Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-label randomized phase 3 trial.

The clinical benefit of eribulin versus capecitabine was evaluated using health-related quality of life (HRQoL) data from a phase 3 randomized trial in patients with pretreated advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT00337103). The study population has been described previously (Kaufman et al. in J Clin Oncol 33:594-601, 2015). Eligible patients received eribulin (1.4 mg/m(2) intravenously on days 1 and 8) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14) per 21-day cycles. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 questions (QLQ-C30) and breast module-23 questions (QLQ-BR23), administered at baseline through 24 months, until disease progression or other antitumor treatment initiation. Minimally important difference (MID) and time to symptom worsening (TSW) were investigated. 1062 (96.4 %) Patients completed the EORTC questionnaire at baseline; overall, compliance was ≥80 %. Patients receiving capecitabine versus eribulin had significantly worse symptoms (higher scores) for nausea/vomiting (MID 8; P < 0.05) and diarrhea (MID 7; P < 0.05). Treatment with eribulin versus capecitabine, led to worse systemic therapy side-effects (dry mouth, different tastes, irritated eyes, feeling ill, hot flushes, headaches, and hair loss; MID 10; P < 0.01). Clinically meaningful worsening was observed for future perspective (MID 10; P < 0.05) with capecitabine and for systemic therapy side-effects scale (MID 10; P < 0.01) with eribulin. Patients receiving capecitabine experienced more-rapid deterioration in body image (by 2.9 months) and future perspective (by 1.4 months; P < 0.05) compared with those on eribulin; the opposite was observed for systemic side-effects where patients receiving eribulin experienced more-rapid deterioration than those receiving capecitabine (by 2 months; P < 0.05). Eribulin and capecitabine were found to have similar impact on patient functioning with no overall difference in HRQoL. Patients receiving eribulin reported worse systemic side-effects of chemotherapy but reduced gastrointestinal toxicity compared with capecitabine.

A Novel Approach to Computing Preference Estimates for Different Treatment Pathways: An Application in Oncology.

BACKGROUND: Patients with cancer may progress through multiple treatments with differing adverse effect profiles. Moreover, pathways may be fixed or flexible in allowing for escalation or de-escalation of treatment depending on interim outcomes. We sought to develop a methodology capable of estimating preferences for the entirety of a pathway involving a sequence of different treatments. METHODS: Patients with early breast cancer completed an online discrete choice experiment to assess preferences for eight key early breast cancer attributes. Hierarchical Bayesian modeling was used to calculate attribute-level preference weights. Preference weights for hypothetical pathways were estimated by summing the respective weights for efficacy, flexible or fixed pathway, duration, administration regimen, and adverse event risk, the last two of which were time-adjusted by multiplying each weight by the proportion of time spent on a selected treatment. RESULTS: Increases in the risk of a serious adverse event were most influential in treatment pathway preferences, followed by increases in efficacy and decreases in overall pathway duration. Patients preferred a flexible pathway versus a fixed pathway. Pathway preference estimates fluctuated in a logically consistent manner. Switching from a flexible to a fixed pathway yielded a significantly lower pathway preference. For this same pathway, when adjuvant treatment was replaced with a treatment with a more favorable toxicity profile and shorter duration, it offset the negative impact of the more toxic neoadjuvant chemotherapy. CONCLUSIONS: This novel methodology accounts for patient preference throughout a sequence of treatments, allowing for comparison of preferences across complex treatment pathways.

Military sexual trauma among homeless veterans.

BACKGROUND: Military sexual trauma (MST) is the Veteran Health Administration's (VHA) term for sexual assault and/or sexual harassment that occurs during military service. The experience of MST is associated with a variety of mental health conditions. Preliminary research suggests that MST may be associated with homelessness among female Veterans, although to date MST has not been examined in a national study of both female and male homeless Veterans. OBJECTIVE: To estimate the prevalence of MST, examine the association between MST and mental health conditions, and describe mental health utilization among homeless women and men. DESIGN AND PARTICIPANTS: National, cross-sectional study of 126,598 homeless Veterans who used VHA outpatient care in fiscal year 2010. MAIN MEASURES: All variables were obtained from VHA administrative databases, including MST screening status, ICD-9-CM codes to determine mental health diagnoses, and VHA utilization. KEY RESULTS: Of homeless Veterans in VHA, 39.7 % of females and 3.3 % of males experienced MST. Homeless Veterans who experienced MST demonstrated a significantly higher likelihood of almost all mental health conditions examined as compared to other homeless women and men, including depression, posttraumatic stress disorder, other anxiety disorders, substance use disorders, bipolar disorders, personality disorders, suicide, and, among men only, schizophrenia and psychotic disorders. Nearly all homeless Veterans had at least one mental health visit and Veterans who experienced MST utilized significantly more mental health visits compared to Veterans who did not experience MST. CONCLUSIONS: A substantial proportion of homeless Veterans using VHA services have experienced MST, and those who experienced MST had increased odds of mental health diagnoses. Homeless Veterans who had experienced MST had higher intensity of mental health care utilization and high rates of MST-related mental health care. This study highlights the importance of trauma-informed care among homeless Veterans and the success of VHA homeless programs in providing mental health care to homeless Veterans.

Characterization of a heat resistant beta-glucosidase as a new reporter in cells and mice.

BACKGROUND: Reporter genes are widely used in biology and only a limited number are available. We present a new reporter gene for the localization of mammalian cells and transgenic tissues based on detection of the bglA (SYNbglA) gene of Caldocellum saccharolyticum that encodes a thermophilic beta-glucosidase. RESULTS: SYNbglA was generated by introducing codon substitutions to remove CpG motifs as these are associated with gene silencing in mammalian cells. SYNbglA expression can be localized in situ or detected quantitatively in colorimetric assays and can be co-localized with E. coli beta-galactosidase. Further, we have generated a Cre-reporter mouse in which SYNbglA is expressed following recombination to demonstrate the general utility of SYNbglA for in vivo analyses. SYNbglA can be detected in tissue wholemounts and in frozen and wax embedded sections. CONCLUSIONS: SYNbglA will have general applicability to developmental and molecular studies in vitro and in vivo.

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis.

BACKGROUND: In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice. METHODS: This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor-positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events. RESULTS: Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93-8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67-11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%). CONCLUSION: Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status.

INTRODUCTION: Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer. METHODS: Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. RESULTS: Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group. CONCLUSION: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.

The family forum: directions for the implementation of family psychoeducation for severe mental illness.

It is well documented that family psychoeducation decreases relapse rates of individuals with schizophrenia. Despite the evidence, surveys indicate that families have minimal contact with their relative's treatment team, let alone participate in the evidence-based practice of family psychoeducation. The Department of Veterans Affairs (VA) sponsored a conference, the Family Forum, to assess the state of the art regarding family psychoeducation and to form a consensus regarding the next steps to increase family involvement. The forum reached consensus on these issues: family psychoeducation treatment models should be optimized by efforts to identify the factors mediating their success in order to maximize dissemination; leadership support, training in family psychoeducation models for managers and clinicians, and adequate resources are necessary to successfully implement family psychoeducation; because family psychoeducation may not be appropriate, indicated, or acceptable for all families, additional complementary strategies are needed that involve families in the mental health care of the patient; and work is required to develop and validate instruments that appropriately assess the intervention process and consumer and family outcomes. A treatment heuristic for working with families of persons with severe mental illness is also offered and provides a match of interventions at varying levels of intensity, tailored to family and consumer needs and circumstances. The article describes opportunities for the research and clinical communities to expand the proportion of families served.

Posttraumatic stress symptom change after family involvement in veterans' mental health care.

Research indicates that veterans would like their families to be more involved in their mental health care. While Department of Veteran Affairs (VA) policy requires certain providers to discuss veterans' interest in family involvement in their mental health care, no published studies have examined the associations between family involvement and mental health outcomes in routine VA mental health care. This study assessed posttraumatic stress disorder (PTSD) symptoms before and after veterans' first family session to test whether symptoms changed after family inclusion. The study used administrative data from VA medical records from 2008-2013. Veterans included in the present study sample had at least one assessment of PTSD symptoms in the year prior to and following their first family session (N = 6,107). Multilevel models tested whether PTSD symptoms changed over time. Moderator analyses assessed whether the change in PTSD symptoms differed depending on the veteran's gender, psychiatric comorbidities, and intensity of family involvement following the first session. On average, results showed statistically, but not clinically, significant reductions in PTSD symptoms after the first family session. Women veterans, veterans with comorbid depression, and those who had eight or more family sessions showed stronger symptom reductions than others. This study provides provisional evidence that family involvement is associated with PTSD symptom reduction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Military Sexual Trauma Among Recent Veterans: Correlates of Sexual Assault and Sexual Harassment.

INTRODUCTION: Military sexual trauma (MST) includes sexual harassment or sexual assault that occurs during military service and is of increasing public health concern. The population prevalence of MST among female and male veterans who served during Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) has not been estimated to our knowledge. The purpose of this study is to assess the population prevalence and identify military correlates of MST, sexual harassment, and sexual assault among OEF/OIF veterans. METHODS: MST was assessed in the 2009-2011 National Health Study for a New Generation of U.S. Veterans, a survey of 60,000 veterans who served during the OEF/OIF eras (response rate, 34%, n=20,563). Weighted prevalence estimates and AORs of MST, sexual harassment, and sexual assault among women and men were calculated. Gender-stratified logistic regression models controlled for military and demographic characteristics. Data analyses were conducted in 2013-2014. RESULTS: Approximately 41% of women and 4% of men reported experiencing MST. Deployed men had lower risk for MST compared with non-deployed men, though no difference was found among women. However, veterans reporting combat exposure during deployment had increased risk for MST compared with those without, while controlling for OEF/OIF deployment. Among women, Marines and Navy veterans had increased risk for MST compared with Air Force veterans. MST was significantly higher among veterans who reported using Veterans Affairs healthcare services. CONCLUSIONS: These prevalence estimates underscore the importance of public awareness and continued investigation of the public health impact of MST.

Vasomotor Symptoms and Quality of Life Among Veteran and Non-Veteran Postmenopausal Women.

INTRODUCTION: Vasomotor symptoms (VMS), including hot flashes and night sweats, are common among postmenopausal women and are associated with reduced health related quality of life (HRQOL). PURPOSE OF THE STUDY: To determine whether Veterans are more likely to report VMS than non-Veterans, and whether the association of VMS with HRQOL varies by Veteran status. DESIGN AND METHODS: We used data from the Women's Health Initiative Observational Study, including self-reported baseline VMS presence and severity, and HRQOL at follow-up Year 3 (RAND Short Form 36-Item Health Survey). Employing generalized linear models we estimated whether Veteran status was associated with any VMS. We estimated the association between any VMS and HRQOL using linear regression, stratified by Veteran status. Interaction terms were added separately to determine whether the association varied by baseline depression, obesity, or smoking status. RESULTS: The final analyses included 77,153 postmenopausal women (2,004 Veterans). After adjustment, Veterans were no more likely than non-Veterans to report any VMS at baseline (relative risk [RR] 0.97, 95% confidence interval [CI] 0.90-1.04) or moderate to severe VMS (RR 1.03, 95% CI 0.89-1.18). Any VMS was associated with decreased HRQOL at Year 3, particularly among Veterans (mean difference range: Veterans -2.7 to -4.6, p-values < .001; non-Veterans -2.2 to -2.6, 95% CI -0.13 to -0.09, p values < .001). Baseline depression and obesity, but not smoking, amplified the negative association between VMS and HRQOL. IMPLICATIONS: Multicondition care models for postmenopausal Veteran and non-Veteran women are needed that incorporate management strategies for VMS, weight, and depression.

Challenges in optimizing care in advanced breast cancer patients: Results of an international survey linked to the ABC1 consensus conference.

Until recently, many international guidelines have focussed on the treatment of early-stage breast cancer, with little emphasis on advanced-stage disease. To improve the management of advanced breast cancer (ABC), the European School of Oncology (ESO) established the ABC International Consensus Conference and Guidelines. Delegates from the first conference and additional groups selected by ESO were invited to complete a survey to identify current challenges and barriers associated with optimizing ABC management. 609 Respondents from 78 countries completed the questionnaire. "Lack of clear and applicable management guidelines" and "lack of high-level evidence for treatment options" were identified as key barriers to raising the profile of ABC and treating the disease. The survey also revealed a lack of multidisciplinary treatment, specialized ABC nurses, and routine psychosocial support in clinical practice. Implementing high-quality guidelines could lead to better practice in the management of ABC by encouraging multidisciplinary treatment and patient-support initiatives.

Systematic review of women veterans' mental health.

BACKGROUND: Given recent, rapid growth in the field of women veterans' mental health, the goal of this review was to update the status of women veterans' mental health research and to identify current themes in this literature. The scope of this review included women veterans' unique mental health needs, as well as gender differences in veterans' mental health needs. METHODS: Database searches were conducted for relevant articles published between January 2008 and July 2011. Searches were supplemented with bibliographic reviews and consultation with subject matter experts. FINDINGS: The database search yielded 375 titles; 32 met inclusion/exclusion criteria. The women veterans' mental health literature crosses over several domains, including prevalence, risk factors, health care utilization, treatment preferences, and access barriers. Studies were generally cross-sectional, descriptive, mixed-gender, and examined Department of Veterans Affairs (VA) health care users from all service eras. Results indicate higher rates of specific disorders (e.g., depression) and comorbidities, with differing risk factors and associated medical and functional impairment for female compared with male veterans. Although satisfaction with VA health care is generally high, unique barriers to care and indices of treatment satisfaction exist for women. CONCLUSIONS: There is a breadth of descriptive knowledge in many content areas of women veterans' mental health; however, the research base examining interventional and longitudinal designs is less developed. Understudied content areas and targets for future research and development include certain psychiatric disorders (e.g., schizophrenia), the effects of deployment on woman veterans' families, and strategies to address treatment access, attrition, and provision of gender-sensitive care.

Organizational factors associated with screening for military sexual trauma.

PURPOSE: This exploratory study investigated organizational factors associated with receipt of military sexual trauma (MST) screening during an early timeframe of the Veterans Health Administration's (VHA) implementation of the universal MST screening policy. METHODS: The sample consisted of all VHA patients eligible for MST screening in fiscal year 2005 at 119 VHA facilities. Analyses were conducted separately by gender and by user status (i.e., new patients to the VHA health care system in FY 2005 and continuing users who had previously used the VHA health care system in the past year). Multivariate generalized estimating equations were used to assess the effects of facility-level characteristics and adjusted for person-level covariates. RESULTS: Facility-level mandatory universal MST screening policies were associated with increased odds of receiving MST screening among new female patients and both continuing and new male patients: Odds ratio (OR), 2.87 (95% confidence interval [CI], 1.39-5.89) for new female patients; OR, 8.15 (95% CI, 2.93-22.69) for continuing male patients; and OR, 4.48 (95% CI, 1.79-11.20) for new male patients. Facility-level audit and feedback practices was associated with increased odds of receiving MST screening among new patients: OR, 1.91 (95% CI, 1.26-2.91) for females and OR, 1.86 (95% CI, 1.22-2.84) for males. Although the facility-level effect for women's health clinic (WHC) did not emerge as significant, patient-level effects indicated that among these facilities, women who used a WHC had greater odds of being screened for MST compared with women who had not used a WHC: OR, 1.79 (95% CI, 1.18-2.71) for continuing patients and OR, 2.20 (95% CI, 1.59-3.04) for new patients. CONCLUSION: This study showed that facility policies that promote universal MST screening, as well as audit and feedback practices at the facility, significantly improved the odds of patients receiving MST screening. Women veterans' utilization of a WHC was associated with higher odds of receiving MST screening. This study provides empirical support for the use of policies and audit and feedback practices which the VHA has used since the implementation of the MST screening directive to encourage compliance with VHA's MST screening policy and is likely associated with the present-day success in MST screening across all VHA facilities.