Change in longitudinal trends in sleep quality and duration following breast cancer diagnosis: results from the Women's Health Initiative

Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women's Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis. To examine sleep duration, we fit a logistic regression model with random effects for both short (<6 h) and long (≥9 h) sleep. In addition, we studied the association between depressive symptoms and changes in WHIIRS and sleep duration. There was a significantly slower increase in the trend of WHIIRS after diagnosis (β = 0.06; p = 0.03), but there were non-significant increases in the trend of the probability of short or long sleep after diagnosis. The probability of depressive symptoms significantly decreased, though the decrease was more pronounced after diagnosis (p < 0.01). Trends in WHIIRS worsened at a relatively slower rate following diagnosis and lower depression rates may explain the slower worsening in WHIIRS. Our findings suggest that over a long period of time, breast cancer diagnosis does not adversely affect sleep quality and duration in postmenopausal women compared to sleep pre-diagnosis, yet both sleep quality and duration continue to worsen over time.WHI - National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]; Ohio State University Susan G Komen Graduate Trainee Program [GTDR15334082]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Work-Family Conflict and Employee Sleep: Evidence from IT Workers in the Work, Family and Health Study

Work-family conflict is a threat to healthy sleep behaviors among employees. This study aimed to examine how Work-to-Family Conflict (demands from work that interfere with one\u27s family/personal life; WTFC) and Family-to-Work Conflict (demands from family/personal life that interfere with work; FTWC) are associated with several dimensions of sleep among information technology workers. Employees at a U.S. IT firm (n = 799) provided self-reports of sleep sufficiency (feeling rested upon waking), sleep quality, and sleep maintenance insomnia symptoms (waking up in the middle of the night or early morning) in the last month. They also provided a week of actigraphy for nighttime sleep duration, napping, sleep timing, and a novel sleep inconsistency measure. Analyses adjusted for work conditions (job demands, decision authority, schedule control, and family-supportive supervisor behavior), and household and sociodemographic characteristics. Employees who experienced higher WTFC reported less sleep sufficiency, poorer sleep quality, and more insomnia symptoms. Higher WTFC also predicted shorter nighttime sleep duration, greater likelihood of napping, and longer nap duration. Furthermore, higher WTFC was linked to greater inconsistency of nighttime sleep duration and sleep clock times, whereas higher FTWC was associated with more rigidity of sleep timing mostly driven by wake time. Results highlight the unique associations of WTFC/FTWC with employee sleep independent of other work conditions and household and sociodemographic characteristics. Our novel methodological approach demonstrates differential associations of WTFC and FTWC with inconsistency of sleep timing. Given the strong associations between WTFC and poor sleep, future research should focus on reducing WTFC

Feasibility of implementing a text-based symptom-monitoring program of endometrial, ovarian, and breast cancer patients during treatment.

PurposeTo evaluate the feasibility of implementing systematic patient symptom monitoring during treatment using a smartphone.MethodsEndometrial [n = 50], ovarian [n = 70] and breast [n = 193] cancer patients participated in text-based symptom reporting for up to 12&nbsp;months. In order to promote equity, patients without a smartphone were provided with a device, with the phone charges paid by program funds. Each month, patients completed the Patient Health Questionnaire (PHQ-9), and 4 single items assessing fatigue, sleep quality, pain, and global quality of life during the past 7&nbsp;days rated on a 0 (low)&nbsp;-10 (high) scale. Patients' responses were captured using REDCap, with oncologists receiving monthly feedback. Lay navigators provided assistance to patients with non-medical needs.ResultsPatients utilizing this voluntary program had an overall mean age of 60.5 (range 26-87), and 85% were non-Hispanic white. iPhones were provided to 42 patients, and navigation services were used by 69 patients. Average adherence with monthly surveys ranged between 75-77%, with breast patients having lower adherence after 5&nbsp;months. The most commonly reported symptoms across cancer types were moderate levels (scores of 4-7) of fatigue and sleep disturbance. At 6&nbsp;months, 71-77% of all patients believed the surveys were useful to them and their health care team.ConclusionsWe established the feasibility of initiating and managing patients in a monthly text-based symptom-monitoring program. The provision of smartphones and patient navigation were unique and vital components of this program

The relationship between sleep and weight change among women diagnosed with breast cancer participating in the Women's Health Initiative

Short and long sleep duration and poor sleep quality are risk factors for weight gain and cancer mortality. The purpose of this study is to investigate the relationship between sleep and weight change among postmenopausal breast cancer survivors. Women participating in the Women's Health Initiative who were diagnosed with incident breast cancer between year one and year three were included. Self-reported sleep duration was categorized as ≤ 5 h (short), 6 h, 7-8 h (optimal), and ≥ 9 h (long). Self-reported sleep quality was categorized as poor, average, and above average. Post-diagnosis weight change was the difference of weight closest to, but preceding diagnosis, and year 3 weight. We used linear regression to evaluate sleep duration and sleep quality associations with post-diagnosis weight change adjusted for potential confounders. Among 1156 participants, 63% were weight stable after diagnosis; average weight gain post cancer diagnosis was 3.2 kg. Six percent of women reported sleeping ≤ 5 h, 26% reported 6 h, 64% reported 7-8 h, and 4% reported ≥ 9 h. There were no differences in adjusted estimates of weight change among participants with short duration (0.37 kg; 95% CI - 0.88, 1.63), or long duration (- 0.56 kg; 95% CI - 2.03, 0.90) compared to optimal duration, nor was there a difference among poor quality (- 0.51 kg; 95% CI - 1.42, 0.41) compared to above average quality. Among postmenopausal breast cancer survivors, sleep duration and quality were not associated with weight change after breast cancer diagnosis. Future studies should consider capturing change in adiposity and to expand beyond self-reported sleep

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

Purpose We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1 beta subunit of the cyclic AMP-dependent protein kinase A (PKA). Methods Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Results Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. Conclusion Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder

Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11

Growth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with a dominant human disease in a family with variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum associated with GDF11 variants and document the nature of the variants.We present a cohort of six probands with de novo and inherited nonsense/frameshift (4/6 patients) and missense (2/6) variants in GDF11. We generated gdf11 mutant zebrafish to model loss of gdf11 phenotypes and used an overexpression screen in Drosophila to test variant functionality.Patients with variants in GDF11 presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). gdf11 mutant zebrafish show craniofacial abnormalities and body segmentation defects that match some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants in our cohort are partial LOF variants.GDF11 is needed for human development, particularly neuronal development, and LOF GDF11 alleles can affect the development of numerous organs and tissues

Correction to: An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids (Genetics in Medicine, (2021), 23, 4, (740-750), 10.1038/s41436-020-01027-3)

In the original author list, Seth Perlman’s degrees were listed as MD, PhD. Dr Perlman’s degree is MD. The original version has been corrected