The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial

Study ObjectivesInsomnia increases the risk of negative disease trajectory, relapse, and suicide in patients with depression. We aimed at investigating the effects of a single bout of aerobic exercise, performed after 02:00 pm, on the subsequent night’s sleep in patients with depression.MethodsThe study was designed as 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 were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, and adverse events.ResultsNinety-two patients were randomized to the exercise (N = 46) or control group (N = 46). There were no clinically relevant differences at baseline. Intent-to-treat analysis ANCOVA of follow-up sleep efficiency, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = −0.93, p = 0.59). There was no evidence for significant differences between both groups in any other objective or subjective sleep outcomes, daytime sleepiness, or adverse events. The intervention had an immediate positive effect on mood states, including depressiveness (β = −0.40, p = 0.003).ConclusionsThis is the first trial to study the effects of a single bout of aerobic exercise on sleep in patients with depression to the best of our knowledge. Aerobic exercise had no effect on sleep efficiency but had a strong beneficial effect on mood and did not increase adverse outcomes. These results add to the growing body of evidence that, contrary to sleep hygiene recommendations, exercise after 02:00 pm is not detrimental for sleep.Clinical Trial RegistrationClinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03673397. Protocol registered on September 17, 2018.     

Evening binge alcohol disrupts cardiovagal tone and baroreflex function during polysomnographic sleep

Study ObjectivesBinge alcohol consumption is associated with increased cardiovascular risk. The effects of evening binge alcohol consumption (i.e. 4–5 beverages within 2 h) on the vagal components of HRV and cardiovagal baroreflex sensitivity (cvBRS) during sleep remain largely equivocal. The present study examined the effects of evening binge alcohol consumption on nocturnal cardiac vagal tone and baroreflex sensitivity during stage N2, slow wave (SWS), and rapid eye movement (REM) sleep. We hypothesized that evening binge drinking would reduce HRV and cvBRS in each sleep stage.MethodsFollowing a familiarization night within the laboratory, twenty-three participants were examined following a night of binge alcohol consumption and a fluid control (randomized, crossover design). A quality nocturnal beat-to-beat blood pressure signal was obtained in both conditions in 16 participants (seven men, nine women; 25 ± 1 years).ResultsBinge drinking reduced both the high frequency (HF) and time-domain components (i.e. pNN50 and RMSSD) of HRV in stage N2 sleep, SWS, and REM. In addition, cvBRS up-up (vagal activation) was reduced following binge alcohol consumption in stage N2 (21 ± 3 vs. 15 ± 3 ms/mmHg, p = 0.035) and REM (15[11–28] vs. 11[9–18] ms/mmHg, p = 0.009). Binge alcohol consumption reduced cvBRS down-down (vagal withdrawal) in stage N2 (23 ± 2 vs. 14 ± 2 ms/mmHg, p < 0.001), SWS (20[14–30] vs. 14[9–17] ms/mmHg, p = 0.022), and REM (14[11–24] vs. 10[7–15] ms/mmHg, p = 0.006).ConclusionsEvening binge alcohol consumption disrupts cardiac vagal tone and baroreflex function during nearly all sleep stages. These findings provide mechanistic insight into the potential role of binge drinking and alcohol abuse on cardiovascular risk.Clinical Trials DetailsAlcohol and Neural Cardiovascular Control in Binge Drinkers, www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03567434","term_id":"NCT03567434"}}NCT03567434, {"type":"clinical-trial","attrs":{"text":"NCT03567434","term_id":"NCT03567434"}}NCT03567434.     

The effect of sleep–wake intraindividual variability in digital cognitive behavioral therapy for insomnia: a mediation analysis of a large-scale RCT

Study ObjectivesDigital cognitive behavioral therapy for insomnia (dCBT-I) is an effective treatment for insomnia. However, less is known about mediators of its benefits. The aim of the present study was to test if intraindividual variability in sleep (IIV) was reduced with dCBT-I, and whether any identified reduction was a mediator of dCBT-I on insomnia severity and psychological distress.MethodsIn a two-arm randomized controlled trial (RCT), 1720 adults with insomnia (dCBT-I = 867; patient education about sleep = 853) completed the Insomnia Severity Index (ISI), the Hospital Anxiety and Depression Scale (HADS) and sleep diaries, at baseline and 9-week follow-up. Changes in IIV were analyzed using linear mixed modeling followed by mediation analyses of ISI, HADS, and IIV in singular sleep metrics and composite measures (behavioral indices (BI-Z) and sleep disturbance indices (SI-Z)).ResultsdCBT-I was associated with reduced IIV across all singular sleep metrics, with the largest between-group effect sizes observed for sleep onset latency (SOL). Reduced IIV for SOL and wake after sleep onset had the overall greatest singular mediating effect. For composite measures, SI-Z mediated change in ISI (b = −0.74; 95% confidence interval (CI) −1.04 to −0.52; 13.3%) and HADS (b = −0.40; 95% CI −0.73 to −0.18; 29.2%), while BI-Z mediated minor changes.ConclusionReductions in IIV in key sleep metrics mediate significant changes in insomnia severity and especially psychological distress when using dCBT-I. These findings offer important evidence regarding the therapeutic action of dCBT-I and may guide the future development of this intervention.Clinical trials Name: Overcoming Insomnia: Impact on Sleep, Health and Work of Online CBT-I Registration number: NCT02558647 URL: https://clinicaltrials.gov/ct2/show/NCT02558647?cond=NCT02558647&draw=2&rank=1     

Electroencephalographic sleep macrostructure and sleep spindles in early infancy

Study ObjectivesSleep features in infancy are potential biomarkers for brain maturation but poorly characterized. We describe normative values for sleep macrostructure and sleep spindles at 4–5 months of age.MethodsHealthy term infants were recruited at birth and had daytime sleep electroencephalograms (EEGs) at 4–5 months. Sleep staging was performed and five features were analyzed. Sleep spindles were annotated and seven quantitative features were extracted. Features were analyzed across sex, recording time (am/pm), infant age, and from first to second sleep cycles.ResultsWe analyzed sleep recordings from 91 infants, 41% females. Median (interquartile range [IQR]) macrostructure results: sleep duration 49.0 (37.8–72.0) min (n = 77); first sleep cycle duration 42.8 (37.0–51.4) min; rapid eye movement (REM) percentage 17.4 (9.5–27.7)% (n = 68); latency to REM 36.0 (30.5–41.1) min (n = 66). First cycle median (IQR) values for spindle features: number 241.0 (193.0–286.5), density 6.6 (5.7–8.0) spindles/min (n = 77); mean frequency 13.0 (12.8–13.3) Hz, mean duration 2.9 (2.6–3.6) s, spectral power 7.8 (4.7–11.4) µV², brain symmetry index 0.20 (0.16–0.29), synchrony 59.5 (53.2–63.8)% (n = 91). In males, spindle spectral power (µV²) was 24.5% lower (p = .032) and brain symmetry index 24.2% higher than females (p = .011) when controlling for gestational and postnatal age and timing of the nap. We found no other significant associations between studied sleep features and sex, recording time (am/pm), or age. Spectral power decreased (p < .001) on the second cycle.ConclusionThis normative data may be useful for comparison with future studies of sleep dysfunction and atypical neurodevelopment in infancy. Clinical Trial Registration: BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT) (BabySMART)URL: https://clinicaltrials.gov/ct2/show/results/NCT03381027?view=results.ClinicalTrials.gov Identifier: NCT03381027     

Efficacy of a stepped care approach to deliver cognitive-behavioral therapy for insomnia in cancer patients: a noninferiority randomized controlled trial

Study ObjectivesCognitive-behavioral therapy for insomnia (CBT-I) is the recommended first-line treatment for cancer-related insomnia, but its accessibility is very limited in routine care. A stepped care approach has been recommended as a cost-effective way to make CBT-I more widely accessible. However, no controlled study has yet been published about the efficacy of this approach. The goal of this noninferiority randomized controlled trial (RCT) was to compare the short and long-term efficacy of a stepped care CBT-I (StepCBT-I) to a standard face-to-face CBT-I (StanCBT-I).MethodsA total of 177 cancer patients were randomized to: (1) StanCBT-I (6 face-to-face CBT-I sessions; n = 59) or (2) StepCBT-I (n = 118). In the StepCBT-I group, patients with less severe insomnia first received a web-based CBT-I (n = 65), while those with more severe insomnia received 6 face-to-face CBT-I sessions (n = 53). In both cases, patients could receive up to three booster sessions of CBT-I if they still had insomnia symptoms following this first step.ResultsResults indicated that the Step-CBT-I group showed an Insomnia Severity Index score reduction and a sleep efficiency (on a sleep diary) increase that was not significantly inferior to that of StanCBT-I at all post-treatment time points. Analyses of secondary outcomes indicated significant time effects (ps < .001) and no significant group-by-time interactions (ps from .07 to .91) on other sleep diary parameters, sleep medication use, depression, anxiety, fatigue, and quality of life scores.Conclusion(s)The efficacy of stepped care CBT-I is not inferior to that of a standard face-to-face intervention and is a valuable approach to making this treatment more widely accessible to cancer patients.Trial registrationClinicalTrials.gov Identifier: NCT01864720 (https://clinicaltrials.gov/ct2/show/NCT01864720?term=Savard&draw=2&rank=6; Stepped Care Model for the Wider Dissemination of Cognitive-Behavioural Therapy for Insomnia Among Cancer Patients).     

Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: a CENC study

Study ObjectivesSleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI.MethodsIn an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury.ResultsIn the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, $\bar{x}$ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency ($\bar{x}$ = 18.0 vs 21.0, p = 0.0005, d = –0.65) and stop-go tests ($\bar{x}$ = 30.1 vs 31.1, p = 0.024, d = –0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (beta = 0.22, p = 0.00002) and tau (beta = 0.14, p = 0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores ($\bar{x}$ = 3.8 vs 2.7, p = 0.0005), raising the possibility that the PSQI might be partly secondary to OSA.ConclusionsPoor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.     

Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label,Multi-Center,Non-Interventional Study

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: {"type":"clinical-trial","attrs":{"text":"NCT 01273454","term_id":"NCT01273454"}}NCT 01273454).     

A Mobile App to Stabilize Daily Functional Activity of Breast Cancer Patients in Collaboration With the Physician: A Randomized Controlled Clinical Trial

BackgroundThe well-being of breast cancer patients and reporting of adverse events require close monitoring. Mobile apps allow continuous recording of disease- and medication-related symptoms in patients undergoing chemotherapy.ObjectiveThe aim of the study was to evaluate the effects of a mobile app on patient-reported daily functional activity in a supervised and unsupervised setting.MethodsWe conducted a randomized controlled study of 139 breast cancer patients undergoing chemotherapy. Patient status was self-measured using Eastern Cooperative Oncology Group scoring and Common Terminology Criteria for Adverse Events. Participants were randomly assigned to a control group, an unsupervised group that used a mobile app to record data, or a supervised group that used the app and reviewed data with a physician. Primary outcome variables were change in daily functional activity and symptoms over three outpatient visits.ResultsFunctional activity scores declined in all groups from the first to second visit. However, from the second to third visit, only the supervised group improved, whereas the others continued to decline. Overall, the supervised group showed no significant difference from the first (median 90.85, IQR 30.67) to third visit (median 84.76, IQR 18.29, P=.72). Both app-using groups reported more distinct adverse events in the app than in the questionnaire (supervised: n=1033 vs n=656; unsupervised: n=852 vs n=823), although the unsupervised group reported more symptoms overall (n=4808) in the app than the supervised group (n=4463).ConclusionsThe mobile app was associated with stabilized daily functional activity when used under collaborative review. App-using participants could more frequently report adverse events, and those under supervision made fewer and more precise entries than unsupervised participants. Our findings suggest that patient well-being and awareness of chemotherapy adverse effects can be improved by using a mobile app in collaboration with the treating physician.ClinicalTrialClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02004496","term_id":"NCT02004496"}}NCT02004496; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02004496","term_id":"NCT02004496"}}NCT02004496 (Archived by WebCite at http://www.webcitation.org/6k68FZHo2)     

It's LiFe! Mobile and Web-Based Monitoring and Feedback Tool Embedded in Primary Care Increases Physical Activity: A Cluster Randomized Controlled Trial

BackgroundPhysical inactivity is a major public health problem. The It’s LiFe! monitoring and feedback tool embedded in the Self-Management Support Program (SSP) is an attempt to stimulate physical activity in people with chronic obstructive pulmonary disease or type 2 diabetes treated in primary care.ObjectiveOur aim was to evaluate whether the SSP combined with the use of the monitoring and feedback tool leads to more physical activity compared to usual care and to evaluate the additional effect of using this tool on top of the SSP.MethodsThis was a three-armed cluster randomised controlled trial. Twenty four family practices were randomly assigned to one of three groups in which participants received the tool + SSP (group 1), the SSP (group 2), or care as usual (group 3). The primary outcome measure was minutes of physical activity per day. The secondary outcomes were general and exercise self-efficacy and quality of life. Outcomes were measured at baseline after the intervention (4-6 months), and 3 months thereafter.ResultsThe group that received the entire intervention (tool + SSP) showed more physical activity directly after the intervention than Group 3 (mean difference 11.73, 95% CI 6.21-17.25; P<.001), and Group 2 (mean difference 7.86, 95% CI 2.18-13.54; P=.003). Three months after the intervention, this effect was still present and significant (compared to Group 3: mean difference 10.59, 95% CI 4.94-16.25; P<.001; compared to Group 2: mean difference 9.41, 95% CI 3.70-15.11; P<.001). There was no significant difference in effect between Groups 2 and 3 on both time points. There was no interaction effect for disease type.ConclusionsThe combination of counseling with the tool proved an effective way to stimulate physical activity. Counseling without the tool was not effective. Future research about the cost-effectiveness and application under more tailored conditions and in other target groups is recommended.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01867970","term_id":"NCT01867970"}}NCT01867970, https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01867970","term_id":"NCT01867970"}}NCT01867970 (archived by WebCite at http://www.webcitation.org/6a2qR5BSr).     

Surviving and Thriving With Cancer Using a Web-Based Health Behavior Change Intervention: Randomized Controlled Trial

Background

Given the substantial improvements in cancer screening and cancer treatment in the United States, millions of adult cancer survivors live for years following their initial cancer diagnosis and treatment. However, latent side effects can occur and some symptoms can be alleviated or managed effectively via changes in lifestyle behaviors.

Objective

The purpose of this study was to test the effectiveness of a six-week Web-based multiple health behavior change program for adult survivors.

Methods

Participants (n=352) were recruited from oncology clinics, a tumor registry, as well as through online mechanisms, such as Facebook and the Association of Cancer Online Resources (ACOR). Cancer survivors were eligible if they had completed their primary cancer treatment from 4 weeks to 5 years before enrollment. Participants were randomly assigned to the Web-based program or a delayed-treatment control condition.

Results

In total, 303 survivors completed the follow-up survey (six months after completion of the baseline survey) and participants in the Web-based intervention condition had significantly greater reductions in insomnia and greater increases in minutes per week of vigorous exercise and stretching compared to controls. There were no significant changes in fruit and vegetable consumption or other outcomes.

Conclusions

The Web-based intervention impacted insomnia and exercise; however, a majority of the sample met or exceeded national recommendations for health behaviors and were not suffering from depression or fatigue at baseline. Thus, the survivors were very healthy and well-adjusted upon entry and their ability to make substantial health behavior changes may have been limited. Future work is discussed, with emphasis placed on ways in which Web-based interventions can be more specifically analyzed for benefit, such as in regard to social networking.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00962494","term_id":"NCT00962494"}}NCT00962494; http://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00962494","term_id":"NCT00962494"}}NCT00962494 (Archived by WebCite at http://www.webcitation.org/6NIv8Dc6Q).     

Effects of nocturnal wearing of dentures on the quality of sleep and oral-health-related quality in edentate elders with untreated sleep apnea: a randomized cross-over trial

Study ObjectivesThis study aims to assess whether the nocturnal wear of dentures has an effect on the quality of sleep and oral-health-related quality of life of the edentulous elderly with untreated sleep apnea.MethodsA single-blind randomized cross-over design with two sequences and two periods was used. Participants (n = 77) were randomly assigned either to sequence 1 (nocturnal wear followed by nocturnal nonwear of the denture for 30–30 days) or sequence 2 (nocturnal nonwear followed by nocturnal wear of denture for 30–30 days). The primary sleep outcome was the quality of sleep, assessed through sleep fragmentation measured as Apnea–Hypopnea Index (AHI) and respiratory arousal from portable polysomnography. Secondary outcomes were daytime sleepiness, sleep quality (Pittsburgh Sleep Quality Index, PSQI) and oral-health-related quality of life measured by validated questionnaires.ResultsThe mean paired difference in AHI scores for the period of wearing versus not wearing dentures at night was small 1.0 event per hour (p = 0.50; 95% confidence interval (CI) = −2.0 to 4.1). The mean respiratory arousal index was higher when wearing dentures at night than when not wearing dentures at night, with a mean paired difference of 2.3 events per hour (p = 0.05; 95% CI = 0.0 to 4.6). No difference in sleepiness and PSQI were noted. Wearing dentures at night resulted in a statistically significantly higher mean score of psychological discomfort when compared to not wearing dentures at night.ConclusionsThe results provide some support to usual practice guidelines to remove dentures at night in edentulous elders suffering from sleep apnea.Clinical trial registrationNCT01868295.     

A 12-Week,Randomized, Double-Blind,Placebo-Controlled Study Evaluating the Effect of Eszopiclone 2 mg on Sleep/Wake Function in Older Adults with Primary and Comorbid Insomnia

Background:

Longer-term pharmacologic studies for insomnia in older individuals are sparse.

Objective:

To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia.

Methods:

Participants (65–85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) ≤ 6 h, and wake time after sleep onset (WASO) ≥ 45 min. Participants were randomized to 12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, well-being, ability to function) were assessed. AEs were monitored.

Results:

Subjects treated with 2 mg eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for eszopiclone (P-values ≤ 0.01), indicating no rebound. The most common AEs (≥ 5%) were headache (eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%).

Conclusion:

In this Phase IV trial of older adults with insomnia, eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated.

Clinical Trial Information:

A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #{"type":"clinical-trial","attrs":{"text":"NCT00386334","term_id":"NCT00386334"}}NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00386334","term_id":"NCT00386334"}}NCT00386334?term=eszopiclone&rank=24

Citation:

Ancoli-Israel S; Krystal AD; McCall WV; Schaefer K; Wilson A; Claus R; Rubens R; Roth T. A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia. SLEEP 2010;33(2):225-234.     

Diabetes Prevention and Weight Loss with a Fully Automated Behavioral Intervention by Email,Web, and Mobile Phone: A Randomized Controlled Trial Among Persons with Prediabetes

BackgroundOne-third of US adults, 86 million people, have prediabetes. Two-thirds of adults are overweight or obese and at risk for diabetes. Effective and affordable interventions are needed that can reach these 86 million, and others at high risk, to reduce their progression to diagnosed diabetes.ObjectiveThe aim was to evaluate the effectiveness of a fully automated algorithm-driven behavioral intervention for diabetes prevention, Alive-PD, delivered via the Web, Internet, mobile phone, and automated phone calls.MethodsAlive-PD provided tailored behavioral support for improvements in physical activity, eating habits, and factors such as weight loss, stress, and sleep. Weekly emails suggested small-step goals and linked to an individual Web page with tools for tracking, coaching, social support through virtual teams, competition, and health information. A mobile phone app and automated phone calls provided further support. The trial randomly assigned 339 persons to the Alive-PD intervention (n=163) or a 6-month wait-list usual-care control group (n=176). Participants were eligible if either fasting glucose or glycated hemoglobin A1c (HbA1c) was in the prediabetic range. Primary outcome measures were changes in fasting glucose and HbA1c at 6 months. Secondary outcome measures included clinic-measured changes in body weight, body mass index (BMI), waist circumference, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio, and Framingham diabetes risk score. Analysis was by intention-to-treat.ResultsParticipants’ mean age was 55 (SD 8.9) years, mean BMI was 31.2 (SD 4.4) kg/m², and 68.7% (233/339) were male. Mean fasting glucose was in the prediabetic range (mean 109.9, SD 8.4 mg/dL), whereas the mean HbA1c was 5.6% (SD 0.3), in the normal range. In intention-to-treat analyses, Alive-PD participants achieved significantly greater reductions than controls in fasting glucose (mean –7.36 mg/dL, 95% CI –7.85 to –6.87 vs mean –2.19, 95% CI –2.64 to –1.73, P<.001), HbA1c (mean –0.26%, 95% CI –0.27 to –0.24 vs mean –0.18%, 95% CI –0.19 to –0.16, P<.001), and body weight (mean –3.26 kg, 95% CI –3.26 to –3.25 vs mean –1.26 kg, 95% CI –1.27 to –1.26, P<.001). Reductions in BMI, waist circumference, and TG/HDL were also significantly greater in Alive-PD participants than in the control group. At 6 months, the Alive-PD group reduced their Framingham 8-year diabetes risk from 16% to 11%, significantly more than the control group (P<.001). Participation and retention was good; intervention participants interacted with the program a median of 17 (IQR 14) of 24 weeks and 71.1% (116/163) were still interacting with the program in month 6.ConclusionsAlive-PD improved glycemic control, body weight, BMI, waist circumference, TG/HDL ratio, and diabetes risk. As a fully automated system, the program has high potential for scalability and could potentially reach many of the 86 million US adults who have prediabetes as well as other at-risk groups.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01479062","term_id":"NCT01479062"}}NCT01479062; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01479062","term_id":"NCT01479062"}}NCT01479062 (Archived by WebCite at http://www.webcitation.org/6bt4V20NR)     

Meta-analysis of age and actigraphy-assessed sleep characteristics across the lifespan

Study ObjectivesSleep quantity and continuity vary across the lifespan. Actigraphy is a reliable and widely used behavioral measure of sleep in research and personal health monitoring. This meta-analysis provides a novel examination of whether age (in years) is associated with actigraphy-assessed sleep across the lifespan.MethodsA systematic search of PubMed, Embase.com, Cochrane CENTRAL, and PsycINFO using “actigraphy” and “sleep” terms provided 7079 titles/abstracts; studies of individuals with known psychiatric or medical comorbidities were excluded. Ninety-one articles (N = 23 365) provided data for six meta-analyses examining sleep duration (k = 89), sleep efficiency (k = 58), bedtime (k = 19) and waketime (k = 9) for individuals ages 6–21, and bedtime (k = 7) and waketime (k = 7) for individuals ages 22 and older.ResultsAt older ages, sleep duration was shorter (r = −0.12) and sleep efficiency was lower (r = −0.05). Older age was associated with later bedtime (r = 0.37) and wake-up time (r = 0.24) from ages 6–21, whereas older age was associated with earlier bedtime (r = −0.66) and wake-up time (r = −0.59) for ages 22 and above. The strength of these associations was modified by study continent, but not by any other moderator.ConclusionsAge was negatively associated with actigraphy-assessed sleep duration and efficiency, but the effects were small in magnitude. On the other hand, large associations were observed between age and sleep timing, despite a smaller literature and the absence of analyzable data for ages 30–60. Changes in sleep timing, rather than changes in sleep duration or continuity, may better characterize the effects of age on human sleep.     

Use of Home Telemonitoring to Support Multidisciplinary Care of Heart Failure Patients in Finland: Randomized Controlled Trial

BackgroundHeart failure (HF) patients suffer from frequent and repeated hospitalizations, causing a substantial economic burden on society. Hospitalizations can be reduced considerably by better compliance with self-care. Home telemonitoring has the potential to boost patients’ compliance with self-care, although the results are still contradictory.ObjectiveA randomized controlled trial was conducted in order to study whether the multidisciplinary care of heart failure patients promoted with telemonitoring leads to decreased HF-related hospitalization.MethodsHF patients were eligible whose left ventricular ejection fraction was lower than 35%, NYHA functional class ≥2, and who needed regular follow-up. Patients in the telemonitoring group (n=47) measured their body weight, blood pressure, and pulse and answered symptom-related questions on a weekly basis, reporting their values to the heart failure nurse using a mobile phone app. The heart failure nurse followed the status of patients weekly and if necessary contacted the patient. The primary outcome was the number of HF-related hospital days. Control patients (n=47) received multidisciplinary treatment according to standard practices. Patients’ clinical status, use of health care resources, adherence, and user experience from the patients’ and the health care professionals’ perspective were studied.ResultsAdherence, calculated as a proportion of weekly submitted self-measurements, was close to 90%. No difference was found in the number of HF-related hospital days (incidence rate ratio [IRR]=0.812, P=.351), which was the primary outcome. The intervention group used more health care resources: they paid an increased number of visits to the nurse (IRR=1.73, P<.001), spent more time at the nurse reception (mean difference of 48.7 minutes, P<.001), and there was a greater number of telephone contacts between the nurse and intervention patients (IRR=3.82, P<.001 for nurse-induced contacts and IRR=1.63, P=.049 for patient-induced contacts). There were no statistically significant differences in patients’ clinical health status or in their self-care behavior. The technology received excellent feedback from the patient and professional side with a high adherence rate throughout the study.ConclusionsHome telemonitoring did not reduce the number of patients’ HF-related hospital days and did not improve the patients’ clinical condition. Patients in the telemonitoring group contacted the Cardiology Outpatient Clinic more frequently, and on this way increased the use of health care resources.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01759368","term_id":"NCT01759368"}}NCT01759368; http://clinicaltrials.gov/show/{"type":"clinical-trial","attrs":{"text":"NCT01759368","term_id":"NCT01759368"}}NCT01759368 (Archived by WebCite at http://www.webcitation.org/6UFxiCk8Z).     

A Clinical Trial for the Identification of Metabolic Biomarkers in Hashimoto’s Thyroiditis and in Psoriasis: Study Protocol

Hashimoto’s thyroiditis and psoriasis are inflammatory disorders that significantly impact patients’ quality of life, stressing the need for novel biomarkers of early diagnosis. This randomized clinical trial ({"type":"clinical-trial","attrs":{"text":"NCT04693936","term_id":"NCT04693936"}}NCT04693936) aims to identify Hashimoto’s thyroiditis’ and psoriasis’ metabolic biomarkers and to investigate the effect of environmental factors on the disease-related metabolic imprint and quality of life. Patients with Hashimoto’s thyroiditis, patients with psoriasis, and healthy individuals aged 18–60 will be recruited, enrolled according to eligibility criteria (medical history, clinical thyroid markers and the PASI score) and randomized to two groups. The intervention group will receive a combination of nutraceuticals for 6 months as part of a Mediterranean diet, and the control group will follow their usual diet. Data will be collected at baseline and the end of the study, including metabolite levels, lifestyle and anthropometric measurements, adherence to the Mediterranean diet (through the Mediterranean Diet Score) and disease-specific quality of life (through the Thyroid Patient Report Outcome for Hashimoto’s group, and the Dermatology Life Quality Index for the psoriasis group). This study will investigate metabolic biomarkers and related changes in Hashimoto’s thyroiditis and psoriasis and evaluate the association of metabolic changes with dietary factors and quality of life.     

Effects of Electrical Automatic Massage on Cognition and Sleep Quality in Alzheimer's Disease Spectrum Patients: A Randomized Controlled Trial

PurposeMuscle relaxation following electrical automatic massage (EAM) has been found to reduce fatigue, depression, stress, anxiety, and pain in individuals with various conditions. However, the effects of EAM have not been extensively explored in patients with Alzheimer''s disease (AD).Materials and MethodsHere, we conducted a randomized controlled study to evaluate the effects of EAM on the cognitive and non-cognitive functions of patients with AD spectrum disorders.ResultsWe found that EAM attenuated changes in attention-associated cognitive scores and subjective sleep quality relative to those in controls.ConclusionWhile further studies in a clinical setting are needed to support our findings, these encouraging results suggest that EAM may be an alternative therapy for the management of associated symptoms in AD (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT03507192","term_id":"NCT03507192"}}NCT03507192, 24/04/2018).     

Treating insomnia symptoms with medicinal cannabis: a randomized,crossover trial of the efficacy of a cannabinoid medicine compared with placebo

Study ObjectivesThis randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the safety and efficacy of 2 weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥3 months).MethodsCo-primary study endpoints were safety of the medication based on adverse event reporting and global insomnia symptoms (Insomnia Severity Index [ISI]). Secondary endpoints included: self-reported (sleep diary), actigraphy-derived, and polysomnography measurements of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE); and self-reported assessments of sleep quality (sSQ) and feeling rested upon waking. Adjusted mean differences between placebo and ZTL-101 were calculated.ResultsTwenty-three of 24 randomized participants (n = 20 female, mean age 53 ± 9 years) completed the protocol. No serious adverse events were reported. Forty mild, nonserious, adverse events were reported (36 during ZTL-101) with all but one resolving overnight or soon after waking. Compared to placebo, ZTL-101 decreased ISI (−5.07 units [95% CI: −7.28 to −2.86]; p = 0.0001) and self-reported SOL (−8.45 min [95% CI: −16.33 to −0.57]; p = 0.04) and increased self-reported TST (64.6 min [95% CI: 41.70 to 87.46]; p < 0.0001), sSQ (0.74 units [95% CI: 0.51 to 0.97]; p < 0.0001), and feeling of being rested on waking (0.51 units [95% CI: 0.24 to 0.78]; p = 0.0007). ZTL-101 also decreased actigraphy-derived WASO (−10.2 min [95% CI: −16.2 to −4.2]; p = 0.002), and increased actigraphy-derived TST (33.4 min [95% CI: 23.07 to 43.76]; p < 0.001) and SE (2.9% [95% CI: 2.0 to 3.8]; p = 0.005).ConclusionsTwo weeks of nightly sublingual administration of a cannabinoid extract (ZTL-101) is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms.Clinical TrialANZCTR; anzctr.org.au; ACTRN12618000078257.     

Comparing Effects in Regular Practice of E-Communication and Web-Based Self-Management Support Among Breast Cancer Patients: Preliminary Results From a Randomized Controlled Trial

BackgroundWhile Web-based interventions have been shown to assist a wide range of patients successfully in managing their illness, few studies have examined the relative contribution of different Web-based components to improve outcomes. Further efficacy trials are needed to test the effects of Web support when offered as a part of routine care.ObjectiveOur aim was to compare in regular care the effects of (1) an Internet-based patient provider communication service (IPPC), (2) WebChoice, a Web-based illness management system for breast cancer patients (IPPC included), and (3) usual care on symptom distress, anxiety, depression, (primary outcomes), and self-efficacy (secondary outcome). This study reports preliminary findings from 6 months’ follow-up data in a 12-month trial.MethodsWe recruited 167 patients recently diagnosed with breast cancer and undergoing treatment from three Norwegian hospitals. The nurse-administered IPPC allowed patients to send secure e-messages to and receive e-messages from health care personnel at the hospital where they were treated. In addition to the IPPC, WebChoice contains components for symptom monitoring, tailored information and self-management support, a diary, and communication with other patients. A total of 20 care providers (11 nurses, 6 physicians, and 3 social workers) were trained to answer questions from patients. Outcomes were measured with questionnaires at study entry and at study months 2, 4, and 6. Linear mixed models for repeated measures were fitted to compare effects on outcomes over time.ResultsPatients were randomly assigned to the WebChoice group (n=64), the IPPC group (n=45), or the usual care group (n=58). Response rates to questionnaires were 73.7% (123/167) at 2 months, 65.9 (110/167) at 4 months, and 62.3% (104/167) at 6 months. Attrition was similar in all study groups. Among those with access to WebChoice, 64% (41/64) logged on more than once and 39% (25/64) sent e-messages to care providers. In the IPPC group, 40% (18/45) sent e-messages. Linear mixed models analyses revealed that the WebChoice group reported significantly lower symptom distress (mean difference 0.16, 95% CI 0.06-0.25, P=.001), anxiety (mean difference 0.79, 95% CI 0.09-1.49, P=.03), and depression (mean difference 0.79, 95% CI 0.09-1.49, P=.03) compared with the usual care group. The IPPC group reported significant lower depression scores compared with the usual care group (mean difference 0.69, 95% CI 0.05-1.32, P=.03), but no differences were observed for symptom distress or anxiety. No significant differences in self-efficacy were found among the study groups.ConclusionsIn spite of practice variations and moderate use of the interventions, our results suggest that offering Web support as part of regular care can be a powerful tool to help patients manage their illness. Our finding that a nurse-administered IPPC alone can significantly reduce depression is particularly promising. However, the multicomponent intervention WebChoice had additional positive effects.

Trial Registration

Clinicaltrials.gov:{"type":"clinical-trial","attrs":{"text":"NCT00971009","term_id":"NCT00971009"}}NCT00971009; http://clinicaltrials.gov/show/{"type":"clinical-trial","attrs":{"text":"NCT00971009","term_id":"NCT00971009"}}NCT00971009 (Archived by WebCite at http://www.webcitation.org/6USKezP0Y).     

The Effect of Guided Web-Based Cognitive Behavioral Therapy on Patients With Depressive Symptoms and Heart Failure: A Pilot Randomized Controlled Trial

BackgroundDepressive symptoms, and the associated coexistence of symptoms of anxiety and decreased quality of life (QoL), are common in patients with heart failure (HF). However, treatment strategies for depressive symptoms in patients with HF still remain to be established. Internet-based cognitive behavioral therapy (ICBT), as guided self-help CBT programs, has shown good effects in the treatment of depression. Until now, ICBT has not been evaluated in patients with HF with depressive symptoms.ObjectiveThe aims of this study were to (1) evaluate the effect of a 9-week guided ICBT program on depressive symptoms in patients with HF; (2) investigate the effect of the ICBT program on cardiac anxiety and QoL; and (3) assess factors associated with the change in depressive symptoms.MethodsFifty participants were randomized into 2 treatment arms: ICBT or a Web-based moderated discussion forum (DF). The Patient Health Questionnaire-9 was used to measure depressive symptoms, the Cardiac Anxiety Questionnaire (CAQ) was used to measure cardiac-related anxiety, and the Minnesota Living with Heart Failure questionnaire was used to measure QoL. Data were collected at baseline and at follow-up at the end of the 9-week intervention. Intention-to-treat analysis was used, and missing data were imputed by the Expectation-Maximization method. Between-group differences were determined by analysis of covariance with control for baseline score and regression to the mean.ResultsNo significant difference in depressive symptoms between the ICBT and the DF group at the follow-up was found, [F(1,47)=1.63, P=.21] and Cohen´s d=0.26. Secondary within-group analysis of depressive symptoms showed that such symptoms decreased significantly in the ICBT group from baseline to the follow-up (baseline M=10.8, standard deviation [SD]=5.7 vs follow-up M=8.6, SD=4.6, t(24)=2.6, P=.02, Cohen´s d=0.43), whereas in the DF group, there was no significant change (baseline M=10.6, SD=5.0, vs follow-up M=9.8, SD=4.3, t(24)=0.93, P=.36. Cohen´s d=0.18). With regard to CAQ and QoL no significant differences were found between the groups (CAQ [d(1,47)=0.5, P=.48] and QoL [F(1,47)=2.87, P=.09]). In the ICBT group in the CAQ subscale of fear, a significant within-group decrease was shown (baseline M=1.55 vs follow-up M=1.35, P=.04). In the ICBT group, the number of logins to the Web portal correlated significantly with improvement in depressive symptoms (P=.02), whereas higher age (P=.01) and male sex (P=.048) were associated with less change in depressive symptoms. This study is underpowered because of difficulties in the recruitment of patients.ConclusionsGuided ICBT adapted for persons with HF and depressive symptoms was not statistically superior to participation in a Web-based DF. However, within the ICBT group, a statically significant improvement of depressive symptoms was detected.ClinicalTrialClinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01681771","term_id":"NCT01681771"}}NCT01681771; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01681771","term_id":"NCT01681771"}}NCT01681771 (Archived by WebCite at http://www.webcitation.org/6ikzbcuLN)