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Despite theoretical benefits of intermittent as compared with continuous androgen-deprivation therapy in patients with metastatic prostate cancer, intermittent therapy did not result in longer survival or long-term improvement in quality of life. Prostate cancer is an androgen-dependent disease, and continuous androgen deprivation has been the standard therapy for metastatic hormone-sensitive disease. Despite a high response rate, resistance to androgen-deprivation therapy occurs in most patients, resulting in a median survival of 2.5 to 3 years. 1 , 2 There is evidence suggesting that progression to castration resistance is adaptive in part, and pathways involving the androgen receptor, as well as cell-survival pathways independent of the androgen receptor, have been implicated. 3 , 4 Data from an androgen-dependent tumor model have suggested that androgen withdrawal alters the ratio of putative stem cells in the tumor-cell population. 5 Initially, differentiated . . .

To examine predictors of adherence in a randomized controlled trial of resistance exercise training (RET) in prostate cancer survivors receiving androgen deprivation therapy. A randomized controlled trial conducted at fitness centers in Ottawa and Edmonton, Canada. Prostate cancer survivors ( n = 155) completed measures of social cognitive variables, quality of life (QOL), behavior, and fitness before being randomized to either an exercise ( n = 82) or control ( n = 73) group. The exercise group was asked to perform supervised RET three times per week for 12 weeks. The exercise group attended 28.2 of the 36 (78.3%) RET sessions. Univariate analyses revealed eight different significant ( Ps < .05) predictors of exercise adherence including exercise stage of change, intention, age, QOL, fatigue, subjective norm, leg-press test, and perceived behavioral control. A multivariate analysis indicated that there were three independent predictors of adherence that explained 20.4% of the variance: exercise stage of change (β = 0.26; P = .013), age (β = −0.22; P = .037), and intention (β = 0.19; P = .073). Exercise adherence in the trial was very good but not optimal. Adherence was predicted by variables from many different categories including social cognitive, QOL, behavioral, fitness, and demographic. These findings may have important implications for maximizing adherence during clinical trials of exercise in prostate cancer survivors.

In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received chemotherapy. Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide. 1 Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941. 2 Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer. 3 , 4 However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease. 5 – 9 In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone [LHRH] analogue or orchiectomy with . . .

Goals of work Although exercise has gained recognition as an effective supportive care intervention for cancer survivors, exercise participation rates are low. The present study examined the determinants of exercise in bladder cancer survivors using the Theory of Planned Behavior (TPB). Patients and methods Bladder cancer survivors ( N  = 397) residing in Alberta, Canada completed a mailed questionnaire at baseline that assessed demographic, medical, behavioral, and social cognitive variables and a second questionnaire 3 months later that assessed exercise. Multiple regression was the primary analysis. Main results Adjuvant therapy ( r  = −0.10, p  = 0.021), cancer invasiveness ( r  = −0.10, p  = 0.051), and age ( r  = −0.11, p  = 0.037) were all negatively associated with exercise. Intention ( β  = 0.25, p  < 0.001), perceived behavioral control ( β  = 0.18, p  = 0.001), and planning ( β  = 0.12, p  = 0.018) explained 20.9% of the variance in exercise over a 3-month period. Perceived behavioral control ( β  = 0.32, p  < 0.001), affective attitude ( β  = 0.18, p  = 0.002), instrumental attitude ( β  = 0.15, p  = 0.025) and descriptive norm ( β  = 0.10, p  = 0.032) explained 39.1% of the variability in exercise intention. Constructs from the TPB mediated the associations between adjuvant therapy, cancer invasiveness, age, and exercise. Age and adjuvant therapy also moderated some of the associations within the TPB. Conclusions Some medical and demographic variables predict exercise behavior in bladder cancer survivors, but these associations are mediated by the TPB. Interventions based on the TPB may be effective for promoting exercise in this cancer survivor population.

The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy. The diagnosis of MGRS-related disease is established by kidney biopsy and immunofluorescence studies to identify the monotypic immunoglobulin deposits (although these deposits are minimal in patients with either C3 glomerulopathy or thrombotic microangiopathy). Accordingly, the IKMG recommends a kidney biopsy in patients suspected of having MGRS to maximize the chance of correct diagnosis. Serum and urine protein electrophoresis and immunofixation, as well as analyses of serum free light chains, should also be performed to identify the monoclonal immunoglobulin, which helps to establish the diagnosis of MGRS and might also be useful for assessing responses to treatment. Finally, bone marrow aspiration and biopsy should be conducted to identify the lymphoproliferative clone. Flow cytometry can be helpful in identifying small clones. Additional genetic tests and fluorescent in situ hybridization studies are helpful for clonal identification and for generating treatment recommendations. Treatment of MGRS was not addressed at the 2017 IKMG meeting; consequently, this Expert Consensus Document does not include any recommendations for the treatment of patients with MGRS.

Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice. An updated set of reporting standards for the development, interpretation and evaluation of polygenic risk scores is presented, which should aid the translation of these scores into clinical applications.

Background: Prevalence, incidence, and factors associated with posttraumatic stress disorder (PTSD) symptoms at follow-up among healthcare workers after the first wave of the COVID-19 pandemic are unknown. Methods: A web survey invitation was sent to healthcare worker listservs at a NYC medical center (April, 2020). The Primary Care (PC)-PTSD questionnaire was used to screen for PTSD symptoms at baseline and then every 2 weeks for 10 weeks. Incidence and prevalence of PTSD symptoms were determined at each time point. Multivariable generalized estimating equation models were performed to investigate the factors associated with a positive PC-PTSD screen at follow-up. Results: Median age (interquartile range) of N = 230 participants was 36 (31–48) years; 79.6% were women; 82.6% worked in COVID-19-focused settings. The prevalence of PTSD symptoms decreased from 55.2% at baseline to 25.0% at 10 weeks (p < 0.001). Among participants who had a baseline negative screen for PTSD symptoms, the incidence of PTSD at 10 weeks was 12.2% (p-trend 0.034). In multivariable-adjusted analyses, being a nurse (odds ratio [OR]: 1.70, 95% confidence interval [CI]: 1.06–2.71), female (OR: 3.00, 95% CI: 1.59, 5.72), and working in a COVID-19-focused location (OR: 1.51, 95% CI: 1.02, 2.21) were associated with increased odds of PTSD symptoms at 10-weeks. Conclusions: PTSD symptoms improved over 3 months following the first wave of the COVID-19 pandemic. However, one out of four NYC healthcare workers still had an increased risk for PTSD at 10-weeks. Screening healthcare workers for PTSD symptoms should be considered during the COVID-19 pandemic.

In the key to Figure 1 of this article, ‘Amyloid microtubules’ has been corrected to ‘Microtubules’.

Background Thymidine analogs, namely AZT (Zidovudine or Retrovir™) and d4T (Stavudine or Zerit™) are antiretroviral drugs still employed in over 75% of first line combination antiretroviral therapy (cART) in Kampala, Uganda despite aversion to prescribing these drugs for cART in high income countries due in part to adverse events. For this study, we explored how the continued use of these thymidine analogs in cART could impact emergence of drug resistance and impact on future treatment success in Uganda, a low-income country. Methods We examined the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients failing a first line combined antiretroviral treatment containing either AZT or d4T, which represents approximately 5% of the patients at the Joint Clinical Research Center receiving a AZT or d4T containing treatment. Next generation sequencing (DEEPGEN™HIV) and multiplex oligonucleotide ligation assays (AfriPOLA) were then performed on a subset of patient samples to detect low frequency drug resistant mutations. CD4 cell counts, viral RNA loads, and treatment changes were analyzed in a cohort of treatment success and failures. Results Over 80% of patients failing first line AZT/d4T-containing cART had predicted drug resistance to 3TC (Lamivudine) and non-nucleoside RT inhibitors (NNRTIs) in the treatment regimen but only 45% had resistance AZT/d4T associated resistance mutations (TAMs). TAMs were however detected at low frequency within the patients HIV quasispecies (1–20%) in 21 of 34 individuals who were failing first-line AZT-containing cART and lacked TAMs by Sanger. Due to lack of TAMs by Sanger, AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic success. Conclusions Our findings suggest that continued use of AZT and d4T in first-line treatment in low-to-middle income countries may lead to misdiagnosis of HIV-1 drug resistance and possibly enhance a succession of second- and third-line treatment failures.

Renal-cell carcinoma is the 10th most common cancer in Western countries, with about 30,600 new cases diagnosed and 12,000 deaths from the disease in the United States during 1996. 1 Surgical resection of localized disease is the only curative treatment. Approximately one third of patients present with metastatic disease, which is incurable except in a few patients who undergo surgical excision of a solitary soft-tissue metastasis. The median duration of survival of patients with metastatic renal-cell carcinoma is about one year, and only 10 percent survive beyond two years. 2 The results remain poor because of resistance to conventional therapies, such as . . .