Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Motivation and Treatment Credibility Predicts Dropout,Treatment Adherence,and Clinical Outcomes in an Internet-Based Cognitive Behavioral Relaxation Program: A Randomized Controlled Trial

BackgroundIn previous research, variables such as age, education, treatment credibility, and therapeutic alliance have shown to affect patients’ treatment adherence and outcome in Internet-based psychotherapy. A more detailed understanding of how such variables are associated with different measures of adherence and clinical outcomes may help in designing more effective online therapy.ObjectiveThe aims of this study were to investigate demographical, psychological, and treatment-specific variables that could predict dropout, treatment adherence, and treatment outcomes in a study of online relaxation for mild to moderate stress symptoms.MethodsParticipant dropout and attrition as well as data from self-report instruments completed before, during, and after the online relaxation program were analyzed. Multiple linear and logistical regression analyses were conducted to predict early dropout, overall attrition, online treatment progress, number of registered relaxation exercises, posttreatment symptom levels, and reliable improvement.ResultsDropout was significantly predicted by treatment credibility, whereas overall attrition was associated with reporting a focus on immediate consequences and experiencing a low level of intrinsic motivation for the treatment. Treatment progress was predicted by education level and treatment credibility, whereas number of registered relaxation exercises was associated with experiencing intrinsic motivation for the treatment. Posttreatment stress symptoms were positively predicted by feeling external pressure to participate in the treatment and negatively predicted by treatment credibility. Reporting reliable symptom improvement after treatment was predicted by treatment credibility and therapeutic bond.ConclusionsThis study confirmed that treatment credibility and a good working alliance are factors associated with successful Internet-based psychotherapy. Further, the study showed that measuring adherence in different ways provides somewhat different results, which underscore the importance of carefully defining treatment adherence in psychotherapy research. Lastly, the results suggest that finding the treatment interesting and engaging may help patients carry through with the intervention and complete prescribed assignments, a result that may help guide the design of future interventions.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02535598","term_id":"NCT02535598"}}NCT02535598; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02535598","term_id":"NCT02535598"}}NCT02535598 (Archived by WebCite at http://www.webcitation.org/6fl38ms7y).     

Asthma Management Using the Mobile Asthma Evaluation and Management System in China

PurposeAs stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma.MethodsIn this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT02917174","term_id":"NCT02917174"}}NCT02917174).ResultsBetween April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group.ConclusionsMobile asthma management can improve adherence and asthma control compared to traditional management.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02917174","term_id":"NCT02917174"}}NCT02917174     

Cyclic alternating pattern in children with obstructive sleep apnea and its relationship with adenotonsillectomy,behavior, cognition,and quality of life

Study ObjectivesTo determine in children with obstructive sleep apnea (OSA) the effect of adenotonsillectomy (AT) on the cyclic alternating pattern (CAP) and the relationship between CAP and behavioral, cognitive, and quality-of-life measures.MethodsCAP parameters were analyzed in 365 overnight polysomnographic recordings of children with mild-to-moderate OSA enrolled in the Childhood Adenotonsillectomy Trial (CHAT), randomized to either early AT (eAT) or watchful waiting with supportive care (WWSC). We also analyzed CAP in a subgroup of 72 children with moderate OSA (apnea–hypopnea index > 10) that were part of the CHAT sample. Causal mediation analysis was performed to determine the independent effect of changes in CAP on selected outcome measures.ResultsAt baseline, a higher number of A1 phases per hour of sleep was significantly associated with worse behavioral functioning (caregiver Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC): ρ = 0.24, p = 0.042; caregiver Conners’ Rating Scale Global Index: ρ = 0.25, p = 0.036) and lower quality of life (OSA-18: ρ = 0.27, p = 0.022; PedsQL: ρ = −0.29, p = 0.015) in the subgroup of children with moderate OSA, but not across the entire sample. At 7-months follow-up, changes in CAP parameters were comparable between the eAT and WWSC arms. CAP changes did not account for significant proportions of variations in behavioral, cognitive, and quality-of-life performance measures at follow-up.ConclusionsWe show a significant association between the frequency of slow, high-amplitude waves with behavioral functioning, as well as the quality of life in children with moderate OSA. Early AT in children with mild-to-moderate OSA does not alter the microstructure of nonrapid eye movement sleep compared with watchful waiting after an approximately 7-month period of follow-up.Clinical TrialThe study “A Randomized Controlled Study of Adenotonsillectomy for Children With Obstructive Sleep Apnea Syndrome” was registered at Clinicaltrials.gov (#{"type":"clinical-trial","attrs":{"text":"NCT00560859","term_id":"NCT00560859"}}NCT00560859).     

Efficacy and safety of calcium,magnesium, potassium,and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled,double-blind,randomized withdrawal study in adults with narcolepsy with cataplexy

Study ObjectivesEvaluate efficacy and safety of lower-sodium oxybate (LXB), a novel oxybate medication with 92% less sodium than sodium oxybate (SXB).MethodsAdults aged 18–70 years with narcolepsy with cataplexy were eligible. The study included a ≤30-day screening period; a 12-week, open-label, optimized treatment and titration period to transition to LXB from previous medications for the treatment of cataplexy; a 2-week stable-dose period (SDP); a 2-week, double-blind, randomized withdrawal period (DBRWP); and a 2-week safety follow-up. During DBRWP, participants were randomized 1:1 to placebo or to continue LXB treatment.ResultsEfficacy was assessed in 134 participants who received randomized treatment, and safety was assessed in all enrolled participants (N = 201). Statistically significant worsening of symptoms was observed in participants randomized to placebo, with median (first quartile [Q1], third quartile [Q3]) change in weekly number of cataplexy attacks from SDP to DBRWP (primary efficacy endpoint) in the placebo group of 2.35 (0.00, 11.61) versus 0.00 (−0.49, 1.75) in the LXB group (p < 0.0001; mean [standard deviation, SD] change: 11.46 [24.751] vs 0.12 [5.772]), and median (Q1, Q3) change in Epworth Sleepiness Scale score (key secondary efficacy endpoint) of 2.0 (0.0, 5.0) in the placebo group versus 0.0 (−1.0, 1.0) in the LXB group (p < 0.0001; mean [SD] change: 3.0 [4.68] vs 0.0 [2.90]). The most common treatment-emergent adverse events with LXB were headache (20.4%), nausea (12.9%), and dizziness (10.4%).ConclusionsEfficacy of LXB for the treatment of cataplexy and excessive daytime sleepiness was demonstrated. The safety profile of LXB was consistent with SXB.Clinical trial registration{"type":"clinical-trial","attrs":{"text":"NCT03030599","term_id":"NCT03030599"}}NCT03030599.     

Chronic kidney disease in propionic acidemia

PurposePropionic acidemia (PA) is a severe metabolic disorder characterized by multiorgan pathology, including renal disease. The prevalence of chronic kidney disease (CKD) in PA patients and factors associated with CKD in PA are not known.MethodsThirty-one subjects diagnosed with PA underwent laboratory and clinical evaluations through a dedicated natural history study at the National Institutes of Health (ClinicalTrials.gov identifier: NCT02890342).ResultsCross-sectional analysis of the creatinine-based estimated glomerular filtration rate (eGFR) in subjects with native kidneys revealed an age-dependent decline in renal function (P < 0.002). Among adults with PA, 4/8 (50%) had eGFR <60 mL/min/1.73 m². There was a significant discrepancy between eGFRs calculated using estimating equations based on serum creatinine compared with serum cystatin C (P < 0.0001). The tubular injury marker, plasma lipocalin-2, and plasma uric acid were strongly associated with CKD (P < 0.0001). The measured 24-hour creatinine excretion was below normal, even after adjusting for age, height, and sex.ConclusionCKD is common in adults with PA and is associated with age. The poor predictive performance of standard eGFR estimating equations, likely due to reduced creatine synthesis in kidney and liver, could delay the recognition of CKD and management of ensuing complications in this population.     

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

PurposeEndothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients.ResultsAch-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported.ConclusionAST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.     

Clinical Characteristics,Urinary Leukotriene E4 Levels,and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions

PurposeData on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes.MethodsThe clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were characterized based on the clinical history and drug provocation. The uLTE4 levels were measured at baseline, after aspirin provocation and after desensitization.ResultsMore than half of the patients (56.5%) presented with cutaneous symptoms (NSAID-exacerbated cutaneous disease), while one-third (33.7%) developed symptoms in at least 2 systems (NSAID-induced blended reactions; NIBR). Fifty-two patients underwent drug provocation and 59.6% of them yielded positive results. After drug provocation, a significant number of patients with confirmed NSAID cross-reactivity experienced clinical symptoms in more than one organ system. The uLTE4 levels at baseline were comparable between the NSAID-tolerant and NSAID-sensitive groups, but were substantially increased after aspirin provocation predominantly in NERD (983.4 pg/mg creatinine) and NIBR (501.0 pg/mg creatinine) compared to NSAID-tolerant subjects (122.1 pg/mg creatinine, P < 0.01 and 0.05, respectively). The uLTE4 levels were elevated after aspirin desensitization, although nasal polyposis and asthma were under control in 3 NERD and 3 NIBR subjects.ConclusionsNIBR is not uncommon among NSAID-sensitive patients in Thailand. The diagnostic value of basal uLTE4 levels was limited, but increased uLTE4 levels upon aspirin provocation suggest NSAID cross-reactivity with respiratory components. This study indicates that aspirin desensitization, if necessary, might be effective in both NERD and NIBR.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03849625","term_id":"NCT03849625"}}NCT03849625     

Demonstration of Autonomic Nervous Function and Cervical Sensorimotor Control After Cervical Lordosis Rehabilitation: A Randomized Controlled Trial

ContextSagittal-plane cervical spine alignment has emerged as one of the most important clinical outcomes in health care. Nevertheless, the quantity and quality of research on the role that cervical sagittal alignment plays in improving sensorimotor and autonomic nervous functions are limited.ObjectiveTo investigate the immediate and long-term effects of cervical lordosis restoration and correction of anterior head translation (AHT) on pain, disability, autonomic nervous system function, and cervical sensorimotor control in athletes with chronic nonspecific neck pain.DesignRandomized controlled clinical trial.SettingUniversity research laboratory.Patients or Other ParticipantsA total of 110 patients (59 males, 51 females) with chronic nonspecific neck pain and a defined hypolordotic cervical spine and AHT posture.Intervention(s)Patients were randomly assigned to the control or intervention group. Both groups received a multimodal program; the intervention group also received Denneroll cervical traction. Treatments were applied 3 times per week for 10 weeks.Main Outcome Measure(s)Outcome measures were cervical lordosis from C2 to C7, AHT, neck disability index, pain intensity, smooth-pursuit neck-torsion test, overall stability index, left- and right-rotation head repositioning accuracy, and amplitude and latency of skin sympathetic response. The measures were assessed 3 times: at baseline, after 10 weeks of treatment, and at 1-year follow-up.ResultsThe general linear model with repeated measures indicated group × time effects in favor of the intervention group for the following management outcomes: cervical lordosis, AHT, neck disability index, pain intensity, smooth-pursuit neck-torsion test, overall stability index, left- and right-rotation head repositioning accuracy, and amplitude and latency of the skin sympathetic response (P values < .001).ConclusionsRestoration of cervical sagittal alignment in the athletic population had a direct influence on pain, disability, autonomic nervous system dysfunction, and sensorimotor control. Our results should guide treatment planning for athletes and optimize their recovery time.Trial Registration NumberClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT04306640","term_id":"NCT04306640"}}NCT04306640     

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Background/AimsBesifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.MethodsPatients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).ResultsAmong 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.ConclusionsBSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: {"type":"clinical-trial","attrs":{"text":"NCT01937806","term_id":"NCT01937806"}}NCT01937806 (date: 10 Sep 2013).     

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).     

Effects of Wearable Powered Exoskeletal Training on Functional Mobility,Physiological Health and Quality of Life in Non-ambulatory Spinal Cord Injury Patients

BackgroundSpinal cord injury (SCI) is a serious clinical condition that impacts a patient''s physical, psychological, and socio-economic status. The aim of this pilot study was to evaluate the effects of training with a newly developed powered wearable exoskeleton (Hyundai Medical Exoskeleton [H-MEX]) on functional mobility, physiological health, and quality of life in non-ambulatory SCI patients.MethodsParticipants received 60 minutes of walking training with a powered exoskeleton 3 times per week for 10 weeks (total 30 sessions). The 6-minute walking test (6MWT) and timed-up-and-go test (TUGT) were performed to assess ambulatory function. The physiological outcomes of interest after exoskeleton-assisted walking training were spasticity, pulmonary function, bone mineral density, colon transit time, and serum inflammatory markers. Effects of walking training on subjective outcomes were estimated by the Korean version of the Falls Efficacy Scale—International and the 36-Item Short-Form Health Survey version 2.ResultsTen participants finished 30 sessions of training and could ambulate independently. No severe adverse events were reported during the study. After training, the mean distance walked in the 6MWT (49.13 m) was significantly enhanced compared with baseline (20.65 m). The results of the TUGT also indicated a statistically significant improvement in the times required to stand up, walk 3 m and sit down. Although not statistically significant, clinically meaningful changes in some secondary physiological outcomes and/or quality of life were reported in some participants.ConclusionIn conclusion, this study demonstrated that the newly developed wearable exoskeleton, H-MEX is safe and feasible for non-ambulatory SCI patients, and may have potential to improve quality of life of patients by assisting bipedal ambulation. These results suggest that the H-MEX can be considered a beneficial device for chronic non-ambulatory SCI patients.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT04055610","term_id":"NCT04055610"}}NCT04055610     

Preventive effects of an oral sorbent on nephropathy in rats

Circulating uremic substances are thought to be involved in the progression of chronic renal failure (CRF). An oral adsorbent AST-120 (Kremezin) is effective in removing circulating uremic toxins from the gastrointestinal tract, and retards the progression of CRF. AST-120 is widely used as an approved drug in Japan for the treatment of undialyzed uremic patients to delay the progression of CRF. AST-120 attenuates the progression of glomerular sclerosis and interstitial fibrosis in a variety of experimental rat models of CRF. However, the mechanism by which AST-120 delays the progression of CRF had not been clear. We have demonstrated that indoxyl sulfate, a dietary protein metabolite, is a circulating uremic toxin stimulating glomerular sclerosis and interstitial fibrosis, and that AST-120 decreases the serum and urine levels of indoxyl sulfate by adsorbing its precursor, indole, in the intestine. The administration of indoxyl sulfate to uremic rats stimulated the expression of transforming growth factor (TGF)-beta1, tissue inhibitor of metalloproteinase (TIMP)-1 and pro-alpha1(I)collagen in the kidneys. Further, the administration of AST-120 to uremic rats reduced the extent of glomerular sclerosis and interstitial fibrosis as well as the renal expression of TGF-beta1 and TIMP-1, by reducing the serum and urine levels of indoxyl sulfate. We propose the protein metabolite hypothesis that endogenous protein metabolites such as indoxyl sulfate play an important role in the progression of CRF, and that AST-120 is effective in retarding the progression of CRF by removing these protein metabolites through intestinal absorption.     

Cognitive effects of split and continuous sleep schedules in adolescents differ according to total sleep opportunity

Study ObjectivesWe compared the basic cognitive functions of adolescents undergoing split (nocturnal sleep + daytime nap) and continuous nocturnal sleep schedules when total sleep opportunity was either below or within the recommended range (i.e. 6.5 or 8 h).MethodsAdolescent participants (age: 15–19 year) in the 8-h split (n = 24) and continuous (n = 29) sleep groups were compared with 6.5-h split and continuous sleep groups from a previous study (n = 58). These protocols involved two baseline nights (9-h time-in-bed [TIB]), 5 nights of sleep manipulation, 2 recovery nights (9-h TIB), followed by a second cycle of sleep manipulation (3 nights) and recovery (2 nights). Cognitive performance, subjective sleepiness, and mood were evaluated daily; sleep was assessed using polysomnography.ResultsSplitting 6.5 h of sleep with a mid-afternoon nap offered a boost to cognitive function compared to continuous nocturnal sleep. However, when total TIB across 24 h increased to 8 h, the split and continuous sleep groups performed comparably in tests evaluating vigilance, working memory, executive function, processing speed, subjective sleepiness, and mood.ConclusionsIn adolescents, the effects of split sleep on basic cognitive functions vary by the amount of total sleep obtained. As long as the total sleep opportunity across 24 h is within the recommended range, students may fulfill sleep requirements by adopting a split sleep schedule consisting of a shorter period of nocturnal sleep combined with a mid-afternoon nap, without significant impact on basic cognitive functions.Clinical trial registration{"type":"clinical-trial","attrs":{"text":"NCT04044885","term_id":"NCT04044885"}}NCT04044885.     

Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower-Socioeconomic Status Community: A Randomized Controlled Trial

BackgroundAdoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging, especially for people living in lower-socioeconomic status (SES) communities. Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems.ObjectiveTo evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes.MethodsIn this noninferiority, pragmatic randomized controlled trial (RCT), patients from two primary care health centers in Toronto, Canada, with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of ≥7.3% (56.3 mmol/mol) were randomized to receive 6 months of health coaching with or without mobile phone monitoring support. We hypothesized that both approaches would result in significant HbA1c reductions, although health coaching with mobile phone monitoring would result in significantly larger effects. Participants were evaluated at baseline, 3 months, and 6 months. The primary outcome was the change in HbA1c from baseline to 6 months (difference between and within groups). Other outcomes included weight, waist circumference, body mass index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), positive and negative affect (Positive and Negative Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF-12]).ResultsA total of 138 patients were randomized and 7 were excluded for a substudy; of the remaining 131, 67 were allocated to the intervention group and 64 to the control group. Primary outcome data were available for 97 participants (74.0%). While both groups reduced their HbA1c levels, there were no significant between-group differences in change of HbA1c at 6 months using intention-to-treat (last observation carried forward [LOCF]) (P=.48) or per-protocol (P=.83) principles. However, the intervention group did achieve an accelerated HbA1c reduction, leading to a significant between-group difference at 3 months (P=.03). This difference was reduced at the 6-month follow-up as the control group continued to improve, achieving a reduction of 0.81% (8.9 mmol/mol) (P=.001) compared with a reduction of 0.84% (9.2 mmol/mol)(P=.001) in the intervention group. Intervention group participants also had significant decreases in weight (P=.006) and waist circumference (P=.01) while controls did not. Both groups reported improvements in mood, satisfaction with life, and quality of life.ConclusionsHealth coaching with and without access to mobile technology appeared to improve glucoregulation and mental health in a lower-SES, T2DM population. The accelerated improvement in the mobile phone group suggests the connectivity provided may more quickly improve adoption and adherence to health behaviors within a clinical diabetes management program. Overall, health coaching in primary care appears to lead to significant benefits for patients from lower-SES communities with poorly controlled type 2 diabetes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02036892","term_id":"NCT02036892"}}NCT02036892; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02036892","term_id":"NCT02036892"}}NCT02036892 (Archived by WebCite at http://www.webcitation.org/6b3cJYJOD)     

Implantable Cardioverter-defibrillator Utilization and Its Outcomes in Korea: Data from Korean Acute Heart Failure Registry

BackgroundThere are sparse data on the utilization rate of implantable cardioverter-defibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF).MethodsAmong 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients.ResultsAmong 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16–0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01–0.63], P = 0.015). According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06–0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069).ConclusionFollow-up data of this large, multicenter registry suggests a significant under-utilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01389843","term_id":"NCT01389843"}}NCT01389843     

Intraindividual variability in sleep schedule: effects of an internet-based cognitive-behavioral therapy for insomnia program and its relation with symptom remission

Study ObjectivesSleep schedule consistency is fundamental to cognitive-behavioral therapy for insomnia (CBT-I), although there is limited evidence suggesting whether it predicts treatment response. This analysis tested whether: (1) an Internet-based CBT-I program affects intraindividual variability (IIV) in sleep schedule and (2) sleep schedule IIV predicts insomnia symptom remission.MethodsThis secondary analysis compares participants (N = 303) randomized to an Internet-based CBT-I program (SHUTi—Sleep Healthy Using the Internet) or Internet-based patient education (PE). Participants reported daily bedtimes and rising times on 10 online sleep diaries collected over 2 weeks at baseline and 9-week post-intervention assessment. Participants completed the Insomnia Severity Index (ISI) at post-assessment and 6-month follow-up; symptom remission was defined by ISI < 8. Mixed effects location scale modeling was used to examine the effect of SHUTi on bedtime and rising time IIV; a novel two-staged analysis examined the effect of bedtime and rising time IIV on insomnia symptom remission.ResultsAt post-assessment, SHUTi participants reported about 30% less bedtime and 32% less rising time variability compared to PE (ps < 0.03). Bedtime and rising time IIV was not independently associated with likelihood of insomnia symptom remission at the subsequent time point (ps > 0.18), nor did sleep schedule IIV moderate treatment response (ps > 0.12).ConclusionsFindings demonstrate that an Internet-delivered CBT-I program can effectively increase users’ sleep schedule consistency relative to an educational control. This consistency, however, was not related to treatment outcome when defined by insomnia symptom remission, suggesting that enforcing rigid sleep schedules for patients may not be necessary for treatment success.Clinical Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT00328250","term_id":"NCT00328250"}}NCT00328250     

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).     

Blunted rest–activity rhythms link to higher body mass index and inflammatory markers in children

Study ObjectivesDisturbances of rest–activity rhythms are associated with higher body mass index (BMI) in adults. Whether such relationship exists in children is unclear. We aimed to examine cross-sectional associations of rest–activity rhythm characteristics with BMI z-score and obesity-related inflammatory markers in school-age children.MethodsParticipants included 411 healthy children (mean ± SD age 10.1 ± 1.3 years, 50.8% girls) from a Mediterranean area of Spain who wore wrist accelerometers for 7 consecutive days. Metrics of rest–activity rhythm were derived using both parametric and nonparametric approaches. Obesity-related inflammatory markers were measured in saliva (n = 121).ResultsIn a multivariable-adjusted model, higher BMI z-score is associated with less robust 24-h rest–activity rhythms as represented by lower relative amplitude (–0.16 [95% CI –0.29, –0.02] per SD, p = 0.02). The association between BMI z-score and relative amplitude persisted with additional adjustment for sleep duration, and attenuated after adjustment for daytime activity level. Less robust rest–activity rhythms were related to increased levels of several salivary pro-inflammatory markers, including C-reactive protein, which is inversely associated with relative amplitude (–32.6% [–47.8%, –12.9%] per SD), independently of BMI z-score, sleep duration, and daytime activity level.ConclusionBlunted rest–activity rhythms are associated with higher BMI z-score and salivary pro-inflammatory markers already at an early age. The association with BMI z-score seem to be independent of sleep duration, and those with pro-inflammatory markers further independent of BMI z-score and daytime activity. Novel intervention targets at an early age based on improving the strength of rest–activity rhythms may help to prevent childhood obesity and related inflammation.Clinical Trials Registration{"type":"clinical-trial","attrs":{"text":"NCT02895282","term_id":"NCT02895282"}}NCT02895282     

Memory performance following napping in habitual and non-habitual nappers

Study ObjectivesAfternoon naps benefit memory but this may depend on whether one is a habitual napper (HN; ≥1 nap/week) or non-habitual napper (NN). Here, we investigated whether a nap would benefit HN and NN differently, as well as whether HN would be more adversely affected by nap restriction compared to NN.MethodsForty-six participants in the nap condition (HN-nap: n = 25, NN-nap: n = 21) took a 90-min nap (14:00–15:30 pm) on experimental days while 46 participants in the Wake condition (HN-wake: n = 24, NN-wake: n = 22) remained awake in the afternoon. Memory tasks were administered after the nap to assess short-term topographical memory and long-term memory in the form of picture encoding and factual knowledge learning respectively.ResultsAn afternoon nap boosted picture encoding and factual knowledge learning irrespective of whether one habitually napped (main effects of condition (nap/wake): ps < 0.037). However, we found a significant interaction for the hippocampal-dependent topographical memory task (p = 0.039) wherein a nap, relative to wake, benefitted habitual nappers (HN-nap vs HN-wake: p = 0.003) compared to non-habitual nappers (NN-nap vs. NN-wake: p = 0.918). Notably for this task, habitual nappers’ performance significantly declined if they were not allowed to nap (HN-wake vs NN-wake: p = 0.037).ConclusionsContrary to concerns that napping may be disadvantageous for non-habitual nappers, we found that an afternoon nap was beneficial for long-term memory tasks even if one did not habitually nap. Naps were especially beneficial for habitual nappers performing a short-term topographical memory task, as it restored the decline that would otherwise have been incurred without a nap.Clinical Trial Information{"type":"clinical-trial","attrs":{"text":"NCT04044885","term_id":"NCT04044885"}}NCT04044885.