Studies of sex differences in the timing of human circadian rhythms have reported conflicting results. This may be because the studies conducted to date have not controlled for the masking effects of the rest activity cycle on the circadian rhythms being assessed. In the present analysis of data collected under controlled conditions, we examined sex differences in the timing of circadian rhythms while minimizing masking from behavioral and environmental factors using a constant routine (CR) protocol. All participants (28 women and 28 men paired by habitual wake time; age range, 18 30 years) maintained a regular self selected sleep wake schedule at home prior to the study. After 3 baseline days in the laboratory, participants began a CR. Women were found to have a signifi cantly higher melatonin amplitude and lower temperature amplitude than men. While sleep timing was the same between the 2 groups, the timing of the circa dian rhythms of core body temperature and pineal melatonin secretion was ear lier relative to sleep time in women as compared to men. Sleep therefore occurred at a later biological time for women than men, despite being at the same clock time. Given that sleep propensity and structure vary with circadian phase and are impacted by circulating melatonin, these findings may have important impli cations for understanding sex differences in sleep timing and duration, diurnal preference, and the prevalence of sleep disorders such as insomnia.

The human circadian pacemaker controls the timing of the release of the pineal hormone melatonin, which promotes sleep, decreases body temperature, and diminishes cognitive performance. Abnormal melatonin secretion has been observed in psychiatric and circadian disorders. Although melatonin secretion is directly suppressed by exposure to light in a nonlinear intensity-dependent fashion, little research has focused on the effect of prior photic history on this response. We examined eight subjects in controlled laboratory conditions using a within-subjects design. Baseline melatonin secretion was monitored under constant routine conditions and compared with two additional constant routines with a fixed light stimulus for 6.5 h of 200 lux (50 microW/cm(2)) after approximately 3 d of photic exposure during the subjective day of either about 200 lux (50 microW/cm(2)) or about 0.5 lux (0.15 microW/cm(2)). We found a significant increase in melatonin suppression during the stimulus after a prior photic history of approximately 0.5 lux compared with approximately 200 lux, revealing that humans exhibit adaptation of circadian photoreception. Such adaptation indicates that translation of a photic stimulus into drive on the human circadian pacemaker involves more complex temporal dynamics than previously recognized. Further elucidation of these properties could prove useful in potentiating light therapies for circadian and affective disorders.

Background In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known. Objectives To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans. Patients/Methods A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments. Results The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. VTE occurred in 327 (7.4%) patients within 1 year and occurred at a median of 77 days (interquartile range, 37‐153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6 months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18‐2.37). Patients in the post‐lenalidomide cohort with VTE had an increased mortality at both 6 months (aHR, 2.31; 95% CI, 1.52‐3.51) and 12 months (aHR, 1.66; 95% CI, 1.19‐2.33) after treatment initiation. Discussion This study shows that VTE during the first 6‐12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.

Background: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. Methods: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. Results: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84–0.96). Conclusions: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: The U.S. National Cancer Institute (NCI) developed software to collect symptomatic adverse events directly from patients participating in cancer clinical trials. This software administers surveys to patients using items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) via web-based or automated telephone interfaces, and enables management of survey administration and the resultant data by professionals (clinicians and research associates). Objective: The purpose of this study was to iteratively evaluate and improve the usability of the PRO-CTCAE software in both patients and professional users. Methods: Heuristic evaluation of software functionality was followed by semi-scripted, think-aloud protocols in sequential rounds of usability testing among patients, clinicians, and research associates. Patient testing was conducted both in clinic and remotely (i.e., from home) for both the web and telephone interfaces. Software was refined between rounds and retested. Results: Heuristic evaluation identified functionality problems and deviations from best practices across 10 standardized categories, which informed initial software improvement. Subsequently, user-based testing was conducted among 169 patients with cancer (54% female, 67% white, 26% high school education or less, 19% with limited computer experience, 18% older than 65), and 47 professionals (26% physicians, 26% nurses, 49% research associates) at three cancer centers in two rounds of usability testing. Software modifications between rounds addressed identified issues, including difficulty using radio buttons, absence of survey progress indicators, and login problems (for patients); and scheduling of patient surveys (for professionals). Following modifications, there were improvements in task performance for both patients and professional users. Conclusions: Software modifications, informed by rigorous assessment, rendered a usable system which is now in use in multiple NCI-sponsored multicenter cancer clinical trials. Clinical Trial: ClinicalTrials.gov Identifier: NCT01031641