Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial.

BACKGROUND: Chronic pain negatively affects sleep; it is unclear whether pain relief from acupuncture contributes to sleep quality improvements in cancer survivors. This study aimed to evaluate the effect of acupuncture versus usual care on sleep quality among cancer survivors with comorbid sleep disturbance and chronic musculoskeletal pain. METHODS: Sleep outcome data from the Personalized Electroacupuncture Versus Auricular Acupuncture Comparative Effectiveness (PEACE) randomized clinical trial were analyzed. Electroacupuncture or auricular acupuncture was compared with usual care for sleep quality improvement over 10 weeks of treatment among cancer survivors with clinically significant sleep disturbance and chronic musculoskeletal pain at baseline. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) global score. RESULTS: Among 268 participants (mean [standard deviation (SD)] age, 61.4 [12.6] years; 191 women [71.3%]; mean [SD] baseline PSQI global score, 10.3 [3.3] points), electroacupuncture and auricular acupuncture resulted in greater reductions in the PSQI global score from baseline to 10 weeks in comparison with usual care: 1.42 points (95% confidence interval [CI], 0.45-2.38; p = .004) and 1.59 points (95% CI, 0.62-2.55; p = .001), respectively. The improvement in sleep quality for the acupuncture groups was sustained for 24 weeks from randomization. Furthermore, a greater proportion of patients in the electroacupuncture and auricular acupuncture groups had clinically meaningful improvement in sleep quality compared to the usual care group (41.0% and 42.9% vs. 21.4%; p = .044). CONCLUSIONS: Among cancer survivors with comorbid sleep disturbance and chronic pain, electroacupuncture and auricular acupuncture produced a clinically relevant and persistent improvement in sleep quality. These findings suggest that acupuncture may be an evidence-based nonpharmacologic intervention to improve sleep health for cancer survivors with pain. PLAIN LANGUAGE SUMMARY: This study analyzed the sleep quality data from a published randomized clinical trial that evaluated the effect of electroacupuncture or auricular acupuncture versus usual care on pain relief among people who survived cancer. This analysis included a prespecified subgroup of 268 participants with co-occurring sleep disturbance and chronic musculoskeletal pain at baseline and found that patients who used acupuncture for pain relief demonstrated greater improvements in sleep quality compared with patients who received usual care. Sleep quality improvement by acupuncture was sustained after the treatment ended.

Patient Characteristics Associated With Chemotherapy-Induced Peripheral Neuropathy Severity in a Phase II Clinical Trial: A Retrospective Analysis.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) can lead to chemotherapy dose reduction, delay, and discontinuation, and has limited effective prevention strategies. Our study aimed to identify patient characteristics associated with CIPN severity during weekly paclitaxel chemotherapy in people with early-stage breast cancer. METHODS: We retrospectively collected baseline data including participants' age, gender, race, body mass index (BMI), hemoglobin (regular and A1C), thyroid stimulating hormone, Vitamins (B6, B12, and D), anxiety, and depression up to 4 months prior to their first paclitaxel treatment. We also collected CIPN severity by Common Terminology Criteria for Adverse Events (CTCAE) after chemotherapy, chemotherapy relative dose density (RDI), disease recurrence, and mortality rate at the time of the analysis. Logistic regression was used for statistical analysis. RESULTS: We extracted 105 participants' baseline characteristics from electronic medical records. Baseline BMI was associated with CIPN severity (Odds Ratio [OR] 1.08; 95% CI, 1.01-1.16, P = .024). No significant correlations were observed in other covariates. At median follow-up (61 months), there were 12 (9.5%) breast cancer recurrences and six (5.7%) breast cancer-related deaths. Higher chemotherapy RDI was associated with improved disease-free survival (DFS, OR 1.025; 95% CI, 1.00-1.05; P = .028). CONCLUSIONS AND RELEVANCE: Baseline BMI may be a risk factor for CIPN and suboptimal chemotherapy delivery due to CIPN may negatively impact disease-free survival in patients with breast cancer. Further study is warranted to identify mitigating lifestyle factors to reduce incidences of CIPN during breast cancer treatment.

The relationship between anxiety and vaginal-related sexual health in postmenopausal breast cancer survivors on aromatase inhibitors therapies: a cross sectional study.

PURPOSE: Sexual health problems and anxiety are disruptive symptoms in breast cancer survivors; however, little is known about these symptoms in postmenopausal breast cancer survivors on aromatase inhibitors therapies. This study aimed to determine the relationship between anxiety and vaginal-related sexual health problems in this population. METHODS: We analyzed cross-sectional data from a cohort study of postmenopausal women breast cancer survivors receiving aromatase inhibitors. Vaginal-related sexual health problems were assessed with the Breast Cancer Prevention Trial Symptom Checklist. Anxiety was assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale. We used multivariable logistic regression to evaluate relationship between anxiety and vaginal-related sexual health adjusted for clinical and sociodemographic variables. RESULTS: Among 974 patients, 305 (31.3%) reported anxiety and 403 (41.4%) had vaginal-related sexual health problems. Compared to those without anxiety, patients with borderline and clinically abnormal anxiety reported higher rates of vaginal-related sexual health problems (36.8% vs. 49% and 55.7% respectively, p < 0.001). In multivariate analyses adjusted for clinical and sociodemographic factors, abnormal anxiety was associated with a higher rate of vaginal-related sexual health problems, with adjusted odds ratios of 1.69 (95% CI 1.06-2.70, p = 0.03). Vaginal-related sexual health problems were more frequent among patients who were under 65 years of age, received Taxane-based chemotherapy, reported depression, and were married/living with a partner (p < 0.05). CONCLUSION: Among postmenopausal breast cancer survivors on aromatase inhibitors therapies, anxiety was significantly associated with vaginal-related sexual health problems. As treatments for sexual health problems are limited, results suggest that psychosocial interventions for anxiety could potentially be adapted to simultaneously address sexual health needs.

Feasibility of combining pelvic reconstruction with gynecologic oncology-related surgery.

INTRODUCTION AND HYPOTHESIS: At our institution, every patient seen by the gynecologic oncology service is screened for pelvic floor dysfunction. This study was aimed at determining if a combined surgical approach by gynecologic oncology and urogynecology services at our institution was feasible and safe for this patient population. METHODS: We performed a retrospective review of patients undergoing combined surgery by gynecologic oncology and urogynecology services at our institution from 2013 to 2021. Perioperative variables, postoperative adverse events, and long-term outcomes were assessed, and descriptive statistics were performed. RESULTS: From 20 December 2013 to 29 January 2021, a total of 102 patients underwent concurrent surgical repair of pelvic organ prolapse and/or stress urinary incontinence. Seventy-three patients (71.6%) had normal/benign pathologic conditions, and 29 (28.4%) had premalignant/malignant pathologic conditions. Ten patients (9.8%) had a postoperative complication, including reoperation for exposed midurethral sling (4.9%), urinary retention requiring midurethral sling release (2.9%), reoperation for hemoperitoneum (1.0%), and anemia requiring blood transfusion (1.0%). Nine complications occurred in patients with benign/normal pathologic conditions (12.3%), and one complication occurred in patients with pre-malignant/malignant pathologic conditions (3.4%). CONCLUSIONS: In our single-institution experience, concurrent gynecologic oncology and pelvic floor reconstructive surgery were safe and feasible in combination with no reported major morbidity events.

Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study.

BACKGROUND: The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC. METHODS: ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone-prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone-prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov, number NCT02257736. FINDINGS: 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone-prednisone; 490 to abiraterone-prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0-28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4-27·4) in the apalutamide plus abiraterone-prednisone group versus 16·6 months (13·9-19·3) in the abiraterone-prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58-0·83; p<0·0001). At the updated analysis (final analysis for overall survival; median follow-up 54·8 months [IQR 51·5-58·4]), median radiographic progression-free survival was 24·0 months (95% CI 19·7-27·5) versus 16·6 months (13·9-19·3; HR 0·70, 95% CI 0·60-0·83; p<0·0001). The most common grade 3-4 treatment-emergent adverse event was hypertension (82 [17%] of 490 patients receiving apalutamide plus abiraterone-prednisone and 49 [10%] of 489 receiving abiraterone-prednisone). Serious treatment-emergent adverse events occurred in 195 (40%) patients receiving apalutamide plus abiraterone-prednisone and 181 (37%) patients receiving abiraterone-prednisone. Drug-related treatment-emergent adverse events with fatal outcomes occurred in three (1%) patients in the apalutamide plus abiraterone-prednisone group (2 pulmonary embolism, 1 cardiac failure) and five (1%) patients in the abiraterone-prednisone group (1 cardiac failure and 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death). INTERPRETATION: Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone-prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC. FUNDING: Janssen Research & Development.

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis.

INTRODUCTION: Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. METHODS: MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. RESULTS: A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. DISCUSSION: CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Characterization of chemotherapy-induced peripheral neuropathy using patient-reported outcomes and quantitative sensory testing.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect in cancer survivors. This study aimed to assess the characteristics of quantitative sensory testing (QST) and its correlation with patient-reported outcomes (PROs) in cancer patients with and without CIPN. METHODS: We conducted a cross-sectional analysis using baseline data from two clinical trials in solid tumor cancer survivors with no CIPN symptoms rated < 2 on a 0-10 Numerical Rating Scale (NRS) or moderate-to-severe CIPN rated ≥ 4 on the NRS. We collected PROs (NRS, Neuropathic Pain Scale, and Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity subscale at baseline. QST [Tactile Threshold (TT), Vibration Threshold (VT), Thermal Threshold (THT)] measurements were used to assess sensory fiber function; they were compared between patients with and without CIPN using Wilcoxon rank-sum tests. We used Spearman correlation coefficients to estimate associations between PROs and QST in all patients. RESULTS: Among 116 participants with CIPN (median NRS 5.00) and 10 participants without CIPN (median NRS 0.00), the median (interquartile range) TT was 3.84 (3.47, 4.12) and 3.53 (3.00, 3.84) in feet, respectively (p = 0.043). The median VT was 17.90 (9.42, 26.95) and 7.73 (5.94, 11.11) in feet, respectively (p = 0.001). Thermal cool threshold was 30.00 °C (28.90, 30.57) and 30.67 °C (30.57, 30.93), respectively (p = 0.007). Correlation coefficients between PROs and QST measures ranged between 0.02 and 0.50 in absolute magnitude. CONCLUSION: Patients with moderate-to-severe CIPN had significantly impaired tactile, vibratory, and thermal thresholds compared to patients without CIPN. QST correlates with PROs, suggesting CIPN symptom severity may correspond to sensory fiber functionality. QST may be incorporated into future CIPN research.

Understanding the Role and Value of Process Quality Indicators in Older Vascular Surgery Inpatients.

BACKGROUND: Despite the development of geriatrics surgery process quality indicators (QIs), few studies have reported on these QIs in routine surgical practice. Even less is known about the links between these QIs and clinical outcomes, and patient characteristics. We aimed to measure geriatrics surgery process QIs, and investigate the association between process QIs and outcomes, and QIs and patient characteristics, in hospitalized older vascular surgery patients. METHODS: This was a prospective cohort study of 150 consecutive patients aged ≥ 65 years admitted to a tertiary vascular surgery unit. Occurrence of geriatrics surgery process QIs as part of routine vascular surgery care was measured. Associations between QIs and high-risk patient characteristics, and QIs and clinical outcomes were assessed using clustered heatmaps. RESULTS: QI occurrence rate varied substantially from 2% to 93%. Some QIs, such as cognition and delirium screening, documented treatment preferences, and geriatrician consultation were infrequent and clustered with high-risk patient characteristcs. There were two major process-outcome clusters: (a) multidisciplinary consultations, communication and screening-based process QIs with multiple adverse outcomes, and (b) documentation and prescribing-related QIs with fewer adverse outcomes. CONCLUSIONS: Clustering patterns of process QIs with clinical outcomes are complex, and there is a differential occurrence of QIs by patient characteristics. Prospective intervention studies that report on implemented QIs, outcomes and patient characteristics are needed to better understand the causal pathways between process QIs and outcomes, and to help prioritize targets for quality improvement in the care of older surgical patients.

Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial.

BACKGROUND: In the interim analyses of the LATITUDE study, the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) led to a significant improvement in overall survival and radiographic progression-free survival compared with placebos plus ADT in men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (mCSPC). Here, we present long-term survival outcomes and safety of abiraterone acetate plus prednisone and ADT from the final analysis of the LATITUDE study. METHODS: This is a multicentre, randomised, double-blind, phase 3 trial done at 235 sites in 34 countries. Eligible patients (men aged ≥18 years) had newly diagnosed, histologically or cytologically confirmed prostate cancer with metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and at least two of the three high-risk prognostic factors (Gleason score of ≥8, presence of three or more lesions on bone scan, or presence of measurable visceral metastasis except lymph node metastasis). Patients were randomly assigned (1:1) to receive abiraterone acetate (1000 mg) once daily orally plus prednisone (5 mg) once daily orally and ADT (abiraterone acetate plus prednisone group) or matching placebos plus ADT (placebo group); each treatment cycle was 28 days. Randomisation was done by a centralised interactive web response system in a country-by-country scheme using permuted block randomisation, stratified by presence of visceral disease and ECOG performance status. The coprimary endpoint of overall survival was assessed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT01715285 and is complete. FINDINGS: Between Feb 12, 2013, and Dec 11, 2014, 1209 patients were screened, of whom ten were ineligible because of study site violations. 1199 patients were randomly assigned to either the abiraterone acetate plus prednisone group (n=597) or placebo group (n=602). After the results of the first interim analysis (cutoff date Oct 31, 2016), the study was unmasked to patients and investigators, and patients in the placebo group were allowed to cross over to receive abiraterone acetate and prednisone plus ADT treatment as per a protocol amendment (Feb 15, 2017) in an open-label extension phase of the study (up to 18 months from the protocol amendment). This final analysis (data cutoff Aug 15, 2018) was done after a median follow-up of 51·8 months (IQR 47·2-57·0) and 618 deaths (275 [46%] of 597 in the abiraterone acetate plus prednisone group and 343 [57%] of 602 in the placebo group). Overall survival was significantly longer in the abiraterone acetate plus prednisone group (median 53·3 months [95% CI 48·2-not reached]) than in the placebo group (36·5 months [33·5-40·0]), with a hazard ratio of 0·66 (95% CI 0·56-0·78; p<0·0001). The most common grade 3-4 adverse events were hypertension (125 [21%] in the abiraterone acetate plus prednisone group vs 60 [10%] in the placebo group vs three [4%] in the 72 patients who crossed over from placebo to abiraterone acetate plus prednisone) and hypokalaemia (70 [12%] vs ten [2%] vs two [3%]). Serious adverse events of any grade occurred in 192 (32%) of 597 patients in the abiraterone acetate plus prednisone group, 151 (25%) of 602 in the placebo group, and four (6%) of 72 in the crossover group. The most common treatment-related serious adverse event was hypokalaemia (four [1%] patients in the abiraterone acetate plus prednisone group and none in the other groups). Treatment-related deaths occurred in three (<1%) patients each in the abiraterone acetate plus prednisone group (gastric ulcer perforation, sudden death, and cerebrovascular accident) and the placebo group (sudden death, cerebrovascular accident, and pneumonia), with none in the crossover group. INTERPRETATION: The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with newly diagnosed high-risk mCSPC and had a manageable safety profile. These findings support the use of abiraterone acetate plus prednisone as a standard of care in patients with high-risk mCSPC. FUNDING: Janssen Research & Development.

Chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer survivors: a comparison of patient-reported outcomes and quantitative sensory testing.

PURPOSE: CIPN is a common, debilitating, and dose-limiting side effect of chemotherapy. Here, we describe characteristics of patients with CIPN using both patient-reported outcomes (PRO) and quantitative sensory testing (QST). METHODS: Breast cancer survivors with persistent moderate to severe CIPN defined by a rating of 4 or greater on a 0-10 Numeric Rating Scale (NRS) from two ongoing clinical trials were included. PROs included the Neuropathic Pain Scale (NPS) and Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx). QST included tactile and vibration detection threshold measurements. Data were analyzed using descriptive statistics and Spearman correlation coefficients. RESULTS: 49 female patients with a mean age of 61 years were assessed; 63% were Caucasian. Mean NRS scores were 4.2, 5.7, and 4.3 on 0-10 scale for pain, numbness, and tingling, respectively. Mean NPS score was 41.0 on a 0-100 scale, and the mean FACT/GOG-Ntx score was 25.8 on a 0-44 scale. QST showed mild to moderate impairments in tactile and vibration perception. The FACT/GOG-Ntx subscale for numbness was negatively correlated with tactile and vibration thresholds in both hands and feet (both p < 0.05). NPS was positively correlated with tactile thresholds in the hands and feet (p < 0.05). CONCLUSION: Patients with moderate to severe CIPN report moderate pain, numbness, and tingling, and exhibit reduced tactile and vibration perception on QST. Weak to moderate correlations were observed between PRO and QST. These data suggest that QST outcomes are associated with CIPN symptoms and may be useful in helping monitor and manage CIPN treatment.

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial.

BACKGROUND: In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL). METHODS: SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204. FINDINGS: Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8-26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group. INTERPRETATION: In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL. FUNDING: Janssen Research & Development.

Health Insurance Coverage among Young Adult Survivors of Pediatric Heart Transplantation.

OBJECTIVE: To describe the change in health insurance after heart transplantation among adolescents, and characterize the implications of this change for long-term transplant outcomes. STUDY DESIGN: Patients age 15-18 years receiving first-time heart transplantation between 1999 and 2011 were identified in the United Network for Organ Sharing registry and included in the analysis if they survived at least 5 years. The primary exposure was change or continuity of health insurance coverage between the time of transplant and the 5-year follow-up. Cox proportional hazards models were used to determine the association between insurance status change and long-term (>5 years) patient and graft survival. RESULTS: The analysis included 366 patients (age 16 ± 1 years at transplant), of whom 205 (56%) had continuous private insurance; 96 (26%) had continuous public insurance; and 65 (18%) had a change in insurance status. In stepwise multivariable Cox regression, change in insurance status was associated with greater mortality hazard, compared with continuous private insurance (hazard ratio = 1.9; 95% CI: 1.1, 3.2; P = .016), whereas long-term patient and graft survival did not differ between patients with continuous public and continuous private insurance. CONCLUSIONS: Continuity of insurance coverage is associated with improved long-term clinical outcomes among adolescent heart transplant recipients who survive into adulthood.

Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with chemotherapy, but researchers rarely study its risk factors, fall risk, and prevalence in long-term breast cancer survivors. We aimed to determine CIPN prevalence, risk factors, and association with psychological distress and falls among long-term breast cancer survivors. We conducted Cross-sectional analyses among postmenopausal women with a history of stage I-III breast cancer who received taxane-based chemotherapy. Participants reported neuropathic symptoms of tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We conducted multivariate logistic regression analyses to evaluate risk factors associated with the presence of CIPN and the relationship between CIPN and anxiety, depression, insomnia, and patient-reported falls. Among 296 participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with women of normal weight, being obese was associated with increased risk of CIPN (adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater insomnia severity, anxiety, and depression than those without (all p < 0.05). Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and 41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively, experiencing falls (p = 0.028). The majority of long-term breast cancer survivors who received taxane-based chemotherapy reported CIPN symptoms; obesity was a significant risk factor. Those with CIPN also reported increased psychological distress and falls. Interventions need to target CIPN and comorbid psychological symptoms, and incorporate fall prevention strategies for aging breast cancer survivors.

Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate.

BACKGROUND: Controversy exists over antidepressant use in bipolar II depression. AIMS: To compare the safety and effectiveness of antidepressantv.mood stabiliser monotherapy for bipolar type II major depressive episodes. METHOD: Randomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n= 65)v.lithium (n= 64) monotherapy in adult out-patients (trial registration numberNCT00602537). RESULTS: Primary outcome - venlafaxine produced a greater response rate (67.7%)v lithium (34.4%,P<0.001). Secondary outcomes - venlafaxine produced a greater remission rate (58.5%v 28.1%,P<0.001); greater decline in depression symptom scores over time (ß = -5.32, s.e. = 1.16, χ(2)= 21.19,P<0.001); greater reduction in global severity scores over time (ß = -1.05, s.e. = 0.22, w(2)= 22.33,P<0.001); and greater improvement in global change scores (ß = -1.31, s.e. = 0.32, χ(2)= 16.95,P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments. CONCLUSIONS: These findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium.

The Relationship Between Post-Migration Stress and Psychological Disorders in Refugees and Asylum Seekers.

Refugees demonstrate high rates of post-traumatic stress disorder (PTSD) and other psychological disorders. The recent increase in forcible displacement internationally necessitates the understanding of factors associated with refugee mental health. While pre-migration trauma is recognized as a key predictor of mental health outcomes in refugees and asylum seekers, research has increasingly focused on the psychological effects of post-migration stressors in the settlement environment. This article reviews the research evidence linking post-migration factors and mental health outcomes in refugees and asylum seekers. Findings indicate that socioeconomic, social, and interpersonal factors, as well as factors relating to the asylum process and immigration policy affect the psychological functioning of refugees. Limitations of the existing literature and future directions for research are discussed, along with implications for treatment and policy.

Arthralgia among women taking aromatase inhibitors: is there a shared inflammatory mechanism with co-morbid fatigue and insomnia?

INTRODUCTION: Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs. METHODS: Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations. RESULTS: Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (ß = 93.1; 95 % confidence interval (CI): 25.1-161.1; p = 0.008), eotaxin (ß = 79.9; 95 % CI: 32.5-127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (ß = 151.2; 95 % CI: 32.7-269.8; p = 0.013), and vitamin D-binding protein (VDBP) (ß = 19,422; 95 % CI: 5500.5-33,344; p = 0.006). CONCLUSIONS: Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.

Do attitudes and beliefs regarding complementary and alternative medicine impact its use among patients with cancer? A cross-sectional survey.

BACKGROUND: Complementary and alternative medicine (CAM) incorporates treatments used by cancer survivors in an attempt to improve their quality of life. Although population studies have identified factors associated with its use, to the best of the authors knowledge, assessment of why patients use CAM or the barriers against its use have not been examined to date. METHODS: The authors conducted a cross-sectional survey study in the thoracic, breast, and gastrointestinal medical oncology clinics at an academic cancer center. Clinical and demographic variables were collected by self-report and chart abstraction. Attitudes and beliefs were measured using the validated Attitudes and Beliefs about CAM (ABCAM) instrument. This instrument divides attitudes and beliefs into 3 domains: expected benefits, perceived barriers, and subjective norms. RESULTS: Among 969 participants (response rate, 82.7%) surveyed between June 2010 and September 2011, patient age ≤65 years, female sex, and college education were associated with a significantly greater expected benefit from CAM (P<.0001 for all). Nonwhite patients reported more perceived barriers to CAM use compared with white patients (P<.0001), but had a similar degree of expected benefit (P = .76). In a multivariate logistic regression analysis, all domains of the ABCAM instrument were found to be significantly associated with CAM use (P<.01 for all) among patients with cancer. Attitudes and beliefs regarding CAM explained much more variance in CAM use than clinical and demographic variables alone. CONCLUSIONS: Attitudes and beliefs varied by key clinical and demographic characteristics, and predicted CAM use. By developing CAM programs based upon attitudes and beliefs, barriers among underserved patient populations may be removed and more patient centered care may be provided.

Selecting danger signals: dissociable roles of nucleus accumbens shell and core glutamate in predictive fear learning.

Conditioned stimuli (CSs) vary in their reliability as predictors of danger. Animals must therefore select among CSs those that are appropriate to enter into an association with the aversive unconditioned stimulus (US). The actions of prediction error instruct this stimulus selection so that when prediction error is large, attention to the CS is maintained and learning occurs but when prediction is small attention to the CS is withdrawn and learning is prevented. Here we studied the role of glutamate acting at rat nucleus accumbens shell (AcbSh) and core (AcbC) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in this selection of danger signals. Using associative blocking and unblocking designs in rats, we show that antagonizing AcbSh AMPA receptors via infusions of 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX; 0.5 µg) prevents the unblocking of fear learning, whereas antagonizing AcbC AMPA receptors via infusions of NBQX (0.5 µg) prevents both the blocking and unblocking of fear learning. These results identify dissociable but complementary roles for AcbSh and AcbC glutamate acting at AMPA receptors in selecting danger signals: AcbSh AMPA receptors upregulate attention and learning to CSs that signal surprising USs, whereas AcbC AMPA receptors encode the predicted outcome of each trial.

Black breast cancer survivors experience greater upper extremity disability.

Over one-third of breast cancer survivors experience upper extremity disability. Black women present with factors associated with greater upper extremity disability, including: increased body mass index (BMI), more advanced disease stage at diagnosis, and varying treatment type compared with Whites. No prior research has evaluated the relationship between race and upper extremity disability using validated tools and controlling for these factors. Data were drawn from a survey study among 610 women with stage I-III hormone receptor positive breast cancer. The disabilities of the arm, shoulder and hand (QuickDASH) is an 11-item self-administered questionnaire that has been validated for breast cancer survivors to assess global upper extremity function over the past 7 days. Linear regression and mediation analysis estimated the relationships between race, BMI and QuickDASH score, adjusting for demographics and treatment types. Black women (n = 98) had 7.3 points higher average QuickDASH scores than White (n = 512) women (p < 0.001). After adjusting for BMI, age, education, cancer treatment, months since diagnosis, and aromatase inhibitor status, Black women had an average 4-point (95 % confidence interval 0.18-8.01) higher QuickDASH score (p = 0.04) than White women. Mediation analysis suggested that BMI attenuated the association between race and disability by 40 %. Even several years post-treatment, Black breast cancer survivors had greater upper extremity disability, which was partially mediated by higher BMIs. Close monitoring of high BMI Black women may be an important step in reducing disparities in cancer survivorship. More research is needed on the relationship between race, BMI, and upper extremity disability.