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).     

Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease: A Multicenter,Randomized, Phase IV Clinical Trial

PurposeOral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD.Materials and MethodsA seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels.ResultsSignificantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120.ConclusionDW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. {"type":"clinical-trial","attrs":{"text":"NCT02681952","term_id":"NCT02681952"}}NCT02681952).     

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.     

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     

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     

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.     

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).     

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).     

Long-Term Effects of an Internet-Mediated Pedometer-Based Walking Program for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial

BackgroundRegular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD). Interventions that promote PA and sustain long-term adherence to PA are needed.ObjectiveWe examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months.MethodsVeterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control. During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum. The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content. Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA. The primary outcome was health-related quality of life (HRQL) assessed by the St George’s Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count. Linear mixed-effect models assessed the effect of intervention over time. One participant was excluded from the analysis because he was an outlier. Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey.ResultsParticipants were 93.7% male (223/238) with a mean age of 67 (SD 9) years. At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count. Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12. Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001). Mean number of log-ins to the website each month also significantly decreased over the months of study (P<.001). The online community forum was used at least once during the study by 83.8% (129/154) of participants. Responses to questions assessing participants’ goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months.ConclusionsAn Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months. Waning pedometer adherence and website engagement by the intervention group were observed. Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA.ClinicalTrialClinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01102777","term_id":"NCT01102777"}}NCT01102777; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01102777","term_id":"NCT01102777"}}NCT01102777 (Archived by WebCite at http://www.webcitation.org/6iyNP9KUC)     

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     

Timely Diagnosis of Malalignment of the Distal Extremities Is Crucial in Morbidly Obese Juveniles

Background/AimsTo determine i) whether obesity in childhood can be related to malalignment of the distal extremities, ii) the proportion of genu valgum malalignment and abduction setting, and iii) the respective deviation dominance in children who are morbidly obese.Methods31 morbidly obese Caucasian children (16 males) recruited for the STYJOBS Study (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00482924","term_id":"NCT00482924"}}NCT00482924) with a mean age of 13.9 ± 0.5 years, a mean height of 162.3 ± 2.7 cm, a mean weight of 90.62 ± 5.0 kg, and a mean BMI of 33.8 ± 1.2 kg/m² were clinically examined using the Mikulicz line in order to assess load distribution on the knee joint. 21 participants received a whole-leg X-ray because of a clinically estimated malalignment.Results8/31 participants examined were diagnosed with genu valgum, 1/31 with genu varum, and 22/31 did not have any malalignment of the femur or tibia. The majority of genu valgum presentation was due to femoral deviation. Of those without malalignment, 4/22 participants had an abduction setting, while 2/22 showed an adduction of the leg.ConclusionGenu valgum as a predominant malalignment of the distal extremities is frequent in youth with morbid obesity. Timely guided correction of angular deformity of the knee seems pivotal in order to avoid osteotomy or osteoarthritis later in life.Key Words: Obesity, Children, Malalignment, Lower extremities, Temporary epiphyseodesis     

Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study

Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles.Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03238833","term_id":"NCT03238833"}}NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups.Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group.Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.     

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     

Aerobic and resistance exercise improve patient-reported sleep quality and is associated with cardiometabolic biomarkers in Hispanic and non-Hispanic breast cancer survivors who are overweight or obese: results from a secondary analysis

Study ObjectivesPoor sleep quality affects nearly one-third of breast cancer survivors and is associated with insulin resistance. The purpose of this secondary analysis was to examine the effects of a 16-week exercise intervention on patient-reported sleep quality among breast cancer survivors and assess whether changes in patient-reported sleep quality were associated with cardiometabolic biomarkers. We explored Hispanic ethnicity as a moderator of the effects of exercise on patient-reported sleep quality.MethodsBreast cancer survivors who were overweight or obese were randomized to exercise (n = 50) or usual care (n = 50). The 16-week intervention included aerobic and resistance exercise. Patient-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and biomarkers of cardiometabolic health were assessed at baseline and post-intervention. Within- and between-group differences were assessed using general linear models repeated-measures analyses of variance and mixed-model repeated-measure analysis, respectively. Associations between changes in PSQI and cardiometabolic biomarkers were computed using Pearson correlations. Linear mixed-models were used to evaluate effect modification by ethnicity.ResultsParticipants were 52 ± 10.4 years old, and over half were of Hispanic ethnicity. As compared to usual care, PSQI global scores improved significantly in the exercise group (mean between-group difference −2.2; 95% CI −3.2 to −0.6). Change in PSQI was inversely associated with changes in all cardiometabolic biomarkers (p < 0.01) among the exercise group. Ethnicity was found to moderate the effects of exercise training on global sleep quality (p < 0.001).ConclusionsAn aerobic and resistance exercise intervention effectively improved patient-reported sleep quality in breast cancer survivors. Hispanic ethnicity as a moderator showed greater improvement in patient-reported sleep indicating Hispanic versus non-Hispanic breast cancer survivors may derive larger sleep benefits.Clinical Trail Information{"type":"clinical-trial","attrs":{"text":"NCT01140282","term_id":"NCT01140282"}}NCT01140282.     

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)     

A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled Trial

Background

Bystander intervention approaches offer promise for reducing rates of sexual violence on college campuses. Most interventions are in-person small-group formats, which limit their reach and reduce their overall public health impact.

Objective

This study evaluated the efficacy of RealConsent, a Web-based bystander approach to sexual violence prevention, in enhancing prosocial intervening behaviors and preventing sexual violence perpetration.

Methods

A random probability sample of 743 male undergraduate students (aged 18 to 24 years) attending a large, urban university located in the southeastern United States was recruited online and randomized to either RealConsent (n=376) or a Web-based general health promotion program (n=367). Participants were surveyed online at baseline, postintervention, and 6-months postintervention. RealConsent was delivered via a password-protected Web portal that contained six 30-minute media-based and interactive modules covering knowledge of informed consent, communication skills regarding sex, the role of alcohol and male socialization in sexual violence, empathy for rape victims, and bystander education. Primary outcomes were self-reported prosocial intervening behaviors and sexual violence perpetration. Secondary outcomes were theoretical mediators (eg, knowledge, attitudes).

Results

At 6-month follow-up RealConsent participants intervened more often (P=.04) and engaged in less sexual violence perpetration (P=.04) compared to controls. In addition, RealConsent participants reported greater legal knowledge of sexual assault (P<.001), greater knowledge of effective consent (P<.001), less rape myths (P<.001), greater empathy for rape victims (P<.001), less negative date rape attitudes (P<.001), less hostility toward women (P=.01), greater intentions to intervene (P=.04), less hyper-gender ideology (P<.001), less positive outcome expectancies for nonconsensual sex (P=.03), more positive outcome expectancies for intervening (P<.001), and less comfort with other men’s inappropriate behaviors (P<.001).

Conclusions

Our results support the efficacy of RealConsent. Due to its Web-based format, RealConsent has potential for broad-based dissemination thereby increasing its overall public health impact on sexual violence.

Trial Registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01903876","term_id":"NCT01903876"}}NCT01903876; http://clinicaltrials.gov/show/{"type":"clinical-trial","attrs":{"text":"NCT01903876","term_id":"NCT01903876"}}NCT01903876 (Archived by WebCite at http://www.webcitation.org/6S1PXxWKt).     

Comparison of Abbott RealTime HCV Genotype II with Versant Line Probe Assay 2.0 for Hepatitis C Virus Genotyping

Genotyping and subtyping of 225 samples with hepatitis C virus (HCV) genotype 1, 2, 3, or 6 infection were done with Versant LiPA 2.0 and Abbott RealTime HCV Genotype (GT) II by using direct sequencing of the NS5B and 5′ untranslated regions as the reference standards. The concordance rates were >99.2% for genotypes and 96.1% for subtypes 1a and 1b. Both the Abbott RealTime and Versant LiPA assays can accurately determine hepatitis C virus genotypes. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00979979","term_id":"NCT00979979"}}NCT00979979.)     

Effects of a Web-Based Personalized Intervention on Physical Activity in European Adults: A Randomized Controlled Trial

BackgroundThe high prevalence of physical inactivity worldwide calls for innovative and more effective ways to promote physical activity (PA). There are limited objective data on the effectiveness of Web-based personalized feedback on increasing PA in adults.ObjectiveIt is hypothesized that providing personalized advice based on PA measured objectively alongside diet, phenotype, or genotype information would lead to larger and more sustained changes in PA, compared with nonpersonalized advice.MethodsA total of 1607 adults in seven European countries were randomized to either a control group (nonpersonalized advice, Level 0, L0) or to one of three personalized groups receiving personalized advice via the Internet based on current PA plus diet (Level 1, L1), PA plus diet and phenotype (Level 2, L2), or PA plus diet, phenotype, and genotype (Level 3, L3). PA was measured for 6 months using triaxial accelerometers, and self-reported using the Baecke questionnaire. Outcomes were objective and self-reported PA after 3 and 6 months.ResultsWhile 1270 participants (85.81% of 1480 actual starters) completed the 6-month trial, 1233 (83.31%) self-reported PA at both baseline and month 6, but only 730 (49.32%) had sufficient objective PA data at both time points. For the total cohort after 6 months, a greater improvement in self-reported total PA (P=.02) and PA during leisure (nonsport) (P=.03) was observed in personalized groups compared with the control group. For individuals advised to increase PA, we also observed greater improvements in those two self-reported indices (P=.006 and P=.008, respectively) with increased personalization of the advice (L2 and L3 vs L1). However, there were no significant differences in accelerometer results between personalized and control groups, and no significant effect of adding phenotypic or genotypic information to the tailored feedback at month 3 or 6. After 6 months, there were small but significant improvements in the objectively measured physical activity level (P<.05), moderate PA (P<.01), and sedentary time (P<.001) for individuals advised to increase PA, but these changes were similar across all groups.ConclusionsDifferent levels of personalization produced similar small changes in objective PA. We found no evidence that personalized advice is more effective than conventional “one size fits all” guidelines to promote changes in PA in our Web-based intervention when PA was measured objectively. Based on self-reports, PA increased to a greater extent with more personalized advice. Thus, it is crucial to measure PA objectively in any PA intervention study.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01530139","term_id":"NCT01530139"}}NCT01530139; http://clinicaltrials.gov/show/{"type":"clinical-trial","attrs":{"text":"NCT01530139","term_id":"NCT01530139"}}NCT01530139 (Archived by WebCite at: http://www.webcitation.org/6XII1QwHz)