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Background: Chronic insomnia is among the most reported complaints of Veterans and military personnel referred for mental health services. It is highly comorbid with medical and psychiatric disorders, and is associated with significantly increased healthcare utilization and costs. Evidence-based psychotherapy, namely Cognitive Behavioral Therapy for Insomnia (CBTI), is an effective treatment and recommended over prescription sleep medications. While CBTI is part of a nationwide rollout in the Veterans Health Administration to train hundreds of providers, access to treatment is still limited for many Veterans due to limited treatment availability, low patient and provider knowledge about treatment options, and Veteran barriers such as distance and travel, work schedules, and childcare. Uptake of a briefer, more primary-care-friendly treatment into routine clinical care in Veterans Affairs (VA) primary care settings, where insomnia is typically first recognized and diagnosed, may effectively and efficiently increase access to effective insomnia interventions and help decrease the risks and burdens related to chronic insomnia.Methods: This hybrid type I trial is composed of two aims. The first preliminarily tests the clinical non-inferiority of Brief Behavioral Treatment for Insomnia (BBTI) versus the current "gold standard" treatment, CBTI. The second is a qualitative needs assessment, guided by the Consolidated Framework for Implementation Research (CFIR), to identify potential factors that may affect successful implementation and integration of behavioral treatments for insomnia in the primary care setting. To identify potential implementation factors, individual interviews are conducted with the Veterans who participate in the clinical trial, as well as VA primary care providers and nursing staff.Discussion: It is increasingly important to better understand barriers to, and facilitators of, implementing insomnia interventions in order to ensure that Veterans have the best access to care. Furthermore, it is important to evaluate the potential for new avenues of treatment delivery, like BBTI in the primary care setting, which can benefit Veterans who may not have adequate access to specialty mental health providers trained in CBTI.Trial Registration: ClinicalTrials.gov, ID: NCT02724800 . Registered on 31 March 2016. [ABSTRACT FROM AUTHOR]

Background: Drug-dependent insomnia refers to insomnia patients taking sedatives and sleeping pills regularly for a long period. Auricular acupressure (AA) has attracted growing attention as a complementary treatment for insomnia. Nevertheless, there is a lack of rigorous studies evaluating AA specifically for estazolam-dependent insomnia. Our proposed trial aims to assess the therapeutic effect of AA on estazolam-dependent insomnia. Methods: This study is a randomized, single-blinded, three-arm controlled trial. No less than 108 participants will be randomized into one of three groups: AA group, sham auricular acupressure (SAA) group, and conventional dosage reduction group. All treatments will be administered for 4 weeks, with a follow-up period of 1 month. The primary clinical outcomes will be estazolam dosing and reduction rates, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels. Secondary outcomes will concern the Pittsburgh sleep quality index (PSQI) and Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ). Both intention-to-treat and per-protocol analyses will be performed, with the significance level determined as 5%. Discussion: The study results will provide evidence on the efficacy and safety of AA in managing estazolam-dependent insomnia by analyzing its immediate effect, time-effect relationship, and reduction of estazolam use. Trial Registration: Clinicaltrials.gov (identification number: NCT06258226; Registered 5 February 2024, https://clinicaltrials.gov/ct2/show/NCT06258226). [ABSTRACT FROM AUTHOR]

Background: The neural cells in the brains of patients with Parkinson’s disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson’s disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson’s disease based on the central-peripheral-central theory. Methods: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson’s disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. Discussion: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. Trial registration: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023. [ABSTRACT FROM AUTHOR]

Background: Patients with mental disorders have a higher prevalence of sleep problems than the general population. Sleep problems may include insomnia, circadian rhythm disorders, or hypersomnia. A transdiagnostic approach combining cognitive behavioral therapy for insomnia (CBT-I) with chronotherapy addressing a broad range of sleep problems has shown promising results in a limited number of studies. The aim of the study is to investigate the efficacy of a transdiagnostic sleep intervention for patients with sleep problems comorbid to bipolar disorder, unipolar depression, or attention deficit disorders. The primary hypothesis is that the intervention improves sleep quality compared with a control group. The secondary hypotheses are that the intervention increases subjective and objective sleep efficiency, reduces sleep onset latency, wake after sleep onset, number of awakenings, and severity of insomnia; and that it improves well-being, personal recovery, work ability, and consumption of sleep medication compared with a control group. Methods: The study is a randomized controlled trial enrolling 88 outpatients with bipolar disorder, major depression, or attention deficit disorder with symptoms of various sleep problems (insomnia, circadian rhythm disorders, or hypersomnia). Patients are allocated to either an intervention group receiving six sessions of transdiagnostic sleep treatment or to a control group receiving a single session of sleep hygiene education. Assessments are made at baseline, at week two, and after 6 weeks in both groups. Actigraphy is performed continuously throughout the 6-week study period for all patients. The primary outcome is changes in the subjective appraisal of sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes are changes in sleep efficiency, sleep onset latency, wake after sleep onset, number of nocturnal awakenings (based on actigraph and sleep diary data), changes in insomnia severity (Insomnia Severity Index), well-being (WHO-5 Well-Being Index), personal recovery (INSPIRE-O), work ability (Work Ability Index), and consumption of sleep medication (sleep-diaries). Discussion: The study was initiated in 2022 and the inclusion period will continue until mid-2024. The results may have implications for the development and implementation of additional treatment options for patients with mental disorders and comorbid sleep problems. Trial registration: ClinicalTrials.gov. NCT05406414. Registered on June 6, 2022. [ABSTRACT FROM AUTHOR]

Background: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. Methods: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery–Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. Discussion: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. Trial registration: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0). https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L. [ABSTRACT FROM AUTHOR]

Background: Many elderly individuals who experience sleep disturbances would consider complementary and alternative medicine as an alternative therapeutic option in light of the limitations of traditional treatments. Mindfulness-based interventions (MBIs) and Tai Chi Chuan (TCC) are two alternative forms of complementary and alternative medicine. They both share the common feature of a focus on breathing but represent distinct approaches with different mechanisms and philosophical orientations. The trial described in this protocol aims to evaluate the effects of an integrated form of mindfulness-based Tai Chi Chuan (MBTCC) programme and the underlying mechanisms of the beneficial effects over a 12-month follow-up.Methods: The planned study is a four-armed randomized controlled trial with repeated measures. A total of 256 community-dwelling older adults with sleep problems will be recruited and randomized into four groups: (1) an MBTCC group, (2) an MBI group, (3) a TCC group, and (4) a sleep hygiene education (SHE) control group. The outcome measures in terms of insomnia severity, interoception, sleep-wake pattern, health status, rumination, and hyperarousal level will be collected at four time points: at baseline (T1), after the 8-week intervention (T2), 6 months after the intervention (T3), and 1 year after the intervention (T4). In addition, qualitative evaluation through focus group interviews will be conducted at the end of the 12-month assessment period (T4).Discussion: This trial will illuminate the synergetic effect of combining both MBIs and TCC on optimizing improvements in sleep disturbance. The findings from this study can provide empirical support for this integrated treatment, which provides an alternative for healthcare professionals in elderly service to select appropriate practices to treat elderly people with sleep disturbance. It can further help to lessen the growing public health burden of sleep disturbances among the elderly living in the community.Trial Registration: ClinicalTrials.gov . NCT05396092 . Published on 24 May 2022. [ABSTRACT FROM AUTHOR]

Background: The use of video games, a hobby for many teenagers in their leisure time, has brought with it a new potential for concerns. Internet gaming disorder (IGD) is a mental condition classified as a disorder due to addictive behaviors. It may include use of video games, both online and offline. Consequences of IGD may include introversion, social anxiety, mood swings, loneliness, sleep problems, behavioral problems, depression, low self-esteem, and increased violence. In order to design an app-based intervention for adolescents, a transtheoretical model (TTM) has been used. This widely used model in the field of behavioral change is also practical for health education programs. In addition, cognitive-behavioral therapy (CBT) has been used to make people more aware of their behaviors, feelings and thoughts and how to achieve behavioral change. The present study seeks to determine the effectiveness of this app-based intervention in in the treatment of IGD among adolescents.Method: In this single-blinded, randomized, controlled trial, 206 high-school adolescents aged 13 to 18 years in Qazvin city will be recruited. Eligible adolescents will be randomly assigned into intervention and control groups. Eight consecutive sessions delivered over 2 months and based on the TTM and CBT will be delivered through the `app (named HAPPYTEEN) to the intervention group. The control group will receive a sleep hygiene intervention (8 consecutive sessions for 2 months) via the app. Data collection tools include the Internet Gaming Disorder Scale, Insomnia Severity Index, Depression, Anxiety, and Stress Scales, Stages of Change Questionnaire, Decision Balance, and Self-Efficacy. The study measures will be completed at baseline, post intervention, and 1 month and 3 months after the intervention.Discussion: The results of this intervention could be used as adjunct therapy for adolescents with IGD.Trial Registration: Clinical Trial Registration Center of Iran (IRCT) IRCT20181226042140N1 . Registered on June 9, 2020. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults who had childhood cancer are at increased risk for insomnia, due to being critically ill during an important phase of their life for the development of good sleep habits. Insomnia is disabling and prevalent after childhood cancer (26-29%) and negatively impacts quality of life, fatigue, pain, and general functioning and is often associated with other (mental) health problems. Insomnia and a history of childhood cancer both increase the risk of adverse health outcomes, posing a double burden for adolescents who had childhood cancer. The first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I). However, access to this type of care is often limited. The guided online CBT-I treatment "i-Sleep" has been developed to facilitate access via online care. i-Sleep is shown effective in adult (breast cancer) patients, but it is unknown if iCBT-I is effective in pediatric oncology.Methods/design: We developed a youth version of i-Sleep. Our aim is to evaluate its effectiveness in a national randomized-controlled clinical trial comparing iCBT-I to a waiting-list control condition at 3 and 6 months (n = 70). The intervention group will be also assessed at 12 months to see whether the post-test effects are maintained. Adolescents and young adults aged 12-30 years with insomnia, diagnosed with (childhood) cancer, currently at least 6 months since their last cancer treatment will be eligible. Outcomes include sleep efficiency (actigraphic), insomnia severity (self-report), sleep and circadian activity rhythm parameters, fatigue, health-related quality of life, perceived cognitive functioning, chronic distress, depressive and anxiety symptoms, and intervention acceptability.Discussion: Insomnia is prevalent in the pediatric oncology population posing a double health burden for adolescents and young adults who had childhood cancer. If guided iCBT-I is effective, guidelines for insomnia can be installed to treat insomnia and potentially improve quality of life and the health of adolescents and young adults who had childhood cancer.Trial Registration: NL7220 (NTR7419; Netherlands Trial register). Registered on 2 August 2018. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder is among the most burdening and costly chronic health hazards. Since its prognosis is poor and treatment effectiveness is moderate at best, prevention would be the strategy of first choice. Insomnia may be the best modifiable risk factor. Insomnia is highly prevalent (4–10%) and meta-analysis estimates ±13% of people with insomnia to develop depression within a year. Among people with insomnia, recent work identified three subtypes with a particularly high lifetime risk of depression. The current randomized controlled trial (RCT) evaluates the effects of internet-guided Cognitive Behavioral Therapy for Insomnia (CBT-I), Chronobiological Therapy (CT), and their combination on insomnia and the development of depressive symptoms. Methods: We aim to include 120 participants with Insomnia Disorder (ID) of one of the three subtypes that are more prone to develop depression. In a two by two factorial repeated measures design, participants will be randomized to CBT-I, CT, CBT-I + CT or treatment as usual, and followed up for one year. The primary outcome is the change, relative to baseline, of the severity of depressive symptoms integrated over four follow-ups spanning one year. Secondary outcome measures include a diagnosis of major depressive disorder, insomnia severity, sleep diaries, actigraphy, cost-effectiveness, and brain structure and function. Discussion: Pre-selection of three high-risk insomnia subtypes allows for a sensitive assessment of the possibility to prevent the development and worsening of depressive symptoms through interventions targeting insomnia. Trial registration: Netherlands Trial Register (NL7359). Registered on 19 October 2018. [ABSTRACT FROM AUTHOR]

Background: Cancer related fatigue (CRF) is one of the most prevalent and distressing long-term complaints reported by (non-) Hodgkin survivors. To date there has been no standard treatment for CRF in this population. A novel and promising approach to treat CRF is exposure to bright white light therapy. Yet, large scale randomized controlled trials testing its efficacy in these patients and research on potential mechanisms is lacking. The objective of the current study is to investigate the efficacy of light therapy as a treatment for CRF and to explore potential mechanisms.Methods/design: In a multicenter, randomized controlled trial we are evaluating the efficacy of two intensities of light therapy in reducing CRF complaints and restrictions caused by CRF in survivors of Hodgkin lymphoma or diffuse large B-cell lymphoma. Secondary outcomes include sleep quality, depression, anxiety, quality of life, cognitive complaints, cancer worries, fatigue catastrophizing, self-efficacy to handle fatigue, biological circadian rhythms of melatonin, cortisol and activity, and biomarkers of inflammation. We will recruit 128 survivors, with fatigue complaints, from academic and general hospitals. Survivors are randomized to either an intervention (exposure to bright white light) or a comparison group (exposure to dim white light). The longitudinal design includes four measurement points at baseline (T0), post-intervention at 3.5 weeks (T1), 3 months post-intervention (T2) and 9 months post-intervention (T3). Each measurement point includes self-reported questionnaires and actigraphy (10 days). T0 and T1 measurements also include collection of blood and saliva samples.Discussion: Light therapy has the potential to be an effective treatment for CRF in cancer survivors. This study will provide insights on its efficacy and potential mechanisms. If proven to be effective, light therapy will provide an easy to deliver, low-cost and low-burden intervention, introducing a new era in the treatment of CRF.Trial Registration: The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ). [ABSTRACT FROM AUTHOR]

Background: Perimenopausal insomnia is one of the core symptoms of the menopausal transition. Acupuncture is considered to exert a positive effect on restoring the normal sleep-wake cycle. However, there is little intuitive evidence besides evaluation using clinical effectiveness scales. We therefore designed this study, aiming to use more intuitive and reliable detection techniques such as functional magnetic resonance imaging before and after applying acupuncture to provide neuroimaging evidence, as well as to verify the effectiveness with other curative effect indicators.Methods/design: This study is a randomized, assessor-statistician-blinded, positive medicine controlled trial involving 40 participants. A total of 40 eligible patients with perimenopausal insomnia will be randomly assigned to two groups in a 1:1 ratio as an intervention group using acupuncture and a control group taking estazolam. Participants in the intervention group will receive six acupuncture treatment sessions per week for 4 consecutive weeks, for a total of 24 sessions during the study. Meanwhile, the medicine control group will be prescribed estazolam 1-2 mg/day to be taken 30 minutes before sleep for 4 weeks. The primary outcome is the Pittsburgh Sleep Quality Index. Secondary outcomes are the micro-movement sensitive mattress-type sleep monitoring system, the Hamilton Depression Scale, and the Hamilton Anxiety Scale. All outcomes will be evaluated before and after treatment. The safety of interventions will be assessed at every visit.Discussion: The results of this trial, which will be available in 2018, will investigate the impact of acupuncture treating perimenopausal insomnia from assessment of the sleep architecture, hormone level, and emotional-circuit neurological function, and will uncover the effective mechanism of acupuncture regulating the emotional center integrated effect.Trial Registration: Chinese Clinical Trials Register, ChCTR-IPC-16007832 . Registered on 26 January 2016. [ABSTRACT FROM AUTHOR]

Background: A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients. Methods/design: In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis. Discussion: Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected therapeutic effect, and expectancies are rated prior to the start of treatment. Ideally, the design of a future study on BLT should include two extra treatment arms where BLT and control light are administered at random times. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder affecting 5 % of children worldwide. A prevalent problem for children with ADHD is initial insomnia. The gold standard treatment to manage ADHD symptoms is stimulant medications, which may exacerbate the severity of existing initial insomnia. Currently, no gold standard treatment option exists for initial insomnia for these children. Melatonin, a hormone and a popular natural health product, is commonly provided to children by parents and recommended by healthcare providers, but high quality pediatric evidence is lacking.Methods/design: This trial is a multicenter randomized triple-blind, placebo-controlled, parallel-group, randomized, controlled trial (RCT), in which each participant is offered an N-of-1 trial. An N-of-1 trial is a multiple-crossover, randomized, controlled trial conducted in a single individual. For the N-of-1 trial, each participant will undergo three pairs of treatment/placebo periods; each period is 1 week in length. Half the participants will have melatonin in the first period, the other half will start with placebo, and this will make up the parallel-group RCT. The primary outcome will be mean difference in sleep onset latency as measured by sleep diaries. A comparison of treatment effects yielded by the RCT data versus the aggregated N-of-1 trial data will also be assessed.Discussion: This trial will provide rigorous evidence for the effectiveness of melatonin in children with ADHD on stimulants who experience initial insomnia. Further, this study will provide the first prospectively planned head-to-head comparison of RCT data with pooled data from a series of N-of-1 trials. Aggregated N-of-1 trials may be a powerful tool to produce high quality clinical trial evidence.Trial Registration Numbers: ClinicalTrials.gov, NCT02333149 . Registered on 16 December 2014. Australian New Zealand Clinical Trials Registry, ACTRN12614000542695 . Registered on 21 May 2014. [ABSTRACT FROM AUTHOR]

Background: Chronic low back pain is the most frequent pain condition in Veterans and causes substantial suffering, decreased functional capacity, and lower quality of life. Symptoms of post-traumatic stress, depression, and mild traumatic brain injury are highly prevalent in Veterans with back pain. Yoga for low back pain has been demonstrated to be effective for civilians in randomized controlled trials. However, it is unknown if results from previously published trials generalize to military populations.Methods/design: This study is a parallel randomized controlled trial comparing yoga to education for 120 Veterans with chronic low back pain. Participants are Veterans ≥18 years old with low back pain present on at least half the days in the past six months and a self-reported average pain intensity in the previous week of ≥4 on a 0-10 scale. The 24-week study has an initial 12-week intervention period, where participants are randomized equally into (1) a standardized weekly group yoga class with home practice or (2) education delivered with a self-care book. Primary outcome measures are change at 12 weeks in low back pain intensity measured by the Defense and Veterans Pain Rating Scale (0-10) and back-related function using the 23-point Roland Morris Disability Questionnaire. In the subsequent 12-week follow-up period, yoga participants are encouraged to continue home yoga practice and education participants continue following recommendations from the book. Qualitative interviews with Veterans in the yoga group and their partners explore the impact of chronic low back pain and yoga on family relationships. We also assess cost-effectiveness from three perspectives: the Veteran, the Veterans Health Administration, and society using electronic medical records, self-reported cost data, and study records.Discussion: This study will help determine if yoga can become an effective treatment for Veterans with chronic low back pain and psychological comorbidities.Trial Registration: ClinicalTrials.gov: NCT02224183. [ABSTRACT FROM AUTHOR]

Background: By the age of sixteen, one in five children will sustain a mild traumatic brain injury also known as concussion. Our research found that one in seven school children with mild traumatic brain injury suffer post-concussion syndrome symptoms for three months or longer. Post-concussion syndrome is associated with significant disability in the child and his/her family and yet there are no evidence-based medical treatments available. Melatonin has several potential mechanisms of action that could be useful following mild traumatic brain injury, including neuroprotective effects. The aim of this study is to determine if treatment with melatonin improves post-concussion syndrome in youths following mild traumatic brain injury. Our hypothesis is that treatment of post-concussion syndrome following mild traumatic brain injury with 3 or 10 mg of sublingual melatonin for 28 days will result in a decrease in post-concussion syndrome symptoms compared with placebo. Methods/Design: Ninety-nine youths with mild traumatic brain injury, aged between 13 and 18 years, who are symptomatic at 30 days post-injury will be recruited. This study will be conducted as a randomized, double blind, placebo-controlled superiority trial of melatonin. Three parallel treatment groups will be examined with a 1:1:1 allocation: sublingual melatonin 3 mg, sublingual melatonin 10 mg, and sublingual placebo. Participants will receive treatment for 28 days. The primary outcome is a change on the Post-Concussion Symptom Inventory (Parent and Youth). The secondary outcomes will include neurobehavioral function, health-related quality of life and sleep. Neurophysiological and structural markers of change, using magnetic resonance imaging techniques and transcranial magnetic stimulation, will also be investigated. Discussion: Melatonin is a safe and well-tolerated agent that has many biological properties that may be useful following a traumatic brain injury. This study will determine whether it is a useful treatment for children with post-concussion syndrome. Recruitment commenced on 4 December 2014. [ABSTRACT FROM AUTHOR]

Background: Chinese herbal medicine is one of the most popular Chinese medicine (CM) therapies for primary insomnia. One of the important characteristics of CM is that different Chinese clinicians give different prescriptions even for the same patient. However, there must be some fixed drug patterns in every clinician's prescriptions. This study aims to screen the effective core drug patterns in primary insomnia treatment of three prestigious Chinese clinicians. Methods/design: A triple-blind, randomized, placebo-controlled, parallel-group clinical trial will be performed. Three clinicians will diagnose and treat every eligible patient individually and independently, producing three prescriptions from three clinicians for every patient. Patients will equally be randomized to one of four groups - medical group A, medical group B, medical group C, or placebo group - and observed for efficacy of treatment. The sample will include primary insomnia patients meeting DSM IV-TR criteria, Spiegel scale score >18, and age 18 to 65 years. A sequential design is employed. Interim analysis will be conducted when between 80 and 160 patients complete the study. The interim study could be stopped and treated as final if a statistically significant difference between treatment and placebo groups can be obtained and core effective drug patterns can be determined. Otherwise, the study continues until the maximum sample size reaches 300. Treatment of the CM group is one of three Chinese clinicians' prescriptions, who provide independently prescriptions based on their own CM theory and the patient's disease condition. Assessment will be by sleep diary and Pittsburgh sleep quality index, and CM symptoms and signs will be measured. Primary outcome is total sleep time. Assessment will be carried out at the washout period, weeks 1, 2, 3, and 4 and 4th week after the end of treatment. Effectiveness analysis will be per intent to treat. A multi-dimension association rule and scale-free networks method will be used to explore the effective core drug patterns. Discussion: The effective core drug patterns will be found through analyzing several prestigious CM clinicians' treatment information. Screening the effective core drug patterns from prestigious clinicians can accelerate the development of new CM drugs. [ABSTRACT FROM AUTHOR]

Background: Sleep deficiency affects a majority of pregnant women with significant impact on daily function, mood, and pregnancy and birth outcomes. This ongoing study combines two evidence-based strategies for improving sleep and mood, mindfulness meditation and cognitive-behavioral therapy for insomnia (CBT-I), in a unique online format to address the particular needs of pregnant women. The purpose of this study is to test the feasibility and estimate the efficacy of this novel 6-week online mindfulness meditation intervention to help pregnant women in remission from depression self-manage insomnia. Methods: This is a two-arm, parallel group randomized controlled trial. A total of 50 pregnant women between 12 and 28 weeks gestation will be recruited from the community and randomly assigned to a mindfulness or education-only control group in a 1:1 ratio. During the study, all participants will complete six weekly online modules, daily sleep diaries, and optional participation in a treatment-specific online discussion forum. Feasibility outcome measures will include study recruitment, retention, intervention adherence (number of online modules completed, number of meditation days per week), and intervention acceptability (8-item questionnaire). The primary clinical outcome measure will be sleep quality measured with the Pittsburgh Sleep Quality Index. Secondary outcome measures will include sleep measured with actigraphy and diaries (sleep efficiency, total sleep time, total wake time), Patient-Reported Outcomes Measurement Information System (PROMIS) measures (fatigue, sleep-related impairment, sleep disturbance); mood (depression, anxiety, positive affect, quality of life); and self-management and behavior change (potential self-efficacy, self-regulation, sleep problem acceptance, and trait mindfulness). Assessments will occur at baseline and post-intervention; an additional acceptability survey will be completed 4 weeks postpartum. Analyses will examine within-group differences in outcome change scores from baseline to post-intervention. Open-ended feedback will be analyzed using qualitative content analysis. Discussion: This research is innovative in addressing sleep in pregnancy using a self-management research design and methods that can be accessible and cost-effective for large numbers of pregnant women. The results from this study will inform intervention refinement and efficacy testing of the intervention in a larger randomized controlled trial. Trial registration: ClinicalTrials.gov, NCT04016428. Registered on 11 July 2019. Updated version registered on 26 July 2019. [ABSTRACT FROM AUTHOR]

Background: Unipolar depression is one of the most important mental disorders. Insomnia is a symptom of cardinal importance in depression. It increases the risk to develop depression, negatively affects disease trajectory, is the most common symptom after remission, increases the risk of relapse, and is associated with higher suicide rates. Existing therapies for insomnia in depression have limitations. Further adjuvant therapies are therefore needed. Acute aerobic exercise has been shown to have beneficial effects on sleep in healthy individuals and patients with insomnia. We therefore hypothesize that a single session of aerobic exercise has a positive impact on sleep in patients with unipolar depression. This trial aims to investigate the effects of a single bout of aerobic exercise on the subsequent night's sleep in patients with depression.Methods/design: This is a two-arm parallel group, randomized, outcome assessor blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression (without a psychotic episode) are included. Exclusion criteria are regular use of hypnotic agents, opioids, and certain beta-blockers, as well as the presence of factors precluding exercise, history of epilepsy, restless legs syndrome, moderate obstructive sleep apnea, and a BMI > 40. The intervention is a single bout of aerobic exercise, performed for 30 min on a bicycle ergometer at 80% individual anaerobic threshold. The control group sits and reads for 30 min. The primary outcome is sleep efficiency measured by polysomnography. Secondary outcomes include further polysomnographic variables, subjective pre-sleep arousal, nocturnal cardiovascular autonomic modulation, subjective sleep quality, daytime sleepiness, and adverse events. According to the sample size calculation, a total of 92 patients will be randomized using minimization.Discussion: This trial will add new information to the body of knowledge concerning the treatment of insomnia in patients with depression. Thereby, the results will inform decision makers on the utility of acute aerobic exercise.Trial Registration: Clinicaltrials.gov, NCT03673397 . Protocol version 1 registered on 17 September 2018. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (KOA) is commonly seen and has a high occurrence in the middle-aged and elderly. It is characterized by the degeneration and secondary bone hyperplasia of the articular cartilage; the pathologic changes are irreversible. Therefore, treatment of KOA is mainly focused on relieving pain, reducing inflammation, improving or restoring joint function, delaying disease progression, and increasing quality of life. Crossbow needle therapy of the Miao ethnic minority group is intended for KOA treatment and has been widely used. Studies of small sample size have seen significant improvement on pain relief, stiffness, and joint function.Methods/design: The trial is a randomized, multicenter, parallel, non-inferiority study. Three hundred and six patients will be randomly assigned to a crossbow needle group (n = 153) and an acupuncture group (n = 153). Patients in each group will receive treatment every other day, three times a week, 20 times in total. Follow-up will be conducted 15 days and 30 days after treatment. The primary outcome will be the Western Ontario and McMaster Osteoarthritis Index (WOMAC) score at baseline, the end of treatment, first follow-up, and second follow-up. The secondary outcomes will include Lysholm knee score, Japanese Orthopedic Association (JOA) knee score, visual analogue scale (VAS), and the MOS 36-item short-form health survey (SF-36).Discussion: The results of the trial will compare the efficacy on KOA between crossbow needle group and acupuncture group and will be expected to make a systematic and objective evaluation of crossbow needle therapy.Trial Registration: ChiCTR, ChiCTR-INR-16008032 . Registered on 12 March 2016. [ABSTRACT FROM AUTHOR]

Background: Most people suffering chronic pain are plagued by sleeping difficulties. Cognitive behaviour therapy has produced promising results for insomnia comorbid with chronic pain, but the access to such treatment is often limited. Over the last ten years, interventions aiming to increase cognitive flexibility and physical activity have been assumed to be effective treatments for a variety of conditions, including insomnia and chronic pain. If proven effective, these treatments could constitute the first steps in a stepped care model for chronic pain and insomnia.Methods: Two hundred ninety-nine chronic pain subjects were randomized to Exercise, ACT-based stress management (ACT-bsm), or an active control group. Two hundred thirty-two participants (78%) received their allocated intervention at least to some extent. These participants were evaluated using mixed model analyses for changes in sleep (Insomnia Severity Index, ISI), pain intensity, depression, and anxiety immediately after treatment, six months and twelve months after treatment.Results: The mixed model analyses revealed that Exercise had a positive effect on insomnia compared with the control group and the effect remained after 12 months. No clear effect (i.e., both for completers and for completers together with treatment non-completers) upon ISI was found for the ACT-bsm. Pain intensity decreased significantly both in the exercise group and in the control group. For the two psychological variables (i.e., symptoms of anxiety and depression) were found significant improvements over time but no group differences. The treatment effects for ISI and pain intensity did not reach clinical significance per definitions presented in other relevant studies.Conclusions: Beneficial significant effects on insomnia was confirmed in the exercise condition. However, these changes were probably not clinically important. For pain intensity a general decrease was found in the Exercise condition and in the control condition, while no change occurred in ACT-bsm. No group differences were found for the two psychological variables.Trial Registration: The study was registered in Clinical Trials (Trial registration: ClinicalTrials.gov Id: NCT02399644 , 21 January 2015, retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Patients on maintenance hemodialysis (MHD) frequently complain of insomnia. Poor sleep quality impairs their quality of life and adversely affects long-term outcome. Previously we applied auricular acupressure therapy (AAT) for MHD patients with insomnia and yielded favorable results. AAT probably improves sleep quality by stimulating the vagus nerve and inhibiting sympathetic overactivity. However, the efficacy of AAT for insomnia in this population is still lacking. The proposed randomized controlled trial (RCT) will evaluate the efficacy and safety of AAT for improvement of sleep quality in MHD patients with insomnia.Methods/design: The proposed study is a multi-center, double-blind (participants and assessors), parallel-group RCT. A total of 112 participants with insomnia will be recruited from six hemodialysis centers in Guangzhou, China, and randomly allocated in a 1:1 ratio to receive auricular acupressure on either active points (AA group) or control points (points irrelevant to insomnia management, SAA group). The treatment will last for 8 weeks prior to a follow-up period of 12 weeks. Evaluation by blinded assessors at baseline, at 8 weeks (end of treatment) as well as at 4-week, 8-week and 12-week follow-ups (after intervention) will include Pittsburgh Sleep Quality Index (PSQI) scores and average weekly dose of hypnotics. The primary endpoint is clinical response rate (percentage of participants who reach a reduction of PSQI global score ≥ 3 in each group) at 8 weeks from baseline. Secondary endpoints include the changes in PSQI scores over time from baseline, as well as the changes in weekly dose of hypnotics.Discussion: This paper describes the rationale and design of a double-blind RCT that aims to determine the efficacy and safety of AAT for insomnia of hemodialysis patients. If successful, this project will provide evidence of the efficacy and safety of AAT for insomnia of hemodialysis patients.Trial Registration: ClinicalTrials.gov , Identifier: NCT03015766 . Registered on 22 December 2016. [ABSTRACT FROM AUTHOR]

Background: To explore if health related quality of life(HRQoL) increased after traditional yoga(TY), mindfulness based cognitive therapy(MBCT), or cognitive behavioral therapy(CBT), in patients on sick leave because of burnout. Methods: Randomized controlled trial, blinded, in ninety-four primary health care patients, block randomized to TY, MBCT or CBT (active control) between September 2007 and November 2009. Patients were living in the Stockholm metropolitan area, Sweden, were aged 18–65 years and were on 50%–100% sick leave. A group treatment for 20 weeks, three hours per week, with homework four hours per week. HRQoL was measured by the SWED-QUAL questionnaire, comprising 67 items grouped into 13 subscales, each with a separate index, and scores from 0 (worse) to 100 (best). SWED-QUAL covers aspects of physical and emotional well-being, cognitive function, sleep, general health and social and sexual functioning. Statistics: Wilcoxon’s rank sum and Wilcoxon’s sign rank tests, Bonett-Price for medians and confidence intervals, and Cohen’s D. Results: Twenty-six patients in the TY (21 women), and 27 patients in both the MBCT (24 women) and in the CBT (25 women), were analyzed. Ten subscales in TY and seven subscales in MBCT and CBT showed improvements, p < 0.05, in several of the main domains affected in burnout, e.g. emotional well-being, physical well-being, cognitive function and sleep. The median improvement ranged from 0 to 27 points in TY, from 4 to 25 points in CBT and from 0 to 25 points in MBCT. The effect size was mainly medium or large. Comparison of treatments showed no statistical differences, but better effect (small) of both TY and MBCT compared to CBT. When comparing the effect of TY and MBCT, both showed a better effect (small) in two subscales each. Conclusions: A 20 week group treatment with TY, CBT or MBCT had equal effects on HRQoL, and particularly on main domains affected in burnout. This indicates that TY, MBCT and CBT can be used as both treatment and prevention, to improve HRQoL in patients on sick leave because of burnout, reducing the risk of future morbidity. Trial registration: July 22, 2012, retrospectively registered. ClinicalTrails.govNCT01168661. Funding: Stockholm County Council, grant 2003–5. [ABSTRACT FROM AUTHOR]