Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial.

BACKGROUND AND OBJECTIVE: Trough abiraterone concentration (ABI Cmin) of 8.4 ng/mL has been identified as an appropriate efficacy threshold in patients treated for metastatic castration-resistant prostate cancer (mCRPC). The aim of the phase II OPTIMABI study was to evaluate the efficacy of pharmacokinetics (PK)-guided dose escalation of abiraterone acetate (AA) in underexposed patients with mCRPC with early tumour progression. METHODS: This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone Cmin was measured 22-26 h after the last dose intake each month during the first 12 weeks of treatment. In step 2, underexposed patients (Cmin < 8.4 ng/mL) with tumour progression within the first 6 months of treatment were enrolled and received AA 1000 mg twice daily. The primary endpoint was the rate of non-progression at 12 weeks after the dose doubling. During step 1, adherence to ABI treatment was assessed using the Girerd self-reported questionnaire. A post-hoc analysis of pharmacokinetic (PK) data was conducted using Bayesian estimation of Cmin from samples collected outside the sampling guidelines (22-26 h). RESULTS: In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI Cmin in the two groups. Four patients were enrolled in step 2, and all reached the exposure target (Cmin > 8.4 ng/mL) after doubling the dose, but none met the primary endpoint. In the post-hoc analysis of PK data, 32 patients (39%) were underexposed, and ABI Cmin was independently associated with worse progression-free survival [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.07-5.81; p = 0.03], in contrast to the ITT analysis. CONCLUSION: The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15).

The Quality of Menu Offerings in Independently Owned Restaurants in Baltimore, Maryland: Results from Mixed-Methods Formative Research for the FRESH Trial.

(1) Background: Independently owned restaurants (IORs) are prevalent in under-resourced racial and ethnic minority communities in the US and present a unique setting for public health nutrition interventions. (2) Methods: We conducted 14 in-depth interviews with IOR owners in Baltimore about their perceptions of healthy food, and customers' acceptance of healthier menus and cooking methods and concurrent observations of the availability of healthy options on their menus. Qualitative data were coded and analyzed using ATLAS.ti. Observations were analyzed with statistical analysis performed in R. (3) Results: Owners perceived non-fried options, lean proteins, and plant-based meals as healthy. While open to using healthier cooking fats, they had mixed feelings about reducing salt, adopting non-frying methods for cooking, and adding vegetables and whole grains to the menu, and were reluctant to reduce sugar in recipes and beverages. Only 17.5% of 1019 foods and 27.6% of 174 beverages in these IORs were healthy, with no significant differences in the healthfulness of restaurant offerings within low-healthy-food-access/low-income neighborhoods and those outside. (4) Conclusion: Healthy options are generally scarce in Baltimore's IORs. Insights from owners inform future interventions to tailor healthy menu offerings that are well-received by customers and feasible for implementation.

Characterization of a cytokinin-binding protein locus in Mycobacterium tuberculosis.

Cytokinins are adenine-based hormones that have been well-characterized in plants but are also made by bacteria, including the human-exclusive pathogen Mycobacterium tuberculosis . In M. tuberculosis , cytokinins activate transcription of an operon that affects the bacterial cell envelope. In plants, cytokinins are broken down by dedicated enzymes called cytokinin oxidases into adenine and various aldehydes. In proteasome degradation-deficient M. tuberculosis , the cytokinin-producing enzyme Log accumulates, resulting in the buildup of at least one cytokinin-associated aldehyde. We therefore hypothesized that M. tuberculosis encodes one or more cytokinin oxidases. Using a homology-based search for homologs of a plant cytokinin oxidase, we identified Rv3719 and a putative cytokinin-specific binding protein, Rv3718c. Deletion of the locus encoding these proteins did not have a measurable effect on in vitro growth. Nonetheless, Rv3718c bound a cytokinin with high specificity. Our data thus support a model whereby cytokinins play one or more roles in mycobacterial physiology. IMPORTANCE: Numerous bacterial species encode cytokinin-producing enzymes, the functions of which are almost completely unknown. This work contributes new knowledge to the cytokinin field for bacteria, and also revealed further conservation of cytokinin-associated proteins between plants and prokaryotes.

Does PaCO2 correction have an impact on survival of patients with chronic respiratory failure and long-term non-invasive ventilation?

Background and objective: Non-invasive ventilation (NIV) improves survival of patients with chronic respiratory failure (CRF). Most often, pressure settings are made to normalize arterial blood gases. However, this objective is not always achieved due to intolerance to increased pressure or poor compliance. Few studies have assessed the effect of persistent hypercapnia on ventilated patients' survival. Data from the Pays de la Loire Respiratory Health Research Institute cohort were analyzed to answer this question. Study design and methods: NIV-treated adults enrolled between 2009 and 2019 were divided into 5 subgroups: obesity-hypoventilation syndrome (OHS), COPD, obese COPD, neuromuscular disease (NMD) and chest wall disease (CWD). PaCO2 correction was defined as the achievement of a PaCO2 < 6 kPa or a 20% decrease in baseline PaCO2 in COPD patients. The endpoint was all-cause mortality. Follow-up was censored in case of NIV discontinuation. Results: Data from 431 patients were analyzed. Median survival was 103 months and 148 patients died. Overall, PaCO2 correction was achieved in 74% of patients. Bivariate analysis did not show any survival difference between patients who achievedPaCO2 correction and those who remained hypercapnic: overall population: p = 0.74; COPD: p = 0.97; obese COPD: p = 0.28; OHS: p = 0.93; NMD: p = 0.84; CWD: p = 0.28. Conclusion: Moderate residual hypercapnia under NIV does not negatively impact survival in CRF patients. In individuals with poor tolerance of pressure increases, residual hypercapnia can therefore be tolerated under long-term NIV. Larger studies, especially with a higher number of patients with residual PaCO2 > 7 kPa, are needed to confirm these results.

Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage.

Clostridioides difficile damages the colonic mucosa through the action of two potent exotoxins. Factors shaping C. difficile pathogenesis are incompletely understood but are likely due to the ecological factors in the gastrointestinal ecosystem, mucosal immune responses, and environmental factors. Little is known about the role of pharmaceutical drugs during C. difficile infection (CDI), but recent studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) worsen CDI. The mechanism underlying this phenomenon remains unclear. Here, we show that NSAIDs exacerbate CDI by disrupting colonic epithelial cells (CECs) and sensitizing cells to C. difficile toxin-mediated damage independent of their canonical role of inhibiting cyclooxygenase (COX) enzymes. Notably, we find that NSAIDs and C. difficile toxins target the mitochondria of CECs and enhance C. difficile toxin-mediated damage. Our results demonstrate that NSAIDs exacerbate CDI by synergizing with C. difficile toxins to damage host cell mitochondria. Together, this work highlights a role for NSAIDs in exacerbating microbial infection in the colon.

Experiences of Inter-Hospital Transfers (IHT) by Patients and Relatives during the COVID-19 Pandemic in France: A Qualitative Study.

BACKGROUND: The first wave of the COVID-19 epidemic led to a rapid and unexpected saturation of the French ICU, forcing the health care system to adapt. Among other emergency measures, inter-hospital transfers were carried out. OBJECTIVE: To assess the psychological experience of patients and their relatives regarding inter-hospital transfers. METHODS: Semi-structured interviews were conducted with transferred patients and their relatives. A phenomenological study design was used to examine subjective experiences and their meanings for the participants. RESULTS: The analysis found nine axes pertaining to the experiences of IHT (inter-hospital transfers), grouped in three super-ordinate themes: Information about inter-hospital transfers, differences in patients' and relatives' experiences, and host hospital experience. It appears that patients felt little impacted by the transfers, unlike relatives who experienced intense anxiety when the transfer was announced. Good communications between patients and their relatives resulted in a good level of satisfaction regarding their host hospitals. COVID-19 and its somatic consequences seem to have had more psychological impact on the participants than the transfers by themselves. CONCLUSION: Our results suggest that there are limited current psychological consequences of the IHT implemented during the first wave of COVID-19, although the involvement of patients and their relatives in the organization of the IHT at the time of transfer could further limit them.

Developing an Evidence-Based Nutrition Curriculum for Correctional Settings.

People experiencing incarceration in the United States face numerous health disparities before, during, and after imprisonment, with prison conditions often exacerbating the severity of their health conditions. Within prisons, inadequate nutrition may contribute to the high prevalence of chronic disease such as diabetes and heart disease. This article discusses the development of an evidence-based nutrition curriculum for prison settings, informed by literature on current nutrition in prison, as well as previous health interventions designed to improve the health of incarcerated individuals. The curriculum was developed using guidelines for an effective health curriculum from the Centers for Disease Control and Prevention. Furthermore, this article discusses the theoretical foundations and effective pedagogies for teaching health materials in prison and provides further recommendations for improving nutrition in correctional institutions.

Social inequalities in treatment receipt for childhood cancers in Ireland: A population-based analysis.

Treatment advances over the past five decades have resulted in significant improvements in survival from childhood cancer. Although survival rates are relatively high, social disparities in outcomes have been sometimes observed. In a population-based study, we investigated social inequalities by sex and deprivation in treatment receipt in childhood cancer in Ireland. Cancers incident in people aged 0 to 19 during 1994 to 2012 and treatments received were abstracted from the National Cancer Registry Ireland. Multivariable modified Poisson regression with robust error variance (adjusting for age, and year) was used to assess associations between sex and deprivation category of area of residence at diagnosis and receipt of cancer-directed surgery, chemotherapy or radiotherapy. Three thousand seven hundred and four childhood cancers were included. Girls were significantly less likely than boys to receive radiotherapy for leukemia overall (relative risk [RR] = 0.70; 95% confidence interval [CI] = 0.50-0.98), and acute lymphoblastic leukemia specifically (RR = 0.54; 95% CI = 0.36-0.79), and surgery for central nervous system (CNS) overall (RR = 0.83; 95% CI = 0.74-0.93) and other CNS (RR = 0.76; 95% CI = 0.60-0.96). Girls were slightly less likely to receive chemotherapy for non-Hodgkin lymphoma and surgery for Hodgkin lymphoma (HL), but these results were not statistically significant. Children residing in more deprived areas were significantly less likely to receive chemotherapy for acute myeloid leukemia or surgery for lymphoma overall and HL, but more likely to receive chemotherapy for medulloblastoma. These results may suggest social inequalities in treatment receipt for childhood cancers. Further research is warranted to explore whether similar patterns are evident in other childhood cancer populations and to better understand the reasons for the findings.

Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics.

Clostridioides difficile is a Gram-positive anaerobe that can cause a spectrum of disorders that range in severity from mild diarrhoea to fulminant colitis and/or death. The bacterium produces up to three toxins, which are considered the major virulence factors in C. difficile infection. These toxins promote inflammation, tissue damage and diarrhoea. In this Review, we highlight recent biochemical and structural advances in our understanding of the mechanisms that govern host-toxin interactions. Understanding how C. difficile toxins affect the host forms a foundation for developing novel strategies for treatment and prevention of C. difficile infection.

Priapism in the newborn: Management of a case.

Priapism is extremely rare in newborns and generally idiopathic. The objective of present paper is to report the case of a newborn with priapism on the 2nd day of life. Clinical and paraclinical assessment did not reveal an etiology. Conservative management was instituted and the erection resolved fully on the fourth day of life.

Soft drinks and premiums with children's meals marketed on the websites of the top restaurant chains worldwide.

OBJECTIVE: To assess the frequency with which soft drinks and premiums are available with children's meals marketed on the top restaurant chains' websites worldwide. DESIGN: Cross-sectional structured observational assessment of secondary information about top international restaurant chain children's meals. SETTING: Websites of top restaurant chains for 193 countries and five regions of the United Nations. PARTICIPANTS: Top restaurant chains (including McDonald's, Subway, Burger King and KFC) across 193 countries. Children's meal images and descriptions were reviewed to determine if the meal was marketed with a soft drink as a beverage option and whether the meal offered a premium. RESULTS: Children's meals were marketed online on restaurant websites by at least one of the four chains in a total of seventy eight of the 193 countries (40·4 %). Overall, 56·3 % of countries with any online children's meal marketing by the four chains included at least one chain that marketed soft drinks and 92·3 % marketed premiums with the meal. CONCLUSIONS: Every region in the world includes marketing of children's meals on the websites of the top restaurant chains. The high prevalence of premiums marketed online with children's meals is of concern. Similarly, with over 50 % of countries with online children's meal marketing having at least one chain that offers soft drinks as part of the meals, additional regulation and education may be warranted.

Compared outcomes of femoral shaft fracture treatment in school-age children in Sub-Saharan Africa: Primary open reduction and intramedullary K-wire fixation versus traction followed by spica cast.

BACKGROUND: Elastic stable intramedullary nailing has become the treatment of choice for femur shaft fractures in school-age children in developed world. However, in the sub-Saharan Africa, this management is still challenging because of the lack of fluoroscopy in more hospitals. We performed either primary open reduction and intramedullary K-wire fixation (PORIKF) or conservative treatment. The aim of this study was to compare the clinical and functional outcomes of these two procedures employed. PATIENTS AND METHODS: This retrospective study included 62 children with 64 fractures (10 years on an average; range: 6-15 years) treating for femoral shaft fractures either by PORIKF (n = 21; 23 fractures) or skin traction followed by spica cast (n = 41) between 2008 and 2017. Outcomes were assessed using Flynn criteria. Comparisons were made by Fisher and Student's t-test with a significant P < 5%. RESULTS: Outcomes were satisfactory in 21 cases (91%) in the PORIKF group compared with 32 (78%) in the conservative group (P = 0.3012). The average hospital stay was 18.6 days in the PORIKF group, whereas it was 20 in the conservative group (P = 0.0601). The mean time for bone union was 13.9 weeks in the PORIKF group and 13.2 weeks in the conservative group, (P = 0.4346). There was a statistically significant difference between the two groups in terms of major complications (P = 0.0177). One patient had osteomyelitis in the PORIKF group. Unacceptable shortening >2 cm was observed only in the conservative group. The average time to return to daily activities was 30 days shorter in the PORIKF group when compared to conservative group (P < 0.05). CONCLUSION: PORIKF provides better results than conservative treatment. Open reduction did not increase the rate of infectious complication.

Murine Intrarectal Instillation of Purified Recombinant Clostridioides difficile Toxins Enables Mechanistic Studies of Pathogenesis.

Clostridioides difficile is linked to nearly 225,000 antibiotic-associated diarrheal infections and almost 13,000 deaths per year in the United States. Pathogenic strains of C. difficile produce toxin A (TcdA) and toxin B (TcdB), which can directly kill cells and induce an inflammatory response in the colonic mucosa. Hirota et al. (S. A. Hirota et al., Infect Immun 80:4474-4484, 2012) first introduced the intrarectal instillation model of intoxication using TcdA and TcdB purified from VPI 10463 (VPI 10463 reference strain [ATCC 43255]) and 630 C. difficile strains. Here, we expand this technique by instilling purified, recombinant TcdA and TcdB, which allows for the interrogation of how specifically mutated toxins affect tissue. Mouse colons were processed and stained with hematoxylin and eosin for blinded evaluation and scoring by a board-certified gastrointestinal pathologist. The amount of TcdA or TcdB needed to produce damage was lower than previously reported in vivo and ex vivo Furthermore, TcdB mutants lacking either endosomal pore formation or glucosyltransferase activity resemble sham negative controls. Immunofluorescent staining revealed how TcdB initially damages colonic tissue by altering the epithelial architecture closest to the lumen. Tissue sections were also immunostained for markers of acute inflammatory infiltration. These staining patterns were compared to slides from a human C. difficile infection (CDI). The intrarectal instillation mouse model with purified recombinant TcdA and/or TcdB provides the flexibility needed to better understand structure/function relationships across different stages of CDI pathogenesis.

Structural elucidation of the Clostridioides difficile transferase toxin reveals a single-site binding mode for the enzyme.

Clostridioides difficile is a Gram-positive, pathogenic bacterium and a prominent cause of hospital-acquired diarrhea in the United States. The symptoms of C. difficile infection are caused by the activity of three large toxins known as toxin A (TcdA), toxin B (TcdB), and the C. difficile transferase toxin (CDT). Reported here is a 3.8-Å cryo-electron microscopy (cryo-EM) structure of CDT, a bipartite toxin comprised of the proteins CDTa and CDTb. We observe a single molecule of CDTa bound to a CDTb heptamer. The formation of the CDT complex relies on the interaction of an N-terminal adaptor and pseudoenzyme domain of CDTa with six subunits of the CDTb heptamer. CDTb is observed in a preinsertion state, a conformation observed in the transition of prepore to ß-barrel pore, although we also observe a single bound CDTa in the prepore and ß-barrel conformations of CDTb. The binding interaction appears to prime CDTa for translocation as the adaptor subdomain enters the lumen of the preinsertion state channel. These structural observations advance the understanding of how a single protein, CDTb, can mediate the delivery of a large enzyme, CDTa, into the cytosol of mammalian cells.

Educational attainment of childhood cancer survivors: A systematic review.

BACKGROUND: Advances in treatment mean that most children diagnosed with cancer during childhood survive. Therefore, it is increasingly important to examine the long-term consequences of childhood cancer, including educational attainment. This systematic review investigated whether the educational attainment of childhood cancer survivors differ from the cancer-free population. DESIGN/METHODS: We searched seven databases for articles published from January 2005 to August 2018. We identified full papers in English, reporting primary data on academic attainment of adult survivors of childhood cancer, compared to a control group. Quality appraisal was conducted using the Newcastle-Ottawa Scale. RESULTS: Fourteen studies met the inclusion criteria. Nine papers included patients with various types of cancers, four focused on a single type of cancer, and one on patients who underwent stem cell transplantation. Of the 14 papers, 2 studies were considered good quality, 10 were considered adequate quality, and 2 were considered poor quality. Four studies reported more favorable educational attainment among survivors while six did not report significant differences. Less favorable attainment was consistently reported for CNS survivors in four studies. CONCLUSION: The literature does not provide a clear pattern of the long-term consequences of childhood cancer on education attainment. While this may suggest that there is no consistent difference between the education attainment of cancer survivors and controls, it may also be the result of limitations in the existing research. To better assess the education attainment of survivors, there is a need for high-quality studies, with appropriate comparators, and standardized measures of education attainment across countries.

The NC domain of HIV-1 Gag contributes to the interaction of Gag with TSG101.

BACKGROUND: HIV-1 Gag polyprotein orchestrates the assembly of viral particles. Its C-terminus consists of the nucleocapsid (NC) domain that interacts with RNA, and the p6 domain containing the PTAP motif that binds the cellular ESCRT factor TSG101 and ALIX. Deletion of the NC domain of Gag (GagNC) results in defective Gag assembly, a decrease in virus production and, thus probably affects recruitment of the ESCRT machinery. To investigate the role of GagNC in this recruitment, we analysed its impact on TSG101 and ALIX localisations and interactions in cells expressing Gag. METHODS: Cells expressing mCherry-Gag or derivatives, alone or together with eGFP-TSG101 or eGFP-ALIX, were analysed by confocal microscopy and FLIM-FRET. Chemical shift mapping between TSG101-UEV motif and Gag C-terminus was performed by NMR. RESULTS: We show that deletion of NC or of its two zinc fingers decreases the amount of Gag-TSG101 interacting complexes in cells. These findings are supported by NMR data showing chemical shift perturbations in the NC domain in- and outside - of the zinc finger elements upon TSG101 binding. The NMR data further identify a large stretch of amino acids within the p6 domain directly interacting with TSG101. CONCLUSION: The NC zinc fingers and p6 domain of Gag participate in the formation of the Gag-TSG101 complex and in its cellular localisation. GENERAL SIGNIFICANCE: This study illustrates that the NC and p6 domains cooperate in the interaction with TSG101 during HIV-1 budding. In addition, details on the Gag-TSG101 complex were obtained by combining two high resolution biophysical techniques.

Urban-Rural Variations in Quality-of-Life in Breast Cancer Survivors Prescribed Endocrine Therapy.

The number of breast cancer survivors has increased as a result of rising incidence and increased survival. Research has revealed significant urban-rural variation in clinical aspects of breast cancer but evidence in the area of survivorship is limited. We aimed to investigate whether quality of life (QoL) and treatment-related symptoms vary between urban and rural breast cancer survivors prescribed endocrine therapy. Women with a diagnosis of stages I-III breast cancer prescribed endocrine therapy were identified from the National Cancer Registry Ireland and invited to complete a postal survey (N = 1606; response rate = 66%). A composite measure of urban-rural classification was created using settlement size, population density and proximity to treatment hospital. QoL was measured using the Functional Assessment of Cancer Therapy (FACT-G) and an endocrine subscale. The association between urban-rural residence/status and QoL and endocrine symptoms was assessed using linear regression with adjustment for socio-demographic and clinical covariates. In multivariable analysis, rural survivors had a statistically significant higher overall QoL (ß = 3.81, standard error (SE) 1.30, p < 0.01), emotional QoL (ß = 0.70, SE 0.21, p < 0.01) and experienced a lower symptom burden (ß = 1.76, SE 0.65, p < 0.01) than urban survivors. QoL in breast cancer survivors is not simply about proximity and access to healthcare services but may include individual and community level psychosocial factors.

Urban-rural differences in cancer-directed surgery and survival of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Clinically appropriate cancer-directed surgery is an influential and significant prognostic factor. In a population-based study, we determined how urban/rural residence was related to surgery receipt for patients with non-small cell lung cancer. We assessed the relationship between relative survival and patients' area of residence, taking into account surgery receipt and area socioeconomic level. METHODS: We extracted data from the National Cancer Registry Ireland on patients with non-small cell lung cancer diagnosed during 1994-2011 and linked to area-level data on socioeconomic indicators and urban/rural categories. We calculated ORs for receipt of cancer-directed surgery using logistic regression with postestimation of adjusted proportions. Relative survival estimates with follow-up to 31 December 2012 were calculated for all cases and stratified by surgery receipt, adjusting for clinical variables, area socioeconomic level and other sociodemographic characteristics. RESULTS: 15 031 people diagnosed with non-small cell lung cancer were included in the analysis. On the basis of the multiple logistic regression model, a significantly larger proportion of urban patients (adjusted proportion 23%) as compared with rural patients (adjusted proportion 21%) received surgery (p<0.001). In multivariate analysis, rural residence was significantly related to a decrease in excess mortality for all cases (HR 0.90, 95% CI 0.87 to 0.94, p<0.001) and for non-surgical cases (HR 0.88, 95% CI 0.85 to 0.92, p<0.001). CONCLUSIONS: The findings point to the need for targeted policies addressing access to treatment for rural patients with non-small cell lung cancer.

Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks.

AIM: We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. METHODS: We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. RESULTS: The men (n = 7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area-level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01-1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14-2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02-1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09-1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. CONCLUSIONS: Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority.