A Comprehensive Analysis of Litigation in Organ Transplantation for Allegations of Insufficient Policy Coverage, Discrimination and Malpractice.

Introduction: Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design: The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results: One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion: Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.

Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis.

INTRODUCTION: IgA nephropathy (IgAN) can cause end-stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT). METHODS: Retrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival. RESULTS: Compared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90, p < .010, 95% CI [1.169-3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665, p = .044, 95% CI [.447-.989]), graft failure (HR .758, p = .002, 95% CI [.633-.907]), and death (HR .619, p < .001, 95% CI [.490-.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs. CONCLUSION: In patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality.

Equivalence in Color-coded Duplex Sonography Parameters before Complex Microsurgery.

Background: Color-coded duplex sonography (CCDS) is a widely proposed noninvasive diagnostic tool in microsurgery. CCDS has been applied to lower extremity salvage cases to define appropriate blood flow velocity criteria for achieving arterial success in diabetic foot and complex microsurgery cases. This study aimed to compare the success ratio of free flaps when using CCDS versus cases where CCDS was not used. Methods: We included complex microsurgery cases from 2019 to 2021. These cases were subsequently categorized into two groups: group A consisted of cases where CCDS parameters were applied, whereas group B comprised cases where CCDS was not performed at all. Results: The study encompassed 14 cases (11 men and three women). The age range varied from 23 to 62 years, with an average age of 42. Using CCDS analysis and planning demonstrated improved outcomes in comparison with cases where CCDS was not performed, albeit without statistical significance (P = 0.064). Conclusions: The application of CCDS proves to be beneficial in the realm of microsurgery. Although not achieving statistical significance, our data imply that CCDS utilization holds promise for enhancing microsurgical procedures.

Moving psychiatric deinstitutionalisation forward: A scoping review of barriers and facilitators.

Psychiatric deinstitutionalisation (PDI) processes aim to transform long-term psychiatric care by closing or reducing psychiatric hospitals, reallocating beds, and establishing comprehensive community-based services for individuals with severe and persistent mental health difficulties. This scoping review explores the extensive literature on PDI, spanning decades, regions, socio-political contexts, and disciplines, to identify barriers and facilitators of PDI implementation, providing researchers and policymakers with a categorization of these factors. To identify barriers and facilitators, three electronic databases (Medline, CINAHL, and Sociological Abstracts) were searched, yielding 2250 references. After screening and reviewing, 52 studies were included in the final analysis. Thematic synthesis was utilized to categorize the identified factors, responding to the review question. The analysis revealed that barriers to PDI include inadequate planning, funding, and leadership, limited knowledge, competing interests, insufficient community-based alternatives, and resistance from the workforce, community, and family/caregivers. In contrast, facilitators encompass careful planning, financing and coordination, available research and evidence, strong and sustained advocacy, comprehensive community services, and a well-trained workforce engaged in the process. Exogenous factors, such as conflict and humanitarian disasters, can also play a role in PDI processes. Implementing PDI requires a multifaceted strategy, strong leadership, diverse stakeholder participation, and long-term political and financial support. Understanding local needs and forces is crucial, and studying PDI necessitates methodological flexibility and sensitivity to contextual variation. At the same time, based on the development of the review itself, we identify four limitations in the literature, concerning 'time', location', 'focus', and 'voice'. We call for a renewed research and advocacy agenda around this neglected aspect of contemporary global mental health policy is needed.

Creating Value in Non-Profit Sports Organizations: An Analysis of the DART Model and Its Performance Implications.

This study aims to analyze the impact of value creation and cocreation, as measured by the dialogue, access, risk assessment, and transparency (DART) model, on the performance of non-profit sports organizations (NPSOs). To assess this impact, the authors analyzed data collected from sports and administration managers of NPSOs, specifically Colombian amateur soccer clubs. The study used partial-least-squares structural-equation modeling (PLS-SEM) with constructs of the reflexive-formative type. The results indicate that value creation has a positive impact on the performance of NPSOs through the mediating effect of value cocreation. Despite the limitations of this study, including the limited research on the relationship between value creation and cocreation and NPSO performance in Colombia, the findings contribute to the understanding of the mediating effect of cocreation. The authors found that cocreation mainly affects the sport, customers/members, communication and image, finance, and organization dimensions of NPSOs in developing countries. This study draws attention to the potential benefits of cocreation for NPSOs and emphasizes the importance of creating value in this context. The study concludes that further studies on the constructs proposed in this research would help to understand the phenomenon of innovation and its impact on NPSOs. Overall, this study provides valuable insights for managers and policymakers in NPSOs-especially in developing countries-on the importance of value cocreation in improving their performance.

Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern.

Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.

Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy. The primary end point was MFS. Descriptive statistics are reported for this post hoc analysis. Results: In Spanish participants, darolutamide (n = 75) prolonged MFS versus placebo (n = 42): hazard ratio 0.345, 95% confidence interval 0.175-0.681. The incidence and type of treatment-emergent adverse events were comparable between treatment arms. Conclusion: For Spanish participants in ARAMIS, efficacy outcomes favored darolutamide versus placebo, with a similar safety profile, consistent with the overall ARAMIS population. Clinical Trials Registration: NCT02200614 (ClinicalTrials.gov).

Darolutamide is an oral treatment for a type of prostate cancer that has stopped responding to other treatments and is at risk of spreading to other parts of the body (termed "nonmetastatic castration-resistant prostate cancer" or "nmCRPC"). In the international ARAMIS study, patients treated with darolutamide lived longer without their cancer spreading than patients who were given placebo (sugar) pills. We wanted to know whether Spanish patients in ARAMIS had similar characteristics and treatment outcomes to other patients in the study. We found that the 75 Spanish patients who were treated with darolutamide had a significantly lower risk of their cancer spreading than the 42 Spanish patients who received placebo. The two groups of Spanish patients had similar side effects.

Increased CMV disease and "severe" BK viremia with belatacept vs. sirolimus three-drug maintenance immunosuppression.

OBJECTIVES: Belatacept may provide benefit in delayed graft function, but its association with infectious complications is understudied. We aim to assess the incidence of CMV and BK viremia in patients treated with sirolimus or belatacept as part of a three-drug immunosuppression regimen after kidney transplantation. MATERIALS AND METHODS: Kidney transplant recipients from 01/01/2015 to 10/01/2021 were retrospectively reviewed. Maintenance immunosuppression was either tacrolimus, mycophenolate and sirolimus (B0) or tacrolimus, mycophenolate, and belatacept (5.0 mg/kg monthly) (B1). Primary outcomes of interest were BK and CMV viremia which were followed until the end of the study period. Secondary outcomes included graft function (serum creatinine, eGFR) and acute rejection through 12 months. RESULTS: Belatacept was initiated in patients with a higher mean kidney donor profile index (B0:0.36 vs. B1:0.44, p = .02) with more delayed graft function (B0:6.1% vs. B1:26.1%, p < .001). Belatacept therapy was associated with more "severe" CMV viremia >25,000 copies/mL (B0:1.2% vs. B1:5.9%, p = .016) and CMV disease (B0:0.41% vs. B1:4.2%, p = .015). However, there was no difference in the overall incidence of CMV viremia >200 IU/mL (B0:9.4% vs. B1:13.5%, p = .28). There was no difference in the incidence of BK viremia >200 IU/mL (B0:29.7% vs. B1:31.1%, p = .78) or BK-associated nephropathy (B0:2.4% vs. B1:1.7%, p = .58), but belatacept was associated with "severe" BK viremia, defined as >10,000 IU/mL (B0:13.0% vs. B1:21.8%, p = .03). The mean serum Cr was significantly higher with belatacept therapy at 1-year follow up (B0:1.24 mg/dL vs. B1:1.43 mg/dL, p = .003). Biopsy-proven acute rejection (B0:1.2% vs. B1:2.6%, p = .35) and graft loss (B0:1.2% vs. B1:0.84%, p = .81) were comparable at 12 months. CONCLUSIONS: Belatacept therapy was associated with an increased risk of CMV disease and "severe" CMV and BK viremia. However, this regimen did not increase the overall incidence of infection and facilitated comparable acute rejection and graft loss at 12-month follow up.

Unintentional Injury Death Among Solid Organ Transplant Recipients: Trends and Risk Factors.

Unintentional injury death (UID) is a leading cause of mortality worldwide, and individuals with chronic diseases are at higher risk. Though organ transplant can improve the lives of those with chronic disease, these individuals remain in suboptimal physical and mental health after surgery that predisposes them to UID. To quantify the scale of UID among solid organ transplant recipients, we performed a retrospective analysis using United Network of Organ Sharing data from adults who underwent kidney, liver or pancreas transplant between 2000-2021. Our study aimed to identify risk factors for UID in this cohort by comparing basic patient, donor, and transplant characteristics of the groups (UID or all other cause death). The largest proportion of UID was seen in the kidney group (.8%), followed by liver (.7%) and then pancreas (.3%). Male sex was the most significant risk factor among kidney and liver recipients. Whites had a higher risk for UID relative to their non-White counterparts in the kidney and liver groups. In both groups, advancing age conferred a protective effect, whereas higher functional status was a risk factor. Our findings shed new light on a significant source of mortality within the transplant population.

Demographic inequities exist and influence transplant outcomes in liver transplantation for acute alcohol-associated hepatitis.

BACKGROUND: Liver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. METHODS: A retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. RESULTS: In comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or "other" race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). CONCLUSION: Our results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.

B cells as modulators of HPV+ oropharyngeal cancer in a preclinical model.

Among the different immune cells present within tumors, B cells also infiltrate human papillomavirus-positive (HPV+) oropharyngeal tumors. However, the role of B cells during programmed death-1 (PD-1) blockade in HPV+ oropharyngeal cancer needs to be better defined. By using the preclinical mouse model for HPV+ oropharyngeal cancer (named mEER), we characterized B cells within tumors and determined their functional role in vivo during PD-1 blockade. We determined that treatment naïve tongue-implanted tumors, which we have previously demonstrated to be sensitive to PD-1 blockade, contained high infiltration of CD8+ T cells and low infiltration of B cells whereas flank-implanted tumors, which are resistant to PD-1 blockade, contain a higher frequency of B cells compared to T cells. Moreover, B cell-deficient mice (µMt) and B cell-depleted mice showed a slower tumor growth rate compared to wild-type (WT) mice, and B cell deficiency increased CD8+ T cell infiltration in tumors. When we compared tongue tumor-bearing mice treated with anti-PD-1, we observed that tumors that responded to the therapy contained more T cells and B cells than the ones that did not respond. However, µMt mice treated with PD-1 blockade showed similar tumor growth rates to WT mice. Our data suggest that in untreated mice, B cells have a more pro-tumorigenic phenotype potentially affecting T cell infiltration in the tumors. In contrast, B cells are dispensable for PD-1 blockade efficacy. Mechanistic studies are needed to identify novel targets to promote the anti-tumorigenic function and/or suppress the immunosuppressive function of B cells in HPV+ oropharyngeal cancer.

Effect of probiotics on glucose levels and weight gain in mice exposed to low doses of malathion.

INTRODUCTION: Owing to its ability to reduce the toxicity of environmental pollutants that are risk factors for diabetes and obesity, the use of probiotic bacteria might aid the treatment of these diseases. OBJECTIVE: To determine the effects of chronic exposure to low-dose malathion on weight and glucose levels in mice, as well as to evaluate the protective role of a probiotic supplement. METHODS: Weight and serum glucose levels of four groups of mice (control, malathion-exposed [10 ppm], probiotics and malathion + probiotics) were determined every 10 days for 180 days. RESULTS: Malathion administration induced an increase in weight and glucose levels in the malathion group mice in comparison with the other groups. CONCLUSIONS: Consumption of food contaminated with malathion residues increases glucose levels and favors weight gain, while consumption of probiotics reduces the effects generated by residues in food.

INTRODUCCIÓN: Debido a su capacidad para reducir la toxicidad de contaminantes ambientales que constituyen factores de riesgo de diabetes y obesidad, el uso de bacterias probióticas podría ayudar al tratamiento de esas enfermedades. OBJETIVO: Determinar los efectos de la exposición crónica a malatión a dosis bajas sobre el peso y los niveles de glucosa de ratones, así como evaluar el papel protector de un suplemento probiótico. MÉTODOS: Cada 10 días se determinó el peso y la glucosa sérica de cuatro grupos de ratones (de control, expuestos a malatión (10 ppm), probióticos y malatión + probióticos) durante 180 días. RESULTADOS: La administración de malatión provocó un incremento del peso y los niveles de glucosa en los ratones del grupo con malatión comparados con los demás grupos. CONCLUSIONES: El consumo de alimentos contaminados con residuos de malatión aumenta los niveles de glucosa y favorece el incremento del peso; el consumo de probióticos disminuye los efectos generados por los residuos en los alimentos.

Efecto de los probióticos en los niveles de glucosa y el incremento de peso en ratones expuestos a dosis bajas de malatión / Effect of probiotics on glucose levels and weight gain in mice exposed to low doses of malathion

Resumen Introducción: Debido a su capacidad para reducir la toxicidad de contaminantes ambientales que constituyen factores de riesgo de diabetes y obesidad, el uso de bacterias probióticas podría ayudar al tratamiento de esas enfermedades. Objetivo: Determinar los efectos de la exposición crónica a malatión a dosis bajas sobre el peso y los niveles de glucosa de ratones, así como evaluar el papel protector de un suplemento probiótico. Métodos: Cada 10 días se determinó el peso y la glucosa sérica de cuatro grupos de ratones (de control, expuestos a malatión (10 ppm), probióticos y malatión + probióticos) durante 180 días. Resultados: La administración de malatión provocó un incremento del peso y los niveles de glucosa en los ratones del grupo con malatión comparados con los demás grupos. Conclusiones: El consumo de alimentos contaminados con residuos de malatión aumenta los niveles de glucosa y favorece el incremento del peso; el consumo de probióticos disminuye los efectos generados por los residuos en los alimentos.

Abstract Introduction: Owing to its ability to reduce the toxicity of environmental pollutants that are risk factors for diabetes and obesity, the use of probiotic bacteria might aid the treatment of these diseases. Objective: To determine the effects of chronic exposure to low-dose malathion on weight and glucose levels in mice, as well as to evaluate the protective role of a probiotic supplement. Methods: Weight and serum glucose levels of four groups of mice (control, malathion-exposed [10 ppm], probiotics and malathion + probiotics) were determined every 10 days for 180 days. Results: Malathion administration induced an increase in weight and glucose levels in the malathion group mice in comparison with the other groups. Conclusions: Consumption of food contaminated with malathion residues increases glucose levels and favors weight gain, while consumption of probiotics reduces the effects generated by residues in food.

Electronic Patient Portal Use After Kidney Transplant: A Single-Center Retrospective Study.

INTRODUCTION: Online patient portals have become a core component of patient-centered care. Limited research exists on such portal use in patients after kidney transplantation. The aim of this study was to examine preoperative, perioperative, and postoperative factors associated with post-transplantation portal use. METHODS: This cross-sectional study included all patients who underwent kidney transplantation from April 2016 to May 2019 at the University of Toledo Medical Center. Exclusion criteria included international travel for transplantation and those without available postoperative lab or follow-up records. Data were collected for 2 y post-transplantation. Univariable and multivariable linear regression was performed to determine associations with portal use. RESULTS: Two hundred and forty-seven kidney transplant recipients were included in the study; 35.6% (n = 88) used the portal versus 64.4% (n = 159) did not. Preoperative factors associated with increased use included income >$40,000 (odds ratio [OR], 2.95; P = 0.006) and cancer history (OR, 2.46; P = 0.007), whereas diabetes history had reduced use (OR, 0.51; P = 0.021). The Black race had the least use. Perioperatively, reduced use was associated with dialysis before transplant (OR, 0.25; P < 0.001) and hospital stay ≥4 d (OR, 0.49; P = 0.009). Postoperatively, associations with increased use included average eGFR >30 (P = 0.04) and hospital readmissions (n = 102), whereas those with ER (n = 138) visits had decreased use. Multivariable analysis revealed increased use with income >$40,000 (OR, 2.51; P = 0.033). CONCLUSIONS: There was no observed difference in clinical outcomes for portal users and nonusers undergoing kidney transplantation, although portal use may decrease the likelihood of ER visits. Socioeconomic status and ethnicity may play a role on who utilizes the patient portals.

Ethnic and Racial Diversity Among Surgeon and Non-Surgeon Deans of Allopathic Medical Schools.

INTRODUCTION: Previous publications have assessed the diversity among medical students, residents, faculty, and department leaders in surgery and medicine overall. We aim to evaluate the diversity among medical school deans in the United States. We quantify and compare the representation of women and underrepresented minority surgeon and non-surgeons. METHODS: 151 allopathic medical schools were included. Data regarding demographics, education, training, and previous leadership position were collected from institutional websites, online resources, and July 2021 Association of American Medical Colleges Council of Deans. Demographics for surgeon and non-surgeon were compared using chi square and logistic regression with 5% significance interval. RESULTS: 21.9% (n = 33) of all medical school deans were surgeons. 21.2% (n = 7) were women, which was not significantly different from non-surgeons (22%, P = .92). All the women surgeons were non-Hispanic white, similar to all deans (P = .83). 78.8% (n = 26) of all surgeon deans were non-Hispanic White compared to 84.7% (n = 100) overall (P = .28). There were 13 Black deans, four of whom were surgeons, and only one Hispanic dean, who was not a surgeon. Surgeons were more likely to be fellows of their professional society (P = .012). CONCLUSION: The demographic diversity of surgeon and non-surgeon US medical school deans is not significantly different. The deficiencies in leadership diversity in medicine persists among medical school deans. There remains substantial room to improve the representation of women and underrepresented minorities as deans.

Impact of darolutamide on local symptoms: pre-planned and post hoc analyses of the ARAMIS trial.

OBJECTIVE: To assess, the effect of darolutamide (a structurally distinct androgen receptor inhibitor) on urinary and bowel symptoms, using data from the phase III ARAMIS trial (NCT02200614) that showed darolutamide significantly reduced the risk of metastasis and death versus placebo. PATIENTS AND METHODS: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554). Local symptom control was assessed by first prostate cancer-related invasive procedures and post hoc analyses of time to deterioration in quality of life (QoL) using total urinary and bowel symptoms, and individual questions for these symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module subscales and Functional Assessment of Cancer Therapy-Prostate prostate cancer subscale. Prostate-specific antigen (PSA) responses were correlated with urinary and bowel adverse events (AEs). RESULTS: Fewer patients receiving darolutamide (4.7%) versus placebo (9.6%) underwent invasive procedures, and time to first procedure was prolonged with darolutamide (hazard ratio 0.42, 95% confidence interval 0.28-0.62). Darolutamide significantly (P < 0.01) delayed worsening of QoL for total urinary and bowel symptoms versus placebo, mostly attributed by individual symptoms of urinary frequency, associated pain, and interference with daily activities. AEs of urinary retention and dysuria were less frequent with darolutamide, and greater PSA response (≥90%, ≥50% and <90%, <50%) among darolutamide-treated patients was associated with lower incidences of urinary retention (2.2%, 4.2%, 5.1%) and dysuria (0.5%, 3.2%, 5.1%), respectively. CONCLUSIONS: Darolutamide demonstrated a positive impact on local disease recurrence and symptom control in patients with nmCRPC, delayed time to deterioration in QoL related to urinary and bowel symptoms, and a favourable safety profile showing similar incidence of urinary- and bowel-related AEs compared with placebo.