Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06–1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04–1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers

Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses

Objectives: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. Methods: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2). Conclusion: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.</p

Sleep and productivity benefits of digital cognitive behavioural therapy for insomnia: a randomised controlled trial conducted in the workplace environment

Objective: Evaluating digital Cognitive Behavioural Therapy (dCBT) for insomnia in a workplace environment. Methods: Within a randomized controlled trial in a Fortune 500 company, we randomized 270 self-identified poor sleepers [180M/90F: mean age 33.6y (23-56y)] to dCBT (n=135) or waiting list (WL, n=135). dCBT comprised 6 online sessions delivered by an animated therapist. Major assessments were at baseline and post-treatment. Results: Sleep Condition Indicator (SCI) scores were significantly higher for the dCBT group [interaction term: F(1,485) = 15.63, p&lt;.0001], representing Cohen’s d of 1.10 following dCBT (d=0.34 for WL). On the Work Productivity and Impairment questionnaire, ‘presenteeism’ demonstrated significant improvements following dCBT [F(1,485)=10.99, p=0.001: d =0.64 for dCBT, d =0.09 for WL]. Effects for ‘abseenteeism’ failed to reach statistical significance (p=0.101). Conclusions: dCBT is effective in improving sleep and work-based productivity in adults with insomnia. </p

Sleep disturbance and intrusive memories after presenting to the emergency department following a traumatic motor vehicle accident: an exploratory analysis

Background: Sleep disturbances are common after traumatic events and have been hypothesized to be a risk factor in the development of psychopathology such as that associated with posttraumatic stress disorder (PTSD). Objective: To assess the association between intrusive memories, a core clinical feature of PTSD, and self-reported sleep disturbance shortly after experiencing or witnessing a motor vehicle accident, and whether a brief behavioural intervention (trauma reminder cue and Tetris gameplay) reduced sleep disturbance post-trauma. Method: The exploratory analyses included 71 participants (mean age 39.66, standard deviation 16.32; 37 women, 52.1%) enrolled in a previously published proof-of-concept randomized controlled trial. Participants were recruited from the emergency department after experiencing or witnessing a traumatic motor vehicle accident. Intrusive memories were assessed with a daily paper-and-pen diary for one week post-trauma, and sleep disturbances with three questions from the Impact of Event Scale-Revised assessing problems initiating sleep, problems maintaining sleep and dreams about the event at one week and one month post-trauma. Missing data were imputed 15 times. Results: The total number of intrusive memories during the first week post-trauma suggested weak to moderate pooled intercorrelations with problems initiating and maintaining sleep. An ordinal regression using imputed data suggested that the intervention had no effect on sleep disturbances, while completers only analyses suggested an improvement in problems maintaining sleep at one week. Conclusions: This exploratory study suggested that experiencing early intrusive memories is related to sleep disturbances. Sleep disturbance might be a particularly important construct to assess in studies involving intrusive memories post-trauma