that are often summed as a total score and are commonly utilized as primary endpoints in clinical trials. These endpoints are conceptually discrete and constrained by nature. Item response theory (IRT) is a powerful approach for detecting drug effects in composite scale data from clinical trials, but estimating all parameters requires a large sample size and all item information, which may not be available. Therefore, total score models are often utilized. The most popular total score models are continuous variable (CV) models, but this strategy establishes assumptions that go against the integer nature, and typically also the bounded nature, of data. Bounded integer (BI) and Coarsened grid (CG) models respect the nature of the data. However, their power to detect drug effects has not been as thoroughly studied in clinical trials. When an IRT model is accessible, IRT-informed models (I-BI and I-CV) are promising methods in which the mean and variability of the total score at any position are extracted from the existing IRT model. In this study, total score data were simulated from the MDS-UPDRS motor subscale. Then, the power, type 1 error, and treatment effect bias of six total score models for detecting drug effects in clinical trials were explored. Further, it was investigated how the power, type 1 of error, and treatment effect bias for the I-BI and I-CV models were affected by mis-specified item information from the IRT model. The I-BI model demonstrated the highest statistical power, maintained an acceptable Type I error rate, and exhibited minimal bias, approaching zero. Following that, the I-CV, BI, and CG with Czado transformation (CG_Czado) models provided the maximum power. However, the CG_Czado model had inflated type 1 error under low sample size scenarios in each arm of clinical trials. The CG model among total score models displayed the lowest power and the most inflated type 1 error. Therefore, the results favor the I-BI model when an IRT model is available; otherwise, the BI model.

MSR65 Can Low Effective Sample Size in Matching-Adjusted Indirect Comparisons (MAICS) Lead to Bias? Findings From a Simulation Study

MSR65 Can Low Effective Sample Size in Matching-Adjusted Indirect Comparisons (MAICS) Lead to Bias? Findings From a Simulation Study

Identifying Customer Satisfaction Characteristics with the Kano Model for the Agile Development of Video Games

Purpose: This study aims to use the Kano Model to identify critical attributes that can be used as features in video games developed using Agile software development. Methodology/Approach: Attributes were identified from the literature review and then selected for a survey given to university participants. Survey results were then analysed using the Kano Model table and a scatter plot. The survey identified respondents' preferences in video games. The survey responses were reanalysed using stratification by video game type. Findings: No one-dimensional attribute was found that would be critical to video game customers. Only a limited number of attractive attributes were identified from the aggregated data. Research Limitation/Implication: The analysis by type of video games had low sample sizes. Additionally, people from outside the target group responded to the survey. Originality/Value of paper: This paper identifies attributes to prioritise when developing a product and demonstrates the need to consider market segmentation when using the Kano Model.

Evolution of Self-reported Neuropsychiatric Symptoms After Switching from Dolutegravir/Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide: Results from the Randomized DOBINeuro Trial.

Central nervous system adverse events (AE) have been a cause of discontinuation of dolutegravir-containing therapy, especially in combination with abacavir. The main aim of the study was to evaluate whether the switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was associated with a reduction in severity and incidence of neuropsychiatric symptoms compared to continued dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). DOBINeuro is a randomized trial enrolling people living with HIV (PLWH) treated with DTG/ABC/3TC for > 6months and with HIV-RNA < 50 cps/ml for > 12months. At baseline, PLWH are randomized to continue DTG/ABC/3TC or switch to BIC/FTC/TAF. The original sample size was 50 PLWH per arm, but the enrollment was prematurely stopped due to a delayed recruitment process. Neuropsychiatric symptoms were evaluated by the self-report Symptom Checklist (SCL)-90-R and the Mini-International Neuropsychiatric Interview Plus. A total of 41 PLWH were enrolled and underwent randomization: 20 were randomized to continue DTG/ABC/3TC and 21 to switch to BIC/FTC/TAF. At baseline, clinical and laboratory characteristics were homogeneous in the two arms. Switching from DTG/ABC/3TC to BIC/FTC/TAF in virologically suppressed PLWH was associated with an improvement in sleep disorders but not in any other neuropsychiatric symptom. Although limited by a low sample size, this study suggests neuropsychiatric tolerability may improve when switching virologically suppressed PLWH from DTG to BIC-based strategies.

Electroacupuncture versus 5-HT4 receptor agonist for functional constipation: A systematic review and meta-analysis of randomized controlled trials.

Functional constipation (FC) has been found as a chronic gastrointestinal disease that is commonly diagnosed in patients. However, patients have a low satisfaction level with the treatment of constipation drugs (e.g., 5-HT4 agonists). A meta-analysis was performed to compare the efficacy and safety between electroacupuncture and 5-HT4 agonists. The included study were randomized controlled trials (RCTs), in which EA was used in the experimental group and 5-HT4 receptor agonist was used in the control group. Four English databases (PubMed, Cochrane Library, Web of Science, Embase) and 4 Chinese databases (China National Knowledge Infrastructure, CBM, WanFang, VIP) were searched. Relevant studies retrieved were published before September 30, 2024. The risk of bias was assessed by tool of Cochrane and GRADEpro. The Review Manager 5.4 was used for analyzing Data analysis, and Endnote X9 for screening studies. In this paper, we included 12 studies, involving 1473 participants. We found that EA significantly improved patient assessment of cab quality of life questionnaire (PAC-QOL) (MD = -0.52, P = .03), self-rating anxiety scale (SAS) (MD = -3.00, P < .00001) and self-rating depression scale (SDS) (MD = -4.13, P < .00001) compared with 5-HT4 receptor agonists. In addition, we failed to identify any significant difference in Stool consistency, the number of weekly complete spontaneous bowel movements and weekly spontaneous bowel movements (SBMs) between the 2 groups. EA has been indicated to be better than 5-HT4 receptor agonists since it can more effectively improve FC patients' life quality and mental state without an increased risk of adverse even. However, the previous evidence is characterized by low quality and small sample size, which should be further confirmed by high-quality and large-sample multicenter RCTs.

Gender-affirming hormone therapy: effects on cardiovascular risk and vascular function.

Gender-affirming hormone therapy (GAHT) is used in individuals with gender identity dysphoria to align an individual's secondary sexual characteristics with their affirmed gender. We conducted a systematic review of the literature to explore the mechanisms regarding the effects of GAHT on the vasculature. A literature search using PUBMED, Embase, Scopus and Lilacs was performed using search terms for GAHT, cardiovascular disease (CVD) risk and transgender. Studies were screened by two independent reviewers. Comparison to a cohort of transgender individuals naïve or prior to GAHT or a cisgender population was required. Quality assessment was done using the relevant Critical Skills Appraisal Programme checklists. Out of 2,564 potentially eligible studies, 69 studies met the inclusion criteria. Studies provided evidence of beneficial changes in CVD risk profile including reduced haemoglobin and pro-inflammatory markers, and atheroprotective changes in lipids in transgender women. In transgender men there was evidence of negative changes in CVD risk profile including atherogenic changes in lipids and increased haemoglobin, arterial stiffness, and pro-inflammatory markers. There is a paucity of research across non-traditional measures of CVD risk which in combination with heterogeneous study design, loss of follow-up, low sample sizes and lack of diversity in age and ethnicity requires the results to be interpreted with caution. More evidence is required to elucidate the mechanisms behind the increased risk of CVD in the transgender population and determine if GAHT is a contributing factor.

P066 Long-term outcomes from home invasive mechanical ventilation in Queensland

Abstract Home invasive mechanical ventilation (HIMV) is an uncommon but life-sustaining therapy for patients with chronic respiratory failure. However, the published literature on patient outcomes is inconsistent, reflecting varied practices. Moreover, local Australian data and detailed therapy outcomes are scarce. A retrospective review of patients treated with HIMV at a single tertiary centre between 01/01/2005 and 18/05/2024 was conducted. The primary outcome was the time from HIMV initiation to cessation or death. Secondary outcomes included diagnostic group, cause of death, number of hospitalisations and length of stay. Patient demographics were recorded. 31 patients were identified, with 26 meeting the inclusion criteria. The median age at injury was 35 years (9-77), with n=15 (57) male. Diagnostic groups included 13 (50%) spinal cord injuries, 4 (15%) brain injuries, 2 (8%) restrictive thoracic, 5 (19%) neuromuscular including 2 motor neuron disease and 2 (8%) other conditions. The mean survival on HIMV therapy was 19.6 years (95th CI 13.8-25.4). There was no significant difference in survival between patients with or without spinal cord injuries. Cause of death was predominantly respiratory failure (36%) and cardiovascular disease (27%). Median hospital encounters per patient-year on HIMV included 1.7 emergency department presentations, 1.4 hospital admissions, and 8.1 days of hospital stay. This study reported the longest mean survival on HIMV compared with international datasets. This may be due to low sample size, younger population, lower proportions of diagnostic groups with known poorer prognoses and heterogenous prior research.

Fine-scale behaviour and population estimates of endangered sooty albatross suggest low exposure (while not excluding high sensitivity) to bycatch

Recent developments in assessing species-specific seabird bycatch risks have demonstrated that fine-scale approaches are essential tools to quantify interactions with fishing vessels and to understand attraction and attendance behaviours. Matching boat movement with bird tracking data specifically allows us to investigate seabird-fisheries interactions for cryptic species for which on-board information is critically lacking. The sooty albatross Phoebetria fusca overlaps with fisheries throughout its range and is known to be vulnerable to incidental bycatch. Combining radar detectors, GPS and behavioural data from individuals from the Crozet Islands and boat locations during the incubation period, we investigated interactions of sooty albatrosses with fisheries in the southern Indian Ocean. Individuals foraged mostly in sub-tropical international waters, where they only encountered a small number of boats, all reporting to the Automatic Identification System (AIS). The low interaction rate during this period may suggest that sooty albatrosses are not strongly attracted to fishing vessels, and that attraction rates may vary between populations. However, this result should be interpreted with caution due to the low sample size and fishing effort during the study period, as these observations may conceal a higher bycatch risk during intense fishing effort and/or energetically demanding periods. The conservation status of this species requires further data to be collected throughout the annual cycle to provide an accurate assessment of the threat.