Perpetuating and protective factors in insomnia across racial/ethnic groups of veterans.

Few studies have examined racial/ethnic differences in rates and correlates of insomnia among veterans. This study compared rates of insomnia and interest in sleep treatment among veterans of diverse racial/ethnic backgrounds. Consistent with the 3P model, we tested racial discrimination as a predictor of insomnia, with post-traumatic stress disorder symptoms and romantic partners as perpetuating and protective moderators of this association, respectively. A total of 325 veterans (N = 236 veterans of colour; 12% Asian, 36% Black, 14% Hispanic/Latine) completed questionnaires online from remote locations. Descriptive statistics were used to compare patterns across racial/ethnic groups. Linear regression was used to test moderators of the association between racial discrimination and insomnia severity. Overall, 68% of participants screened positive for insomnia: 90% of Asian; 79% of Hispanic/Latine; 65% of Black; and 58% of White participants. Of those, 74% reported interest in sleep treatment, and 76% of those with partners reported interest in including their partner in treatment. Racial discrimination and post-traumatic stress disorder were correlated with more severe insomnia, while romantic partners were correlated with less severe insomnia. Only post-traumatic stress disorder moderated the association between racial discrimination and insomnia severity. Rates of insomnia were highest among Asian and Hispanic/Latine participants, yet these groups were among the least likely to express interest in sleep treatment. Racial discrimination may exacerbate insomnia symptoms among veterans, but only among those who do not already have disturbed sleep in the context of post-traumatic stress disorder. Romantic partners may serve as a protective factor in insomnia, but do not seem to mitigate the impact of racial discrimination.

Relationship Maintenance among Military Couples.

A burgeoning body of research on the relationship maintenance of military couples over the past two decades suggests the time is right to organize, assimilate, and critique the literature. We conducted a systematic review informed by the integrative model of relationship maintenance (Ogolsky et al., 2017) that considered issues of intersectionality (Crenshaw, 1991). Our literature search identified 81 relevant journal articles representing 62 unique samples. With respect to theory, 59.3% of the journal articles employed one or more formal theoretical frameworks. In terms of research design, 88.7% of the studies focused on the U.S. military, 83.9% of the studies recruited convenience samples, 54.8% of the studies utilized quantitative methods, and 30.6% of the studies collected longitudinal data. Among the studies reporting sample demographics, 96.8% of participants were married, 77.2% of participants identified as non-Hispanic White, and only one same-sex relationship was represented. Our narrative synthesis integrated findings about relationship maintenance from studies examining (a) relationship maintenance overtly, (b) communicating to stay connected across the deployment cycle, (c) disclosure and protective buffering, (d) support from a partner, (e) dyadic coping, and (f) caregiving and accommodating a partner's symptoms. We interpret our results with an eye toward advancing theory, research, and practice.

The effects of discrimination and psychological distress on U.S. Latino/a young adults' relational uncertainty and relationship instability.

OBJECTIVES: Racial/ethnic discrimination is a common and salient stressor for many individuals. Although discrimination can impair personal and relational well-being, little is known about its influences on the process of considering dissolution (i.e., relationship instability). In two studies of Latino/a young adults, we examined associations among discrimination, psychological distress, relational uncertainty, and relationship instability. METHOD: Study 1 assessed self-reports of 475 participants aged 18-29 (60.2% female, Mage = 24.8, SD = 3.22). Study 2 examined self-reports of 462 participants aged 18-29 (40.9% female, Mage = 25.9, SD = 2.72). Structural equation models evaluated direct and indirect associations among study variables. RESULTS: Discrimination was associated with relationship instability, both directly and indirectly via its associations with psychological distress and, in Study 1, relational uncertainty. CONCLUSIONS: Overall results suggest that racial/ethnic discrimination is associated with romantic relationship instability through its associations with psychological distress and uncertainty about the future of a relationship. Prior research demonstrates the resilience of Latino/a communities, and our findings reinforce the need for policies and clinical resources that reduce discrimination and support mental health and relationships. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perceived Experiences of Discrimination and Latino/a Young Adults' Personal and Relational Well-being.

US Latino/as experience high rates of discrimination, resulting in personal and relational distress. A sample of 238 Latino/a young adults (Mage = 25.37 years; 57.6% men; 54.4% Mexican) was used to investigate how perceived discrimination was associated with romantic relationship instability via young adults' depressive symptoms. The moderating roles of ethnic identity and romantic relationship maintenance on these associations were examined. Greater relationship maintenance and ethnic identity affirmation were associated with less depression and relationship instability. Under conditions of high ethnic identity exploration and resolution, the association between discrimination and depressive symptoms was stronger, leading to greater relationship instability. The findings reveal that the protective roles of cultural and relational factors may depend on the stressor and outcomes examined.

Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy-Naive Metastatic Castrate-Resistant Prostate Cancer.

LESSONS LEARNED: The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate-resistant prostate cancer (mCRPC).The negative data underscore that, despite a sound biological rationale and supportive early-phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge. BACKGROUND: Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor-induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy-naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6-month progression-free survival (PFS) rate between the two arms. Secondary endpoints included 6-month overall survival (OS), objective tumor and prostate-specific antigen (PSA) response rates, biomarkers, and adverse events. RESULTS: The 6-month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6-month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL-6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm). CONCLUSION: Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.

Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

Background: Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. Purpose: The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. Methods: A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Results: Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Conclusion: Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. Clinical Trial information: NCT02050906.

The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2. Phosphorylation of STAT1 and STAT5 was measured by flow cytometry and confirmed by immunoblot analysis. Changes in IFN-α- and IL-2-stimulated gene expression were measured by quantitative PCR, and changes in cytokine production were evaluated by ELISA. Cryopreserved PBMCs were obtained from cancer patients before and after receiving 400 mg sorafenib twice daily. Patient PBMCs were thawed, stimulated with IL-2 or IFN-α, and evaluated for phosphorylation of STAT1 and STAT5. Pretreatment of PBMCs with 10 µM sorafenib decreased STAT1 and STAT5 phosphorylation after treatment with IFN-α or IL-2. This inhibitory effect was observed in PBMCs from healthy donors over a range of concentrations of sorafenib (5-20 µM), IL-2 (2-24 nM), and IFN-α (10(1)-10(6) U/ml). This effect was observed in immune cell subsets, including T cells, B cells, NK cells, regulatory T cells, and myeloid-derived suppressor cells. Pretreatment with sorafenib also inhibited PBMC expression of IFN-α- and IL-2-regulated genes and inhibited NK cell production of IFN-γ, RANTES, MIP1-α, and MIG in response to IFN-α stimulation. PBMCs from patients receiving sorafenib therapy showed decreased responsiveness to IL-2 and IFN-α treatment. Sorafenib is a Raf kinase inhibitor that could have off-target effects on cytokine-induced signal transduction in immune effector cells.

Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: a phase III metastatic castration resistant prostate cancer trial.

Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p = 0.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p = 0.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step towards molecular CTC-based precision cancer management.

Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial.

BACKGROUND: The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases. METHODS: In a double-blind phase 3 trial, men with metastatic castration-resistant prostate cancer, stratified for progression type (prostate-specific antigen or radiological), baseline pain, extraskeletal metastases, and bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75 mg/m(2) every 21 days, intravenously) with atrasentan (10 mg/day, orally) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity. Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression-free survival (PFS) and overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00134056. FINDINGS: 498 patients were randomly assigned to the atrasentan group and 496 to the placebo group. The trial was halted early for futility in April, 2011, after a planned interim analysis. Median PFS was 9·2 months (95% CI 8·5-9·9) in the atrasentan group and 9·1 months (8·4-10·2) in the placebo group (hazard ratio 1·02, 0·89-1·16; p=0·81). Median overall survival was 17·8 months (16·4-19·8) in the atrasentan group versus 17·6 months (16·4-20·1) in the placebo group (1·04, 0·90-1·19; p=0·64). 278 (57%) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 (60%) of 486 in the placebo group (p=0·22). Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment. INTERPRETATION: Atrasentan, when added to docetaxel, does not improve overall survival or PFS in men with castration-resistant prostate cancer and bone metastases; therefore, single-agent docetaxel should remain as one of the standard treatments. FUNDED: National Cancer Institute, Sanofi-Aventis, and Abbott Laboratories.

The role of emotional dysregulation in the association between family-of-origin conflict and romantic relationship maintenance.

Family-of-origin systems are consequential for the emotional well-being of offspring. These influences are likely to last into adulthood, affecting adult children's romantic relationships. The mechanisms by which family-of-origin environments influence adult romantic relationships are not fully understood. In a sample of 118 different-sex couples, we tested the effects of negative family-of-origin conflict on adult offspring's provision of relationship maintenance to their romantic partner using structural equation modeling. We evaluated emotional dysregulation as a mediator of this effect, using two measures of emotional dysregulation. Results from structural models demonstrated a negative effect of family-of-origin conflict on the provision of relationship maintenance via higher levels of emotional dysregulation. Our results highlight emotional self-regulation as a valuable intervention point for couple therapists.

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC.

A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors.

PURPOSE: Prolonged exposure of cancer cells to triapine, an inhibitor of ribonucleotide reductase, followed by gemcitabine enhances gemcitabine activity in vitro. Fixed-dose-rate gemcitabine (FDR-G) has improved efficacy compared to standard-dose. We conducted a phase I trial to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of prolonged triapine infusion followed by FDR-G. EXPERIMENTAL DESIGN: Triapine was given as a 24-hour infusion, immediately followed by FDR-G (1000 mg/m(2) over 100-minute). Initially, this combination was administered days 1 and 8 of a 21-day cycle (Arm A, triapine starting dose 120 mg); but because of myelosuppression, it was changed to days 1 and 15 of a 28-day cycle (Arm B, starting dose of triapine 75 mg). Triapine steady-state concentrations (Css) and circulating ribonucleotide reductase M2-subunit (RRM2) were measured. RESULTS: Thirty-six patients were enrolled. The MTD was determined to be triapine 90 mg (24-hour infusion) immediately followed by gemcitabine 1000 mg/m(2) (100-minute infusion), every 2 weeks of a 4-week cycle. DLTs included grade 4 thrombocytopenia, leukopenia and neutropenia. The treatment was well tolerated with fatigue, nausea/vomiting, fever, transaminitis, and cytopenias being the most common toxicities. Among 30 evaluable patients, 1 had a partial response and 15 had stable disease. Triapine PK was similar, although more variable, compared to previous studies using doses normalized to body-surface-area. Steady decline in circulating levels of RRM2 may correlate with outcome. CONCLUSIONS: This combination was well tolerated and showed evidence of preliminary activity in this heavily pretreated patient population, including prior gemcitabine failure.

Are nanoporous materials radiation resistant?

The key to perfect radiation endurance is perfect recovery. Since surfaces are perfect sinks for defects, a porous material with a high surface to volume ratio has the potential to be extremely radiation tolerant, provided it is morphologically stable in a radiation environment. Experiments and computer simulations on nanoscale gold foams reported here show the existence of a window in the parameter space where foams are radiation tolerant. We analyze these results in terms of a model for the irradiation response that quantitatively locates such window that appears to be the consequence of the combined effect of two length scales dependent on the irradiation conditions: (i) foams with ligament diameters below a minimum value display ligament melting and breaking, together with compaction increasing with dose (this value is typically ∼5 nm for primary knock on atoms (PKA) of ∼15 keV in Au), while (ii) foams with ligament diameters above a maximum value show bulk behavior, that is, damage accumulation (few hundred nanometers for the PKA's energy and dose rate used in this study). In between these dimensions, (i.e., ∼100 nm in Au), defect migration to the ligament surface happens faster than the time between cascades, ensuring radiation resistance for a given dose-rate. We conclude that foams can be tailored to become radiation tolerant.

Translating Discovery Science. Fostering relationships: Service provider perspectives on community building among veteran families.

Objective: We sought to identify the social process through which communal support can be established among veteran couples and families. Background: On the basis of the social organization theory of action and change, a sense of community is crucial for military veterans' well-being and may serve as a resource for intervention. Method: We interviewed service providers (n = 8) and corroborated their perspectives by triangulating evaluations from veteran family participants (n = 143). Data were analyzed using grounded theory techniques. Results: Providers suggested promoting a sense of community in prevention and intervention programming by (a) establishing a safe and empowering space, (b) bridging existing gaps within family and community systems, and (c) encouraging interpersonal healing by promoting connection and facilitating the sharing of common experiences. Providers also described challenges to facilitating the program, including logistics, time, and funding constraints. Conclusion: According to our results, fostering community among veterans and their family members may be achieved by applying an integrative approach that goes beyond siloed individual, couple, and group therapy orchestrated by practitioners. Implications: We recommend multicomponent interventions that create synergy between different levels and forms of social support. Providers recommended being intentional about the program structure to focus on community strengths and shared connection.

Chemotherapy for the initial treatment of metastatic prostate adenocarcinoma and neuroendocrine carcinoma at diagnosis: real world application and impact in the SEER database (2004 -2018).

Background: Randomized controlled phase III trials have reported significant improvements in disease response and survival with the addition of chemotherapy to androgen deprivation therapy for men presenting with metastatic prostate cancer. We examined the implementation of such knowledge and its impact within the Surveillance, Epidemiology, and End Results (SEER) database. Method: The administration of chemotherapy for men with an initial presentation of metastatic prostate cancer from 2004 to 2018 in the SEER database and its association with survival outcomes was examined. Kaplan-Meier estimates were applied to compare survival curves. Cox proportion hazard survival models were used to analyze the association of chemotherapy and other variables with both cancer- specific and overall survival. Result: A total of 727,804 patients were identified with 99.9% presenting with adenocarcinoma and 0.1% with neuroendocrine histopathology. Chemotherapy as initial treatment for men with de novo distant metastatic adenocarcinoma increased from 5.8% during 2004-2013 to 21.4% during 2014-2018. Chemotherapy was associated with a poorer prognosis during 2004-2013 but was associated with improved cancer-specific (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.78-0.93, p=0.0004) and overall survival (HR= 0.78, 95% CI: 0.71-0.85, p < 0.0001) during 2014-2018. The improved prognosis during 2014-2018 was observed in patients with visceral or bone metastasis and most impactful for patients aged 71-80 years. These findings were confirmed by subsequent propensity score matching analyses. Furthermore, chemotherapy was consistently provided to 54% of patients with neuroendocrine carcinoma at diagnosis from 2004 to 2018. Treatment was associated with improved cancer-specific survival (HR= 0.62, 95% CI: 0.45-0.87, p=0.0055) and overall survival (HR= 0.69, 95% CI: 0.51-0. 94, p=0.0176) during 2014-2018 but not significant in earlier years. Conclusion: Chemotherapy at initial diagnosis was increasingly employed in men with metastatic adenocarcinoma after 2014 and consistent with the evolution of National Comprehensive Cancer Network (NCCN) guidelines. Benefits for chemotherapy are suggested after 2014 in the treatment of men with metastatic adenocarcinoma. The use of chemotherapy for neuroendocrine carcinoma at diagnosis has remained stable, and outcomes have improved in more recent years. Further development and optimization of chemotherapy continues to evolve for men with de novo diagnosis of metastatic prostate cancer.

Impact of discrimination and coping on Veterans' willingness to seek treatment for physical and mental health problems.

OBJECTIVE: This study aimed to provide insight into health disparities among Veterans by (a) documenting the prevalence of physical and mental health problems in a racially diverse sample of Veterans, (b) comparing Veterans' willingness to seek treatment for various physical and mental health conditions, and (c) examining the impact of discrimination and coping on willingness to seek treatment. METHOD: Veterans reported on current physical and mental health symptoms and the importance of treatment for various health conditions. Patterns were examined in the full sample (N = 334, 32% female) and the subsample who reported hazardous alcohol use in the past year (n = 116, 33% female). Linear regression was used to test alternative coping as a moderator of the association between experiences with discrimination and willingness to seek treatment among Veterans of color (n = 242, 37% female). RESULTS: Participants reported greater willingness to seek treatment for physical than mental health conditions. Sleep problems (75%) and substance use (74%) were the most prevalent health behaviors, but they were rated lowest in treatment importance. Among Veterans of color, everyday experiences with discrimination were generally associated with less willingness to seek physical or mental health treatment, but often only among those who denied use of coping strategies. CONCLUSIONS: Veterans are least willing to seek treatment for the health conditions that are most prevalent in their communities. Coping strategies may mitigate the negative association between discriminatory experiences and willingness to seek treatment among Veterans of color. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782.

BACKGROUND: The treatment for prostate cancer patients with biochemical failure after local therapy remains controversial. Peripheral androgen blockade using a combination of a 5-alpha reductase inhibitor and an antiandrogen may allow control of the prostate-specific antigen (PSA). Because testosterone levels are not suppressed, this approach may be associated with less morbidity than conventional gonadal androgen suppression. METHODS: All patients had undergone previous definitive local therapy and had evidence of a rising PSA >1ng/mL, with no evidence of recurrent disease. Patients received both finasteride, 5 mg orally per day, and flutamide, 250 mg orally 3× a day. Patients were followed for a PSA response and quality of life assessment. RESULTS: Ninety-nine of 101 accrued patients were eligible. A ≥80% PSA decline was seen in 96 (96%) patients. The median time to PSA progression was 85 months. With a median follow-up of 10 years, the median survival time had not been reached, and the 5-year overall survival rate was 87%. Toxicity was mild, with 18 patients stopping for toxicity; 15 had diarrhea, 4 had gynecomastia, and 3 had transaminase elevation. Baseline Functional Assessment of Cancer Therapy Prostate Module and Treatment Outcome Index scores decreased by 5 points each at 6 months after enrollment. CONCLUSIONS: The use of the finasteride/flutamide combination is feasible, and results in PSA declines of ≥80% in 96% of patients with serologic progression after definitive local therapy. There were no unexpected toxicities, and the change in quality of life was mild. Further evaluation of this or a similar regimen in a controlled clinical trial is warranted.

A phase 1 study of KOS-862 (Epothilone D) co-administered with carboplatin (Paraplatin®) in patients with advanced solid tumors.

PURPOSE: To determine the maximally tolerated dose (MTD) and pharmacokinetics of carboplatin plus KOS-862 (Epothilone D) a novel cytotoxic macrolide capable of causing mitotic arrest, in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: Patients who have progressed on standard regimens were treated at four different levels of KOS-862(mg/m(2))/Carboplatin(AUC): 50/5,75/5, 75/6 and 100/6 in a "3 + 3" phase I study study design to determine MTD. Patients received KOS-862 on Days 1 and 8, and carboplatin on day 1, of 3-week cycles. Pharmacokinetics of KOS-862 and Carboplatin were studied. RESULTS: Twenty-seven patients enrolled in the study. At the top dose level, 2 out of the 9 patients experienced Dose Limiting Toxicity. (grade 3 peripheral motor neuropathy in both patients) Twenty-seven patients had sufficient plasma data points for pharmacokinetic analysis Both the parent drug, KOS-862, and the major inactive metabolite Seco-D KOS-862 (KOS-1965) were quantified in plasma. Kinetics of KOS-862 were the same as seen in monotherapy studies using the same route and time of administration. Two patients had tumor response after study treatment. Ten of 20 evaluable patients had stable disease after 2 cycles of study treatment. The MTD in the present study was KOS-862 100 mg/m(2) + carboplatin AUC = 6. CONCLUSIONS: The pharmacokinetics of KOS-862 were similar in this combination study to those seen in previous monotherapy studies using the same route and time of administration. We have described the MTD of this schedule. The neurotoxicity seen with this regimen should be considered prior to its administration in unselected populations.

Aspects of the biology of Galaxias maculatus.

The biology of three landlocked and a riverine population of Galaxias maculatus were examined in western Victoria, Australia. All systems supported reproducing populations of these fish, including Lake Corangamite which had salinities that on occasion reached 82. Spawning sites in Lake Corangamite were located in adjacent tributaries and not in the main lake as was the case for other populations. The smallest fish were found in the fresh water Lake Purrumbete and the largest in the hypersaline Lake Corangamite. The size at which 50% of the population attained sexual maturity varied across sites, with fish maturing at a smaller size in Lake Purrumbete, followed by the Merri River, Lake Bullen Merri and Lake Corangamite. Condition was higher in the freshwater Lake Purrumbete and there was no relationship between condition and temperature, conductivity, turbidity and pH; but there was a positive relationship between condition and dissolved oxygen. Length frequency analysis suggested that the majority of fishes live for a year.