APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings.
CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
PATIENTS AND METHODS: Semi-structured online interviews comprised of six focus group discussions and five individual interviews were performed with 26 breast cancer patients. The interviews were recorded, transcribed, and analyzed using the reflexive thematic analysis approach.
RESULTS: Four main themes were derived: (1) positive treatment outcomes; (2) the negative impact of treatment-related side effects on quality of life; (3) treatment accessibility, availability, and timeliness; (4) cost of treatment. Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. Additionally, patients favored treatments with minimal side effects that had minimal impact on their quality of life. There was a notable preference for treatments that were easily accessible and available in a timely manner. However, patients faced challenging decisions in balancing the costs of treatments with their benefits, leading to a consistent preference for treatments supported by government funding or medical insurance to alleviate financial burdens.
CONCLUSION: Our study reveals that breast cancer patients in New Zealand have different perceptions and preferences regarding cancer treatment. Patients frequently find themselves making trade-offs among various attributes of a treatment, aligning these decisions with their personal values and beliefs. By considering these preferences and trade-offs in future studies that measure patient preferences, healthcare professionals can enhance their support for patients in making informed choices that align with their values and priorities. Additionally, healthcare policymakers can develop patient-centered policies that cater to the unique needs and preferences of breast cancer patients.
METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs.
ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.
METHODS: A genome-wide association study was conducted using breast cancer mutation status of TP53 and PIK3CA and functional mutation categories including TP53 gain of function (GOF) and loss of function mutations and PIK3CA activating/hotspot mutations. The discovery analysis consisted of 2850 European ancestry women from three datasets. Germline variants showing evidence of association with somatic mutations were selected for validation analyses based on predicted function, allele frequency, and proximity to known cancer genes or risk loci. Candidate variants were assessed for association with mutation status in a multi-ancestry validation study, a Malaysian study, and a study of African American/Black women with TNBC.
RESULTS: The discovery Germline x Mutation (GxM) association study found five variants associated with one or more TP53 phenotypes with P values <1×10-6, 33 variants associated with one or more TP53 phenotypes with P values <1×10-5, and 44 variants associated with one or more PIK3CA phenotypes with P values <1×10-5. In the multi-ancestry and Malaysian validation studies, germline ESR1 locus variant, rs9383938, was associated with the presence of TP53 mutations overall (P values 6.8×10-5 and 9.8×10-8, respectively) and TP53 GOF mutations (P value 8.4×10-6). Multiple variants showed suggestive evidence of association with PIK3CA mutation status in the validation studies, but none were significant after correction for multiple comparisons.
CONCLUSIONS: We found evidence that germline variants were associated with TP53 and PIK3CA mutation status in breast cancers. Variants near the estrogen receptor alpha gene, ESR1, were significantly associated with overall TP53 mutations and GOF mutations. Larger multi-ancestry studies are needed to confirm these findings and determine if these variants contribute to ancestry-specific differences in mutation frequency.
OBJECTIVE: To evaluate the performance of the model and control strategies, benchmarking simulations are performed using the PlatEMO platform.
METHODS: The Pure Multi-objective Optimal Control Problem (PMOCP) and the Hybrid Multi-objective Optimal Control Problem (HMOCP) are two different forms of optimal control problems that are solved using revolutionary metaheuristic optimisation algorithms. The utilization of the Hypervolume (HV) performance indicator allows for the comparison of various metaheuristic optimization algorithms in their efficacy for solving the PMOCP and HMOCP.
RESULTS: Results indicate that the MOPSO algorithm excels in solving the HMOCP, with M-MOPSO outperforming for PMOCP in HV analysis.
CONCLUSION: Despite not directly addressing immediate clinical concerns, these findings indicates that the stability shifts at critical thresholds may impact treatment efficacy.
OBJECTIVE: The present study aims to provide insights into the prevalence of anxiety disorders and explore the correlations between anxiety symptoms, sleep, and memory during the COVID-19 pandemic.
METHODS: To conduct a cross-sectional study, 42 older adult participants between the ages of sixty to seventy years were chosen and the procedure was explained.Data were gathered by giving instructions on how to complete the self-reported Generalized Anxiety Disorder Assessment -7 (GAD-7), the Epworth Sleepiness Scale, and the revised Everyday Memory Questionnaire.
RESULTS: A total of 36 out of 42 participants (85.71%) experienced moderate to severe anxiety. Anxiety and sleep had a correlation of 0.8, while anxiety and memory had a correlation of 0.87 with a positive EMQ-R relationship. Moreover, there was a statistically significant association between sleep and memory, with a positive correlation of 0.73.
CONCLUSION: The study concludes that, there is a substantial prevalence of anxiety accompanied by notable insomnia and memory problems in elderly security officers. Our findings indicate a clear relationship between sleep disturbances, memory issues, and most prevalent anxiety symptoms. These results emphasize the importance of incorporating mental health assessments and addressing an effective treatment for anxiety.
OBJECTIVE: This study examines how risk perceptions of COVID-19, employee well-being, workplace health and safety training, safety motivation and safety related stigma impact safety compliance behavior in times COVID-19 pandemic.
METHODS: A self-administered questionnaire was disseminated to healthcare workers. In all, 344 acceptable questionnaires were derived for further analysis.
RESULTS: The results revealed that the risk perception of COVID-19 and employee well-being has no significant relationship with safety compliance behavior. Similarly, safety related stigma also has no moderating effect on safety motivation and safety compliance behavior. However, workplace health and safety training and safety motivation have significant relationships with safety compliance behavior.
CONCLUSION: This study contributes to the literature by illuminating on the importance of organizational, individual, social factors and how they can interact with safety compliance behaviour. Additionally, knowing the unique function of safety related stigma in building safety compliance behaviour may help guide future efforts and training initiatives to enhance workplace safety.