Causal impacts of smoking on pain conditions and the mediating pathways: a mendelian randomization study.

Smoking is a risk factor for multiple diseases. We performed mendelian randomization (MR) analyses to investigate the causal association of smoking initiation on pain conditions and the potential mediating pathways. Genetic associated with smoking initiation at the genome-wide significance level were selected as instrumental variables. Genetic associations with 10 pain conditions were derived from the FinnGen and UK Biobank study. Multivariable MR analysis was conducted to explore the mediation effects of depression, insomnia and sedentary behavior. A series of sensitivity analyses were conducted to assess the stability of our research findings. Genetic liability to smoking initiation was associated with an increased risk of angina pectoris, dorsalgia, low back pain, pain in limb, pain in joint, pain in thoracic spine and sciatica in both FinnGen and UK Biobank study. These causal associations were largely mediated by major depression (2.9- 39.5%), sedentary behavior (13.0- 31.2%), insomnia (10.3- 33.1%) and combination of all three mediators (30.2- 65.3%). The effects of smoking on outcomes were partly attenuated after adjusting for depression, sedentary behavior and insomnia respectively, and the direct effect of smoking initiation on pain was diminished toward null after adjusting for combined three mediators. These results were robust to sensitivity analyses. Our findings illustrated the causal effect of smoking and a broad range of pain conditions, and major depression, sedentary behavior and insomnia mediate many of these associations.

Applicability of a digital health application for cancer patients: a qualitative non-participation analysis.

BACKGROUND: The use of digital health applications (German acronym DiGA) for comprehensive patient care is increasing rapidly. Patients with non-organic insomnia can be prescribed an application to manage insomnia. Due to the high prevalence of insomnia in patients with cancer, we were interested in the effect of it and what barriers need to be overcome for its use. The focus of existing studies on acceptance and benefits prompted us to emphasise the analysis of barriers and thus to formulate possible solutions. METHODS: To analyse the barriers of use, the study population (patients with self-reported tiredness or sleep disturbance via validated instruments and cancer disease) was divided into 3 groups. In groups 1 (patients who refused to participate in advance) and 2 (patients who refused a prescription), short close-ended questionnaires were used for non-response assessment by treating oncologists. Problem-centred guidelines were used for the telephone interviews with group 3 (patients who did not provide information on DiGA use). Alternatively, group 3 was invited to complete and return the close-ended questionnaire. A quantitative analysis of the non-response reasons was conducted using SPSS in groups 1 and 2, while MAXQDA was used for the qualitative data in group 3. RESULTS: Patients refused to participate at several stages of our study. Quantitative data are available for groups 1 and 2. In the largest group 1, 62% of patients refused to participate due to non-subjective sleep disturbance (177 out of 189 patients) during recruitment by treating oncologists, despite high scores on the screening tool. In the small group 2 (11 out of 15), the most common reasons for withdrawal documented by the oncologists were loss of interest and deteriorating health. The problem-centred qualitative interviews with group 3 (17 patients) revealed that some of them used the prescribed DiGA, despite not being included in the main study and being categorized as lost to follow-up. CONCLUSION: Analysis of barriers to DiGA use showed that reducing administrative barriers and providing digital and personal support can increase acceptance of the use of DiGAs among cancer patients. Additionally, screening tools can act as a door opener to further communication regarding DiGAs. TRIAL REGISTRATION: German Register of Clinical Trials DRKS00034198, registration date: 7/05/24 (retrospectively registered).

Factors affecting poor sleep quality in last trimester pregnant women: a cross-sectional research from Turkey.

OBJECTIVE: The aim of the study was to determine the factors affecting poor sleep quality in the last trimester pregnant women. METHODS: A cross-sectional study was conducted at a tertiary care maternity hospital in Ankara, Turkey. The research was conducted between May and September 2019 with 570 pregnant women in the last trimester. The data were collected through the Personal Information Form, Pittsburgh Sleep Quality Index, International Physical Activity Questionnaire Short Form, Restless Legs Syndrome Form, Brief Fatigue Inventory, and Perceived Stress Scale. RESULTS: The mean Pittsburgh Sleep Quality Index score of the pregnant women was 5.98±3.31, and 48.9% of them were found to have over five Pittsburgh Sleep Quality Index scores. Hemoglobin levels, income perceptions, smoking habits, attending pregnant schools, experiencing leg pains or cramping, experiencing back, waist, or neck pains, Restless Legs Syndrome, fatigue levels, and perceived stress levels of the pregnant women were found to be important determinants of sleep quality (p<0.05). CONCLUSION: According to the findings, increasing hemogram levels, attending antenatal education programs, and improving the ability of pregnant women to manage stress are opportunities to improve sleep quality during pregnancy. Careful evaluation of pregnant women in terms of insomnia and affecting factors can be suggested during antenatal follow-up.

Causal relationship between insomnia and thyroid disease: A bidirectional Mendelian randomization study.

OBJECTIVE: Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). METHODS: We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)-Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. RESULTS: MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00-1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. CONCLUSION: This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.

The association between salivary IL-6 and poor sleep quality assessed using Apple watches in stressed workers in Japan.

Insomnia is a major concern among stressed workers worldwide. Although stress generally has a detrimental effect on sleep quality, the impact of biological stress, especially the immunological stress response, on sleep quality is not yet fully understood. Stressed workers were recruited through a screening process using a Brief Job Stress Questionnaire. The participants were asked to complete various occupation-related questionnaires. Additionally, saliva samples were collected to assess interleukin-6 (IL-6) levels as an immunological stress response. Subsequently, they were asked to wear an Apple Watch to record their sleep pattern for one week. Their sleep architecture was estimated using a previously published and validated method. Finally, data from 73 participants were analyzed. Our multivariable analysis revealed that shorter durations of slow-wave sleep (non-rapid eye movement sleep stage 3) were significantly associated with elevated IL-6 levels (p = 0.005) and greater daytime sleepiness (p = 0.002) after controlling for total sleep time. Our finding that a higher immunological stress response is associated with poor sleep quality contributes to a better understanding of insomnia in stressed workers and emphasizes the importance of stress management in this population.

Mediating effects of rumination on insomnia in cancer survivors: Influences of cancer-related fatigue, fear of recurrence, and psychological distress.

BACKGROUND: While advancements in cancer treatments have improved survival rates, they also lead to adverse effects such as insomnia, which significantly impacts survivors' sleep quality. OBJECTIVE: This study explores the influence of cancer-related fatigue (CRF), Fear of Cancer Recurrence (FCR), and psychological distress, with rumination serving as a mediating factor, on the insomnia experienced by cancer survivors. METHODS: The study involved 220 cancer survivors attending Shohada-e-Tajrish Hospital's oncology center in Tehran, Iran. Participants were selected through convenience sampling and completed several questionnaires: the Insomnia Severity Index, Fear of Cancer Recurrence Inventory, Cancer Fatigue Scale, Kessler Psychological Distress Scale, and Rumination Response Scale. RESULTS: The results showed that the tested model had a good fit, and the correlation matrix demonstrated significant positive correlations between CRF (0.46), FCR (0.15), psychological distress (0.55), and rumination (0.42) with insomnia in cancer survivors (p < 0.05). Notably, CRF (B = 0.356, p < 0.001) and psychological distress (B = 0.339, p < 0.001) affect insomnia both directly and indirectly through mediation by rumination, while the impact of FCR on insomnia was indirectly significant (B = 0.73, p < 0.05). CONCLUSION: The findings suggest that interventions focused on managing rumination could be potential targets to alleviate insomnia and improve the sleep quality of cancer survivors.

Iron Deficiency and Restless Sleep/Wake Behaviors in Neurodevelopmental Disorders and Mental Health Conditions.

Iron deficiency (ID) and restlessness are associated with sleep/wake-disorders (e.g., restless legs syndrome (RLS)) and neurodevelopmental disorders (attention deficit/hyperactivity and autism spectrum disorders (ADHD; ASD)). However, a standardized approach to assessing ID and restlessness is missing. We reviewed iron status and family sleep/ID history data collected at a sleep/wake behavior clinic under a quality improvement/quality assurance project. Restlessness was explored through patient and parental narratives and a 'suggested clinical immobilization test'. Of 199 patients, 94% had ID, with 43% having a family history of ID. ADHD (46%) and ASD (45%) were common conditions, along with chronic insomnia (61%), sleep-disordered breathing (50%), and parasomnias (22%). In unadjusted analysis, a family history of ID increased the odds (95% CI) of familial RLS (OR: 5.98, p = 0.0002, [2.35-15.2]), insomnia/DIMS (OR: 3.44, p = 0.0084, [1.37-8.64]), and RLS (OR: 7.00, p = 0.01, [1.49-32.93]) in patients with ADHD, and of insomnia/DIMS (OR: 4.77, p = 0.0014, [1.82-12.5]), RLS/PLMS (OR: 5.83, p = 0.009, [1.54-22.1]), RLS (OR: 4.05, p = 0.01, [1.33-12.3]), and familial RLS (OR: 2.82, p = 0.02, [1.17-6.81]) in patients with ASD. ID and restlessness were characteristics of ADHD and ASD, and a family history of ID increased the risk of sleep/wake-disorders. These findings highlight the need to integrate comprehensive blood work and family history to capture ID in children and adolescents with restless behaviors.

[Investigation on cognition for insomnia and preference for acupuncture in breast cancer survivors: a in-depth interview study].

OBJECTIVE: To understand the cognition for insomnia and preference for acupuncture in breast cancer survivors based on the in-depth interview. METHODS: Thirty breast cancer survivors with insomnia symptoms were collected for in-depth interview. The interview questions included three aspects, i.e. sleep expectation, cognition for insomnia (discomfort caused by insomnia, and underlying inducing factors of insomnia) and the preference for acupuncture (treatment methods used in the past, the reasons for not choosing acupuncture, and the tendency of acupuncture treatment). Using Colaizzi content analysis method, the data was analyzed. RESULTS: Regarding sleep expectation, most breast cancer survivors with insomnia symptoms were able to maintain normal activity in daytime. Insomnia symptoms often led to fatigue, and the inducing factors of insomnia referred to the treatment with endocrine therapy, anticipatory anxiety and inadequate sleep hygiene. All of the patients had received pharmacotherapy. The use proportion of non-pharmacological therapies was relatively low, and acupuncture was not chosen due to "not familiar with" and "fear of pain". Concerning to the preference for acupuncture, patients preferred the therapeutic methods of acupuncture with mild pain sensation and gentle stimulation; and the treatment should be more acceptable if delivered 2 or 3 times a week. CONCLUSION: Breast cancer survivors have the expectations for sleep, and are willing to receive the treatment with medication for their sleep disorders. Because of lack of the knowledge for acupuncture effect on insomnia and fear of strong needling sensation, a part of patients are unwilling to be treated with acupuncture therapy, but they are expected to receive the treatment with acupuncture while feeling more comfortable.

Voice-Activated Cognitive Behavioral Therapy for Insomnia: A Randomized Clinical Trial.

Importance: Insomnia symptoms affect an estimated 30% to 50% of the 4 million US breast cancer survivors. Previous studies have shown the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), but high insomnia prevalence suggests continued opportunities for delivery via new modalities. Objective: To determine the efficacy of a CBT-I-informed, voice-activated, internet-delivered program for improving insomnia symptoms among breast cancer survivors. Design, Setting, and Participants: In this randomized clinical trial, breast cancer survivors with insomnia (Insomnia Severity Index [ISI] score >7) were recruited from advocacy and survivorship groups and an oncology clinic. Eligible patients were females aged 18 years or older who had completed curative treatment more than 3 months before enrollment and had not undergone other behavioral sleep treatments in the prior year. Individuals were assessed for eligibility and randomized between March 2022 and October 2023, with data collection completed by December 2023. Intervention: Participants were randomized 1:1 to a smart speaker with a voice-interactive CBT-I program or educational control for 6 weeks. Main Outcomes and Measures: Linear mixed models and Cohen d estimates were used to evaluate the primary outcome of changes in ISI scores and secondary outcomes of sleep quality, wake after sleep onset, sleep onset latency, total sleep time, and sleep efficiency. Results: Of 76 women enrolled (38 each in the intervention and control groups), 70 (92.1%) completed the study. Mean (SD) age was 61.2 (9.3) years; 49 (64.5%) were married or partnered, and participants were a mean (SD) of 9.6 (6.8) years from diagnosis. From baseline to follow-up, ISI scores changed by a mean (SD) of -8.4 (4.7) points in the intervention group compared with -2.6 (3.5) in the control group (P < .001) (Cohen d, 1.41; 95% CI, 0.87-1.94). Sleep diary data showed statistically significant improvements in the intervention group compared with the control group for sleep quality (0.56; 95% CI, 0.39-0.74), wake after sleep onset (9.54 minutes; 95% CI, 1.93-17.10 minutes), sleep onset latency (8.32 minutes; 95% CI, 1.91-14.70 minutes), and sleep efficiency (-0.04%; 95% CI, -0.07% to -0.01%) but not for total sleep time (0.01 hours; 95% CI, -0.27 to 0.29 hours). Conclusions and Relevance: This randomized clinical trial of an in-home, voice-activated CBT-I program among breast cancer survivors found that the intervention improved insomnia symptoms. Future studies may explore how this program can be taken to scale and integrated into ambulatory care. Trial Registration: ClinicalTrials.gov Identifier: NCT05233800.

Temazepam or Melatonin Versus Placebo for the Treatment of Insomnia in Advanced Cancer: A Three-Arm, Double-Blind, Phase III, Multicenter, Randomized Clinical Trial.

Background: Sleep disturbance has a prevalence of 30-78% in patients with advanced cancer. While pharmacotherapy is common, randomized controlled studies (RCTs) investigating available agents are limited. This study examines the efficacy and safety of temazepam or melatonin versus placebo for sleep in advanced cancer. Methods: This is a multicenter, randomized, double-blind, placebo-controlled study of temazepam, melatonin prolonged release (PR) or placebo for insomnia in patients with advanced cancer, and an insomnia severity index (ISI) score of >11. Results: Twenty-one participants were randomized: nine to temazepam, eight to melatonin, and four to placebo. Baseline characteristics between groups were similar. The adjusted mean difference in day 8 ISI score versus placebo was -9.1 (95% confidence interval [CI] -17.5, 0.7, p = 0.04) for temazepam and -9.6 (95% CI -18,-1.2, p = 0.03) for melatonin PR. There was no improvement in global quality of life. Both agents were well tolerated. Conclusion: Temazepam and melatonin PR were associated with a clinically significant improvement in patient-reported insomnia severity compared with placebo. Findings need confirmation with larger patient numbers.

Racial differences in treatment adherence and response to acupuncture and cognitive behavioral therapy for insomnia among Black and White cancer survivors.

BACKGROUND: Racial disparities in sleep are well-documented. However, evidence-based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT-I) among Black and White cancer survivors. METHODS: We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT-I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co-morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants. RESULTS: Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all p < 0.05). Black survivors demonstrated lower adherence to CBT-I than White survivors (61.5% vs. 88.5%, p = 0.006), but their treatment response to CBT-I was similar to white survivors. Black survivors had similar adherence to acupuncture as white survivors (82.3% vs. 93.4%, p = 0.16), but they had greater reduction in insomnia severity with acupuncture (-3.0 points, 95% CI -5.4 to 0.4, p = 0.02). CONCLUSION: This study identified racial differences in sleep characteristics, as well as treatment adherence and responses to CBT-I and acupuncture. To address racial disparities in sleep health, future research should focus on improving CBT-I adherence and confirming the effectiveness of acupuncture in Black cancer survivors.

Trajectories of depression and predictors in lung cancer patients undergoing chemotherapy: growth mixture model.

BACKGROUND: Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. METHODS: In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. RESULTS: GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. CONCLUSIONS: Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.

Factors associated with hypnotics polypharmacy in the Japanese population.

OBJECTIVE: Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. METHODS: A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. RESULTS: Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01-9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74-0.87). CONCLUSIONS: Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy.

Exploring the Overlooked Depression, Anxiety, Insomnia and Fibromyalgia Syndrome Burden in Arab Women with Type 2 Diabetes: New Avenues for Chronic Disease Management.

Background and Objectives: Although physical health is always studied for women with diabetes, the mental health aspect is generally overlooked for this chronic disease. The present study aimed to examine the prevalence of psychosomatic symptoms, namely, fibromyalgia syndrome, depression, anxiety, and insomnia, and how these symptoms related to the medications used in a cohort of women diagnosed with type 2 diabetes (DM) in Jordan. Materials and Methods: This cross-sectional study recruited women diagnosed with type 2 diabetes, and validated scales (PSRS, PHQ-9, GAD-7, and ISI-A) for fibromyalgia syndrome, depression, anxiety, and insomnia were used. The associations between the different medications used and the dependent variables were examined using four separate multivariate logistic regression models. Results: Data were analyzed from 213 participants. Of them, 27.2% met the threshold for fibromyalgia syndrome diagnosis, 38% met the threshold for severe depression, 36.2% met the threshold for severe anxiety, and 39.9% met the threshold for severe insomnia. Fibromyalgia syndrome symptoms were significantly associated with glimepiride (OR = 1.92, CI = 1.00-3.68), ß-blockers (OR = 2.21, CI = 1.03-4.70), diuretics (OR = 3.13, CI = 1.26-7.78), herbal remedies (OR = 2.12, CI = 0.98-4.55), and prescriptions for centrally acting medication (OR = 2.78, CI = 1.24-6.29). Significant associations were found between depression and diuretics (OR = 2.62, CI = 1.05-6.67), over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 3.49, CI = 1.69-7.23), and herbal remedies (OR = 5.07, CI = 2.40-10.69). In addition, anxiety was significantly related to diuretics (OR = 2.48, CI = 1.02-6.02), and OTC NSAIDs (OR = 2.60, CI = 1.29-5.21). Significant associations were evident between insomnia and ß-blockers (OR = 3.23, CI = 1.51-6.95), acetaminophen (OR = 2.09, CI = 1.06-4.08), NSAIDs (OR = 4.61, CI = 2.18-9.76), and herbal remedies (OR = 5.95, CI = 2.71-13.07). Conclusions: Medications are associated with high burden of fibromyalgia syndrome, depression, anxiety, and insomnia. These findings underscore the importance of revising and optimizing the pharmacotherapy of these vulnerable patients, performing close mental health monitoring and the implementation of non-pharmacological interventions by integrating mental health services for women with chronic diseases such as diabetes.

Acute insomnia as the initial manifestation of Wilson' s disease: A Case Report.

BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive disease that causes impaired copper circulation and excretion. The initial manifestations of WD vary clinically, which makes early diagnosis very difficult. Sleep disorders have been described as common symptoms of WD, but the initial manifestations are in rare cases. CASE REPORT: This study aims to present a patient with acute insomnia as the initial manifestation of WD. Cranial magnetic resonance imaging showed extensive lesions in the bilateral putamen and caudate nucleus, pressure area of corpus callosum, midbrain, and pons. Interestingly, rare but characteristic signs of WD, such as "face of the giant panda," were shown in this case. WD diagnosis was further established by decreased ceruloplasmin level and ATP7B (adenosine-triphosphatase copper transporting beta polypeptide) gene mutations. CONCLUSIONS: We describe acute insomnia as the initial manifestation of WD in a 21-year-old male patient. Timely diagnosis allows for early copper-eliminating pharmacotherapy, which is of high prognostic importance, as the patient may be more responsive to treatment at this point.

Digital Cognitive-Behavioral Therapy for Insomnia in Cancer Survivors: Protocol for a Pragmatic Clinical Trial.

INTRODUCTION: Insomnia is one of the most prevalent, persistent, and distressing conditions associated with cancer, affecting almost half of all cancer survivors. Although cognitive-behavioral therapy for insomnia is well established as the gold-standard treatment for insomnia, its accessibility is very limited in routine care. We aim to examine the real-world effectiveness and acceptability of a digital cognitive-behavioral therapy for insomnia for cancer survivors with insomnia symptoms through a randomized controlled trial in Portugal. METHODS AND ANALYSIS: Our cancer trial will test the effects and acceptability of an accessible internet-delivered self-administered cognitive-behavioral therapy for insomnia digital intervention with clinician support, OncoSleep. This online program includes six interactive, personalized weekly sessions featuring evidence-based techniques targeting psychophysiological hyperarousal and maladaptive conditioning, tailored for cancer survivors. Research study procedures include screening for eligibility in the general population and randomization into one of two arms: the digital CBT-I program or a waitlist control group. Insomnia severity (primary outcome), fatigue, sleep diary outcomes, psychological distress, and quality of life (secondary outcomes) will be assessed at baseline and post-intervention.

Comparing sleep measures in cancer survivors: self-reported sleep diary versus objective wearable sleep tracker.

PURPOSE: Cancer survivors are increasingly using wearable fitness trackers, but it is unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group. METHODS: We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB), and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon signed rank test, Spearman's rank correlation coefficients, and the Mann-Whitney test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data. RESULTS: Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but there were no differences measured by Fitbit. CONCLUSIONS: TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.

Sedum kamtschaticum Exerts Hypnotic Effects via the Adenosine A2A Receptor in Mice.

Insomnia is a common sleep disorder with significant societal and economic impacts. Current pharmacotherapies for insomnia are often accompanied by side effects, necessitating the development of new therapeutic drugs. In this study, the hypnotic effects and mechanisms of Sedum kamtschaticum 30% ethanol extract (ESK) and one of its active compounds, myricitrin, were investigated using pentobarbital-induced sleep experiments, immunohistochemistry (IHC), receptor binding assays, and enzyme-linked immunosorbent assay (ELISA). The pentobarbital-induced sleep experiments revealed that ESK and myricitrin reduced sleep latency and prolonged total sleep time in a dose-dependent manner. Based on c-Fos immunostaining, ESK, and myricitrin enhanced the GABAergic neural activity in sleep-promoting ventrolateral preoptic nucleus (VLPO) GABAergic. By measuring the level of GABA released from VLPO GABAergic neurons, ESK and myricitrin were found to increase GABA release in the hypothalamus. These effects were significantly inhibited by SCH. Moreover, ESK exhibited a concentration-dependent binding affinity for the adenosine A2A receptors (A2AR). In conclusion, ESK and myricitrin have hypnotic effects, and their underlying mechanisms may be related to the activation of A2AR.

Acupuncture-related therapy for cancer-related insomnia: An overview of systematic reviews and meta-analysis.

BACKGROUND: The number of systematic reviews and meta-analyses (SRs/MAs) on acupuncture therapy for CRI is increasing; however, the credibility of the evidence remains unclear with controversial results, necessitating a comprehensive evaluation. OBJECTIVE: We aimed to critically assess the evidence in SRs/MAs regarding the effectiveness of acupuncture therapy for CRI from various aspects and conduct an exploratory analysis to identify potential issues. METHOD: Two reviewers conducted comprehensive searches in eight databases. SRs/MAs of randomized controlled trials are included. After screening according to inclusion and exclusion criteria, two reviewers extracted data from eligible SRs/MAs and conducted a detailed assessment of methodological quality, risk of bias, and quality of evidence using AMSTAR-2, ROBIS, and GRADE tools. Meanwhile, we calculated the Corrected Covered Area (CCA) leveraging the GROOVE tool. After manually excluding duplicate studies, we assess the risk of bias of primary studies extracted from SRs/MAs and conducted exploratory meta-analysis. RESULT: The comprehensive analysis included 10 SRs/MAs. The AMSRAT-2 results indicate significant methodological flaws in SRs/MAs, with the main issues focusing on the lack of provision of exclusion checklist for the studies. Furthermore, over half of the SRs/MAs have a high risk of bias due to incomplete retrieval and failure to follow the protocol. Most SRs/MAs demonstrated considerable completeness in reporting quality. Notably, the overall level of evidence is low. High overlap indicates redundant SRs/MAs. Exploratory analysis suggests that acupuncture therapy may be effective for CRI; however, with a high risk of bias, caution is needed in interpreting the results. Sensitivity analysis results are stable, and the funnel plot indicates no publication bias. Most SRs/MAs acknowledge the safety of acupuncture. CONCLUSION: Currently, the credibility of acupuncture therapy for treating CRI is low and improvements are needed in methodology, risk of bias, and quality of reporting. Acupuncture therapy shows potential but lacks sufficient support; high-level evidence is warranted to elucidate the effectiveness of acupuncture in treating CRI.

Older adults exercising ON TIME: protocol for a randomized controlled cross-over study to assess the effect of physical activity timing on insomnia severity.

BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function. METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock. DISCUSSION: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population. TRIAL REGISTRATION: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.