Concordance between self-reported sleep and actigraphy-assessed sleep in adult survivors of childhood cancer: the impact of psychological and neurocognitive late effects.

PURPOSE: To examine self-reported (30-day) sleep versus nightly actigraphy-assessed sleep concordance in long-term survivors of childhood cancer. METHODS: Four hundred seventy-seven participants enrolled in the St. Jude Lifetime Cohort (53.5% female, median (range) age 34.3 (19.3-61.6) years, 25.4 (10.9-49.3) years from diagnosis) completed the Pittsburgh Sleep Quality Index and ≥ 3 nights of actigraphy. Participants had neurocognitive impairment and/or a self-reported prolonged sleep onset latency (SOL). Self-reported 30-day sleep and nightly actigraphic sleep measures for sleep duration, SOL, and sleep efficiency (SE) were converted into ordinal categories for calculation of weighted kappa coefficients. General linear models estimated associations between measurement concordance and late effects. RESULTS: Agreements between self-reported and actigraphic measures were slight to fair for sleep duration and SOL measures (kw = 0.20 and kw = 0.22, respectively; p < 0.0001) and poor for SE measures (kw = 0.00, p = 0.79). In multivariable models, severe fatigue and poor sleep quality were significantly associated with greater absolute differences between self-reported and actigraphy-assessed sleep durations (B = 26.6 [p < 0.001] and B = 26.8 [p = 0.01], respectively). Survivors with (versus without) memory impairment had a 44-min higher absolute difference in sleep duration (B = 44.4, p < 0.001). Survivors with, versus without, depression and poor sleep quality had higher absolute discrepancies of SOL (B = 24.5 [p = 0.01] and B = 16.4 [p < 0.0001], respectively). Poor sleep quality was associated with a 12% higher absolute difference in SE (B = 12.32, p < 0.0001). CONCLUSIONS: Self-reported sleep and actigraphic sleep demonstrated discordance in our sample. Several prevalent late effects were statistically significantly associated with increased measurement discrepancy. Future studies should consider the impacts of late effects on sleep assessment in adult survivors of childhood cancer.

A randomized double-blind placebo-controlled trial of the effectiveness of melatonin on neurocognition and sleep in survivors of childhood cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors. METHOD: Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata. RESULTS: Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05). CONCLUSION: Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.

Short sleep duration and physical and psychological health outcomes among adult survivors of childhood cancer.

BACKGROUND: To examine associations between phenotypes of short sleep duration and clinically assessed health conditions in long-term survivors of childhood cancer. METHODS: Survivors recruited from the St. Jude Lifetime Cohort (n = 911; 52% female; mean age 34 years; 26 years postdiagnosis) completed behavioral health surveys and underwent comprehensive physical examinations. Sleep was assessed with the Pittsburgh Sleep Quality Index. Short sleep was defined as ≤6 h per night with phenotypes of short sleep including poor sleep efficiency (<85%), prolonged sleep onset latency (SOL; ≥30 min), and wake after sleep onset (≥3 times per week). Covariates included childhood cancer treatment exposures, demographics, body mass index, and physical inactivity. Separate modified Poisson regression models were computed for each health category to estimate relative risks (RR) and 95% confidence intervals (CI). Multinomial logistic regression models examined associations between sleep and an aggregated burden of chronic health conditions. RESULTS: Short sleep duration was reported among 44% (95% CI 41%-47%) of survivors. In multivariable models, short sleep duration alone was associated with pulmonary (RR = 1.35, 95% CI 1.08-1.69), endocrine (RR = 1.22, 95% CI 1.06-1.39) and gastrointestinal/hepatic conditions (RR = 1.46, 95% CI 1.18-1.79), and anxiety (RR 3.24, 95% CI 1.64-6.41) and depression (RR = 2.33, 95% CI 1.27-4.27). Short sleep with prolonged SOL was associated with a high/severe burden of health conditions (OR = 2.35, 95% CI 1.12-4.94). CONCLUSIONS: Short sleep duration was associated with multiple clinically ascertained adverse health conditions. Although the temporality of these associations cannot be determined in this cross-sectional study, sleep is modifiable and improving sleep may improve long-term health in survivors.

The Contribution of Stress and Distress to Cardiovascular Health in Adult Survivors of Childhood Cancer.

BACKGROUND: Childhood cancer survivors are at risk for cardiovascular morbidity and mortality that is not fully explained by cancer-directed therapies. We examined the contribution of emotional stress and distress to cardiac health in adult survivors of childhood cancer. METHODS: Participants included 3,267 adult survivors enrolled in the St. Jude Lifetime Cohort Study [median (range) 29.9 (18.1-64.5) years of age; 7.7 (0-24.8) years at diagnosis; 48.4% female]. Survivors completed comprehensive medical assessments and standardized measures of depression, anxiety, posttraumatic stress symptoms (PTSS), and perceived stress. Cardiovascular-related conditions included hypertension, diabetes, dyslipidemia, cardiomyopathy, dysrhythmia, myocardial infarction (severity graded 0-4), and metabolic syndrome (yes/no). Multivariable modified Poisson models examined associations between symptoms of stress/distress and cardiovascular outcomes. Longitudinal associations between stress/distress and new-onset cardiovascular outcomes, defined as a change from grade ≤1 at initial evaluation to grade ≥2 at follow-up (median 3.9 years) were examined in 1,748 participants. RESULTS: In multivariable cross-sectional models, stress/distress was associated with hypertension [risk ratio (RR) = 1.24; 95% confidence interval (CI), 1.07-1.43], dyslipidemia (RR = 1.29; 95% CI, 1.03-1.61), and metabolic syndrome (RR = 1.35; 95% CI, 1.17-1.54) independent of known cardiovascular risk factors. In longitudinal models, stress/distress was associated with new-onset dysrhythmia (RR = 2.87; 95% CI, 1.21-6.78), perceived stress with hypertension (RR = 1.42; 95% CI, 1.04-1.95), and PTSS and anxiety with dyslipidemia (RR = 1.72; 95% CI, 1.13-2.62; RR = 1.54; 95% CI, 1.01-2.35, respectively). CONCLUSIONS: Stress/distress is independently associated with adverse cardiovascular outcomes among childhood cancer survivors. IMPACT: Improving psychological health may serve as a potential intervention target for optimizing cardiac health among childhood cancer survivors.

Suicidality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Suicide is a serious public health concern. An increased risk of suicide ideation previously has been reported among survivors of childhood cancer. METHODS: Suicide mortality was assessed for all potentially eligible survivors (those aged ≥18 years who were ≥5 years after their cancer diagnosis; 7312 survivors). Risk factors for acute suicidal ideation were assessed among clinically evaluated survivors (3096 survivors) and the prevalence of acute ideation was compared with that of community controls (429 individuals). The prevalence of 12-month suicidality was assessed among survivors who could be compared with population data (1255 survivors). Standardized mortality ratios compared rates of suicide mortality among survivors with those of the general population. Risk ratios (RRs) and 95% confidence intervals (95% CIs) derived from generalized linear models identified risk factors associated with acute suicidal ideation. Standardized incidence ratios (SIRs) compared the prevalence of 12-month suicidality among survivors with that of a matched sample from the general population. RESULTS: Survivors reported a similar 12-month prevalence of ideation compared with the general population (SIR, 0.68; 95% CI, 0.35-1.01) and a lower prevalence of suicidal behaviors (planning: SIR, 0.17 [95% CI, 0.07-0.27]; attempts: SIR, 0.07 [95% CI, 0.00-0.15]) and mortality (standardized mortality ratio, 0.60; 95% CI, 0.34-0.86). Among survivors, depression (RR, 12.30; 95% CI, 7.89-19.11), anxiety (RR, 2.19; 95% CI, 1.40-3.40), and financial stress (RR, 1.47; 95% CI, 1.00-2.15) were found to be associated with a higher prevalence of acute suicidal ideation. CONCLUSIONS: Survivors of childhood cancer were found to be at a lower risk of suicidal behaviors and mortality, yet endorsed a prevalence of ideation similar to that of the general population. These results are in contrast to previous findings of suicidal ideation among survivors and support the need for further research to inform screening strategies and interventions. LAY SUMMARY: The purpose of the current study was to compare the risk of suicidal ideation, behaviors, and mortality in adult survivors of childhood cancer with those of the general population. Risk factors associated with suicidal ideation among survivors of childhood cancer also were examined. Survivors of childhood cancer reported a similar risk of ideation compared with the general population, but a lower risk of suicidal behaviors and mortality. Psychological health and financial stressors were found to be risk factors associated with suicidal ideation. Although adult survivors of childhood cancer did not report a greater risk of suicidality compared with the general population, psychosocial care in survivorship remains essential.

Insomnia and Neurocognitive Functioning in Adult Survivors of Childhood Cancer.

BACKGROUND: In noncancer populations, insomnia is known to affect neurocognitive processes. Although the prevalence of insomnia appears to be elevated in survivors of childhood cancer, relatively little is known about its association with neurocognitive performance in this at-risk population. METHODS: A total of 911 survivors (51.9% female; mean [SD] age, 34 [9.0] years; time since diagnosis, 26 [9.1] years) completed direct assessments of attention, memory, processing speed, and executive functioning and self-reported symptoms of sleep (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and daytime sleepiness (Epworth Sleepiness Scale). Sex-stratified general linear models were used to examine associations between insomnia and neurocognitive performance, with adjustment for treatment exposures and chronic health conditions. All statistical tests were two-sided. RESULTS: Insomnia was reported by 22.1% of females and 12.3% of males (P < .001). After adjustment for neurotoxic treatment exposures, insomnia (vs healthy sleepers with no daytime fatigue or sleepiness) was associated with worse neurocognitive performance in the domains of verbal reasoning, memory, attention, executive function, and processing speed (verbal reasoning: males ß = -0.34, P = .04, females ß = -0.57, P < .001; long-term memory: males ß = -0.60, P < .001, females ß = -0.36, P = .02; sustained attention: males ß = -0.85, P < .001, females ß = -0.42, P = .006; cognitive flexibility: males ß = -0.70, P = .002, females ß = -0.40, P = .02). Self-reported sleep disturbance without daytime fatigue or sleepiness or daytime fatigue or sleepiness alone were not consistently associated with poorer neurocognitive performance. CONCLUSIONS: Insomnia was highly prevalent and contributed to the neurocognitive burden experienced by adult survivors of childhood cancer. Treatment of insomnia may improve neurocognitive problems in survivors.

Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research.

BACKGROUND: Limited information is available about the representativeness of survivors engaging in patient-centered research, despite the potential for threats to generalizability. We thus aimed to assess the representativeness of survivors engaged or interested in research development. METHODS: We used data from the Health Information National Trends Survey, a nationally representative survey, to identify survivors of adult cancers. Our outcomes of interest were based on responses to questions about engagement or interest in developing patient-centered research. We estimated the ratio of relative frequencies (RRF) and corresponding 95% confidence limits (CL) of sociodemographic and survivorship characteristics between survivors engaged or interested in patient-centered research and the overall survivor population. RESULTS: Our study population comprised 934 survivors, of whom 5% reported being engaged in patient-centered research and 26% reported an interest in participating. Relative frequencies of characteristics were discordant for engaged survivors but largely similar for interested survivors compared with all survivors. In particular, engaged survivors had a higher relative frequency of individuals ages 50 to 64 years (RRF = 1.7; 95% CL, 1.1-2.5), Hispanic (RRF = 2.9; 95% CL, 1.2-6.9), non-Hispanic Black (RRF = 2.9; 95% CL, 1.1-2.5), and unemployment (RRF = 4.7; 95% CL, 1.4-16). CONCLUSIONS: We observed several meaningful differences in the characteristics of survivors engaged in patient-centered research compared with all survivors, which raises concerns about the generalizability of findings from such studies. IMPACT: Patient-centered research may not benefit the broader survivor community if survivors engaging in research development are not representative of all survivors. Greater attention to recruiting mechanisms is necessary to avoid creating disparities.

Sleep apnea and kidney transplant outcomes: findings from a 20-year (1997-2017) historical cohort study.

OBJECTIVE/BACKGROUND: A historic cohort single-center study of kidney transplant recipients with graft loss examined the associations between sleep apnea and two transplant outcomes, death with a functioning graft (DWFG), and graft survival time. PATIENT/METHODS: Adult patients who received transplants and experienced graft failure or DWFG from January 1, 1997 to January 1, 2017 constituted the cohort (n = 322). Data for the study were obtained by merging two secondary data sources: the Organ Procurement and Transplantation Network (OPTN) database and the transplant center's medical records. A Cox regression modeled the association of diagnosed sleep apnea, stratified by year-of transplant surgery, with graft survival time. Using backward elimination, this model was adjusted for recipient age, race/ethnicity, gender, functional status, donor age, and antigen mismatch. RESULTS: No statistically significant differences were found for proportions of DWFG in those with, versus without, sleep apnea, informing our censoring approach. When examining graft survival time, the Cox regression model was stratified given a sleep apnea and year-of-transplant interaction (p < 0.01, adjusted model). For patients transplanted between 1997 and 2008, sleep apnea was statistically significantly associated with a decreased risk of graft failure or cardiovascular-related DWFG [adjusted Hazard Ratio (aHR) = 0.63, 95%CI, 0.42-0.94]. For patients transplanted between 2009 and 2017, sleep apnea statistically significantly increased the risk of graft failure or cardiovascular-related DWFG (aHR = 2.61, 95%CI, 1.13-6.00). CONCLUSIONS: In a cohort of transplant recipients with graft loss, sleep apnea increased the risk of graft loss nearly three-fold among patients transplanted between 2009 and 2017. Similar DWFG proportions by sleep apnea presence indicate this risk is likely driven by renal failure, not mortality. Further research on whether treatment of sleep apnea can improve graft survival is warranted.