Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France.

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

Addressing methodological concerns in omega-3 trial for bipolar disorder relapse prevention.

Our response addresses concerns raised about our pilot trial on omega-3 for bipolar disorder. We clarify randomization procedures, highlight the benefits of eicosapentaenoic-predominant formulations for a specific bipolar patients subgroup, and justify the use of Kaplan-Meier analysis despite limitations. We acknowledge analytical challenges due to strict inclusion criteria and encourage future research on specific bipolar subtypes and larger-scale trials for robust validation.

Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations.

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

Real-world evidence in the reassessment of oncology therapies: payer perceptions from five countries.

Aim: This study explored the perceived value of real-world evidence (RWE) in the reassessment of oncology therapies by collecting the perspectives of health technology assessment/payer decision-makers. Materials & methods: A web-based survey was conducted using the Market Access Transformation Rapid Payer Response online portal. 30 participants from France, Germany, Spain, the UK and the USA were recruited based on their expertise. Results: Participants agreed that the most common uses of RWE are to confirm efficacy and safety results from randomized controlled trials and to reevaluate the projected utilization of an oncology therapy. We found variability in other reported uses of RWE. Conclusion: The organizations developing RWE should ensure that their plans recognize the heterogeneity in payer perceptions.

Mothering and mother-child interactions in the unaffected siblings of autistic children.

AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children. METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting. RESULTS: Regardless of the child's age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics. INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child's behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.

Patient experience and unmet needs in high-risk nonmuscle-invasive bladder cancer: Insights from qualitative interviews and a cross-sectional survey.

OBJECTIVES: To evaluate patient experience, unmet needs, and burden among patients with high-risk nonmuscle-invasive bladder cancer (HR-NMIBC) treated with Bacillus Calmette-Guérin (BCG). METHODS: This cross-sectional study included HR-NMIBC patients who received BCG treatment in the past 3 years. The study, preceded by a focused literature review, was conducted in 2 phases: 1) qualitative interviews with 32 patients in the United States (US), France, Germany, and United Kingdom (UK) and 2) quantitative survey of 150 patients in the US. Both phases of the study assessed patient characteristics, treatment history, experience, and perceptions, as well as side effects, pain, discomfort, and time burden associated with BCG treatment. The quantitative survey included additional items related to BCG treatment satisfaction, health-related quality of life (HRQoL), productivity, and healthcare resource utilization. Descriptive statistics and bivariate subgroup comparisons were reported. RESULTS: All patients in both study phases received transurethral resection of the bladder tumor (TURBT). Nearly all patients reported keeping their bladder/avoiding radical cystectomy (RC) was important (99%). Results from the quantitative survey reported a substantial impact to cancer-specific HRQoL of patients, with lower mean scores on physical (64.7), social (62.8), and role functioning (56.7) as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30). Most patients (69%) were satisfied overall with BCG treatment, although satisfaction declined with increased number of side effects, higher numbers of BCG administrations, and greater discomfort (all P < 0.05). CONCLUSIONS: Most HR-NMIBC patients were satisfied overall with BCG treatment. Approximately half of the patients had stopped BCG treatment, notably, most during the induction phase, suggesting nonadherence to guidelines which recommend maintenance treatment after induction. Future treatments should focus on delaying or avoiding recurrence and cystectomy while reducing patient discomfort and discontinuation prior to completing the recommended course of treatment.

Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Training in neuropsychiatry: views of early career psychiatrists from across the world.

BACKGROUND: Training and practice in neuropsychiatry varies across the world. However, little is known about the experiences and opinions of early career psychiatrists (ECPs) across different countries regarding neuropsychiatry. AIMS AND METHOD: To investigate neuropsychiatry training experiences, practices and opinions among ECPs across different countries. An online survey was distributed to ECPs in 35 countries across the world. RESULTS: A total of 522 participants took part in this study. Responses show that neuropsychiatry is integrated to a variable extent in psychiatric training curricula across the world. Most respondents were not aware of the existence of neuropsychiatric training or of neuropsychiatric units. Most agreed that training in neuropsychiatry should be done during or after the psychiatry training period. Lack of interest among specialty societies, lack of time during training, and political and economic reasons are regarded as the main barriers. CLINICAL IMPLICATIONS: These findings call for an improvement in the extent and in the quality of neuropsychiatry training across the world.

Cost-effectiveness analysis for avelumab first-line maintenance treatment of advanced urothelial carcinoma in Scotland.

Aim: The cost-effectiveness of avelumab first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma in Scotland was assessed. Materials & methods: A partitioned survival model was developed comparing avelumab plus best supportive care (BSC) versus BSC alone, incorporating JAVELIN Bladder 100 trial data, costs from national databases and published literature and clinical expert validation of assumptions. Incremental cost-effectiveness ratio (ICER) was estimated using lifetime costs and quality-adjusted life-years (QALY). Results: Avelumab plus BSC had incremental costs of £9446 and a QALY gain of 0.63, leading to a base-case (deterministic) ICER of £15,046 per QALY gained, supported by robust sensitivity analyses. Conclusion: Avelumab first-line maintenance is likely to be a cost-effective treatment for locally advanced or metastatic urothelial carcinoma in Scotland.

What is this article about? This study looked at the costs of avelumab when given as maintenance treatment for people in Scotland with advanced urothelial carcinoma, compared with the longer survival and other benefits that it provides. How was this done? Researchers estimated the costs and treatment benefits expected with avelumab using data from a clinical trial called JAVELIN Bladder 100, national databases, data from previously published studies and expert opinions. What were the results? Costs associated with using avelumab maintenance treatment for people with advanced urothelial carcinoma in Scotland were considered to be acceptable based on the benefits it provides. What do the results of the study mean? These results support the use of avelumab first-line maintenance as a standard treatment for people with advanced urothelial carcinoma in Scotland.

Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Reliability, validity, and change thresholds of the NCCN/FACT Bladder Symptom Index (NFBlSI-18) in patients with advanced urothelial cancer.

BACKGROUND: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a bladder cancer-specific instrument. We aimed to psychometrically evaluate the reliability and validity of NFBlSI-18 and estimate change thresholds for total, disease-related symptoms-physical (DRS-P), DRS-emotional (DRS-E), and function/well-being (F/WB) scales in patients with locally advanced/metastatic urothelial cancer (la/mUC). METHODS: JAVELIN Bladder 100 trial data were analyzed. Anchors to evaluate validity included: 5-level EuroQoL-5D utility index (EQ-5D-5L UI), visual analog scale (VAS), Eastern Cooperative Oncology Group (ECOG) performance status, and number of symptoms. Responsiveness to change was tested by anchoring to time to tumor progression (TTP), best overall response (BOR), and differences in means between ECOG categories to estimate meaningful between-group differences. Meaningful within-group change thresholds were estimated using receiver operating characteristic curve analysis, anchoring to change in EQ-5D-5L UI. Significant within-individual patient change thresholds were estimated with reliable and likely change indexes. RESULTS: Correlations with EQ-5D-5L UI and VAS ranged from 0.53 to 0.73. Standardized effect sizes were >0.20. Compared with patients with TTP of ≥6 months, patients with TTP of >0-2 and 3-5 months had larger declines; results for BOR were similar. Thresholds (points) for meaningful between-group differences were: total, 6-11; DRS-P, 3-6; and DRS-E and F/WB, 1. Thresholds (points) for meaningful within-group worsening were: total, 4; and DRS-P, 3, and for significant individual change they were: total, 3-9; DRS-P, 2-6; DRS-E, 1-3; and F/WB, 2-4. CONCLUSIONS: NFBlSI-18 exhibited evidence of reliability, validity, and responsiveness to assess quality of life in studies of la/mUC, and change thresholds are established for future studies. PLAIN LANGUAGE SUMMARY: The NCCN/FACT Bladder Symptom Index-18 (NFBlSI-18) is a questionnaire used to assess quality of life for people with advanced bladder cancer. People with advanced bladder cancer who took part in the JAVELIN Bladder 100 study completed the NFBlSI-18 when they joined the study and after each treatment with avelumab maintenance or best supportive care. This study showed that NFBlSI-18 is suitable for capturing bladder cancer symptoms and is able to detect important changes in a person's quality of life over time. This study also provides thresholds for changes in NFBlSI-18 scores, which will be useful for future studies.

Real-World Analysis of Treatment Patterns and Platinum-Based Treatment Eligibility of Patients With Metastatic Urothelial Cancer in 5 European Countries.

INTRODUCTION: The global treatment landscape for metastatic urothelial cancer (mUC) is evolving, with the recent approval of several new therapeutics. To enable informed treatment decisions, a need exists to understand both treatment patterns and how physicians determine platinum-based treatment eligibility status. This study investigated physicians' current approaches to first-line (1L) chemotherapy, treatment patterns, and assessment of platinum-based treatment eligibility of patients with mUC in real-world clinical practice. PATIENTS AND METHODS: Data were derived from the Adelphi mUC Disease Specific Programme™, a large, independent, multinational, cross-sectional survey of physicians and their consulting patients with mUC presenting in a real-world clinical setting, conducted in France, Germany, Italy, Spain, and the United Kingdom between November 2020 and April 2021. Physicians completed record forms for their next 8 consecutively consulting patients (≤3 1L, ≤2 second-line, and ≤3 third-line) with a physician-confirmed diagnosis of mUC, reporting data on demographics, clinical characteristics, eligibility for platinum-based chemotherapy, and treatments received. RESULTS: Overall, 232 physicians provided data for 1922 patients. Renal function impairment (72%), Eastern Cooperative Oncology Group performance status (59%), and age (38%) were the most commonly reported criteria physicians used to determine eligibility for platinum-based chemotherapy. At 1L, 82% of patients received platinum-based chemotherapy (cisplatin, 51%; carboplatin, 31%) and 10% received immune checkpoint inhibitor (ICI) therapy. At second-line, 12% received platinum-based chemotherapy, 63% ICI therapy, and 21% non-platinum-based chemotherapy. At third-line, 4% received platinum-based chemotherapy, 41% best supportive care only, and 36% other non-platinum-based chemotherapy. CONCLUSIONS: The results of this real-world study indicate that in accordance with European guidelines, the majority of patients with mUC received standard-of-care 1L platinum-based chemotherapy and use of ICIs was limited. Future research should assess how physicians' perceptions toward determining platinum eligibility status evolve with newer guideline recommendations and the introduction of new therapy options for mUC.

Building knowledge using a novel web-based intervention to promote HPV vaccination in a diverse, low-income population.

OBJECTIVES: HPV vaccination rates remain suboptimal despite proven efficacy. Data suggest misconceptions or lack of knowledge are leading barriers. Our study aimed to develop and pilot a novel interactive education resource designed to educate parents and patients about HPV vaccines. METHODS: This is a prospective pilot study conducted in an urban teaching hospital pediatric clinic. The Patient Activated Learning System (PALS) intervention included 3 web-based videos with HPV vaccine-related educational content. Participants were parents of adolescent patients, aged 11-17 years, and young adult patients, aged 18-26 years. Enrolled participants completed an HPV vaccine knowledge survey before and after watching PALS; paired scores were evaluated. Acceptability and participant-reported impact of PALS modules were measured via Likert-scale surveys. RESULTS: 132 individuals were approached; 101 (76%) enrolled and completed the study. Participants self-identified as Hispanic (50%), non-Hispanic Black (23%), non-Hispanic White (7%), Asian (6%), American/Alaskan/Hawaiian Native or Pacific Islander (5%). Half reported earning ≤$40,000 annually; 57% had only a high school education. Post-intervention knowledge scores were increased compared to baseline (9.87/27 points vs 17.53/27 points, p < 0.01). PALS modules were reported as enjoyable to use and understandable (89% and 93%, respectively), and improved participants' understanding of the importance of HPV vaccination (90%). Of the 18 patients unvaccinated at baseline, 39% received 1 shot of the HPV vaccine within one month. CONCLUSION: The PALS HPV vaccine educational intervention was feasible, acceptable, and improved knowledge among a diverse, underserved population. Our intervention may positively influence HPV vaccination rates, with potential to overcome HPV vaccine hesitancy.

Roles of Omega-3 Polyunsaturated Fatty Acids in Managing Cognitive Impairment in Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders.

BACKGROUND: The aim of our study was to evaluate the expression of the CASP3 gene at both mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the pathogenesis of depression; METHODS: A total of 290 subjects, including 190 depressed patients and 100 healthy controls, participated in the study. Socio-demographic and clinical data were collected, and the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Venous blood was collected and gene expression was evaluated using RT-PCR and ELISA at the mRNA and protein levels, respectively; RESULTS: The expression of the CASP3 gene was significantly lower in depressed patients compared to healthy controls at both the mRNA and protein levels. Additionally, a positive correlation was observed between CASP3 gene expression and disease duration as well as the number of depressive episodes; CONCLUSIONS: Further studies are needed to investigate the role of caspase 3 in depressive disorders.

Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.

The now and future of ChatGPT and GPT in psychiatry.

ChatGPT has sparked extensive discussions within the healthcare community since its November 2022 release. However, potential applications in the field of psychiatry have received limited attention. Deep learning has proven beneficial to psychiatry, and GPT is a powerful deep learning-based language model with immense potential for this field. Despite the convenience of ChatGPT, this advanced chatbot currently has limited practical applications in psychiatry. It may be used to support psychiatrists in routine tasks such as completing medical records, facilitating communications between clinicians and with patients, polishing academic writings and presentations, and programming and performing analyses for research. The current training and application of ChatGPT require using appropriate prompts to maximize appropriate outputs and minimize deleterious inaccuracies and phantom errors. Moreover, future GPT advances that incorporate empathy, emotion recognition, personality assessment, and detection of mental health warning signs are essential for its effective integration into psychiatric care. In the near future, developing a fully-automated psychotherapy system trained for expert communication (such as psychotherapy verbatim) is conceivable by building on foundational GPT technology. This dream system should integrate practical 'real world' inputs and friendly AI user and patient interfaces via clinically validated algorithms, voice comprehension/generation modules, and emotion discrimination algorithms based on facial expressions and physiological inputs from wearable devices. In addition to the technology challenges, we believe it is critical to establish generally accepted ethical standards for applying ChatGPT-related tools in all mental healthcare environments, including telemedicine and academic/training settings.

A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.