Impact of delaying high school start times on weight and related behaviors - the START study.

In the US, few adolescents get adequate school night sleep, largely due to early school start times. In the START study we aimed to test the following hypothesis: That following the implementation of later high school start times students have lesser longitudinal increases in body mass index (BMI) and shift to more healthful weight-related behaviors relative to students attending schools that retain early start times. The study enrolled a cohort of students (n = 2426) in five high schools in the Twin Cities, MN metro. Heights and weights were measured objectively, and surveys were administered annually from 9th through 11th grades (2016-2018). All study schools started early (either 7:30 am or 7:45 am) at baseline (2016). At follow-up 1 (2017) and continuing through follow-up 2 (2018), two schools delayed their start times by 50-65 min, while three comparison schools started at 7:30 am throughout the observation period. Using a difference-in-differences natural experiment design, we estimated differences in changes in BMI and weight-related behaviors over time between policy change and comparison schools. Students' BMIs increased in parallel in both policy change and comparison schools over time. However relative to changes in comparison schools after the start time shift, students in policy change schools had a modestly more healthful profile of weight-related behaviors - for instance they had a relatively greater probability of eating breakfast, having supper with their family, getting more activity, eating fast food less frequently, and eating vegetables daily. Later start times could be a durable, population-wide strategy that promotes healthful weight behaviors.

Pediatric sleep and pain: etiologies, consequences, and clinical considerations.

STUDY OBJECTIVES: To examine current evidence of the relationship between sleep and pain from the neonatal period through adolescence. This review serves as a critical review of the literature and of the needs for future research on pediatric sleep and pain. METHODS: The PubMed online database was queried from January 1, 1960, to March 1, 2020, producing 149 articles applicable to pain and sleep in the pediatric population. Of those, 97 articles were cited in this review with the key articles including over 3800 participants. RESULTS: The pediatric literature supports the relationship between poor sleep (both sleep efficiency and nighttime awakenings) and subsequent risk for pain, especially among children with chronic disease. The reverse effect of pain on sleep is not yet well delineated. The key moderating factors explored in the literature are pharmacologic and nonpharmacologic therapies, psychologic health, and the etiology of pain. There is evidence that both altered sleep and pain early in life impact neurodevelopment, as seen by changes in sleep structure in clinical studies and alterations in brain development in animal models. CONCLUSIONS: The complicated relationship between sleep and pain is critically important during pediatric development when alterations to a normal sleep structure can have a lifelong impact. It is becoming clear that sleep deprivation and poor sleep quality exacerbate pain. Further research is needed into the complex alterations of sleep in chronic pain conditions as well as treatments to improve sleep in pediatric care. CITATION: Morris EE, Howell MJ, Pickup E, Iber C, Wang SG. Pediatric sleep and pain: etiologies, consequences, and clinical considerations. J Clin Sleep Med. 2022;18(9):2281-2289.

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

STUDY OBJECTIVES: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial. METHODS: Participants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10). RESULTS: In 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73). CONCLUSIONS: Although subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486. CITATION: Pascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.

Weekend night vs. school night sleep patterns, weight status, and weight-related behaviors among adolescents.

OBJECTIVE: In this study, we examine associations between objectively measured weekend night vs. school night sleep patterns, weight status, and weight-related behaviors among adolescents. DESIGN: Cross-sectional study. SETTING: Five Minnesota high schools that started early (7:30 or 7:45 AM) in Spring 2016. PARTICIPANTS: Ninth grade students, ages 14.5-16 years (n = 284). MEASUREMENTS: Students completed surveys, had body measurements taken, and wore sleep (wrist) actigraphs for 1 week (n = 284). We examined weekend night-school night differences in sleep duration and sleep timing. We then assessed whether these factors were related to weight status and weight-related behaviors (eating behaviors, food consumption, physical activity, beverage consumption) using generalized linear mixed models. RESULTS: On average, students slept 1.5 hours (95% confidence interval 1.3-1.7) more and had a sleep midpoint 1.9 hours (1.8-2.1) later on weekend nights compared to school nights. Female students had larger increases in sleep duration on weekend nights than males but similar timing differences. Sleep duration differences were uncorrelated with sleep timing differences (r = 0.01). Neither duration nor timing differences were associated with overweight, obesity, or any of the eating behaviors we examined. However, sleeping longer on weekend nights than on school nights was associated with lower probability of being active 6-7 days per week (p = .02). CONCLUSIONS: Adolescents have substantial sleep duration and sleep timing differences on weekend nights vs. school nights. While these differences may not be associated with weight status or weight-related behaviors, they reflect the reality that most adolescents have schedules that restrict their sleep.

Association of Delaying School Start Time With Sleep-Wake Behaviors Among Adolescents.

PURPOSE: Few adolescents spend enough time asleep on school nights. This problem could be addressed by delaying high school start times, but does this translate to reduced prevalence of sleep-wake problems like awakening too early or feeling sleepy during the day? METHODS: The START study (n = 2,414) followed a cohort of students from five Minnesota high schools to evaluate impacts of school start time delays. Participants were enrolled in ninth grade (Baseline) when all schools started early (7:30 or 7:45 a.m.). At Follow-Up 1 (10th grade) and Follow-Up 2 (11th grade), two schools had delayed their start times by 50 and 65 minutes while three comparison schools started at 7:30 a.m. Six sleep-wake behaviors were assessed at all three time points via survey. Generalized estimating equation models were used to investigate changes in sleep-wake problems between policy change and comparison schools. RESULTS: The prevalence of sleep-wake problems at Baseline ranged from 11% for being late to class due to oversleeping to 48% for needing to be told to wake multiple times in the morning. Compared to students from comparison schools, students at policy change schools reported smaller increases in the prevalence of feeling sleepy daily and oversleeping and being late to class between 9th and 11th grade. After implementation of the delayed start, awakening too early was more common among students at policy change schools compared to the comparison schools. CONCLUSIONS: This longitudinal study provides evidence that delaying high school start times reduces daytime sleepiness and school tardiness.

Assessing Changes in Adolescents' Sleep Characteristics and Dietary Quality in the START Study, a Natural Experiment on Delayed School Start Time Policies.

BACKGROUND: Sleep duration, quality, and timing may influence dietary quality. In adults, poor dietary quality is a risk factor for numerous chronic diseases. It is unclear how these various sleep domains influence adolescents' diets because prior population-based studies have not effectively manipulated sleep, did not include objective sleep measures, and had short follow-up times. OBJECTIVES: The objectives of this study were to examine 1) how adolescent sleep characteristics relate to dietary quality; and 2) how delay in high school start times (which lengthened sleep duration) affects dietary quality over 2 y. METHODS: In the START study, adolescents (grades 9-11, n = 423) attending 5 high schools in the Minneapolis, Minnesota metropolitan area were annually assessed in 3 waves (2016-2018). At Baseline, all schools started "early" (07:30 or 07:45). From Follow-up 1 through Follow-up 2, 2 "policy change schools" shifted to later start times (to 08:20 and 08:50). Three "comparison schools" maintained their early start throughout. Sleep characteristics were measured with actigraphy. Mixed-effect regression models were used to examine cross-sectional and longitudinal associations of sleep characteristics with dietary quality, and school start time policy change with dietary quality change. RESULTS: Cross-sectionally, later sleep midpoint and onset were associated with dietary quality scores 1.6-1.7 lower (both P < 0.05). However, no prospective associations were observed between sleep characteristics and dietary quality in longitudinal models. Shifting to later school start time tended to be associated with a 2.4-point increase in dietary quality score (P = 0.09) at Follow-up 1, but was not associated with change in dietary quality scores at Follow-up 2 (P = 0.35). CONCLUSIONS: High school students attending delayed-start schools maintained better dietary quality than students in comparison schools; however, differences were not statistically significant. Overall study findings highlight the complexity of the relation between sleep behavior and diet in adolescence.

EHR Integration of PAP Devices in Sleep Medicine Implementation in the Clinical Setting.

Positive airway pressure (PAP) therapy integration is a component of electronic health record (EHR) sleep medicine optimization. EHR optimization facilitates telehealth in continuous care population health. A coordinated care plan can leverage early telehealth interventions.

Association of Delaying School Start Time With Sleep Duration, Timing, and Quality Among Adolescents.

Importance: Sleep is a resource that has been associated with health and well-being; however, sleep insufficiency is common among adolescents. Objective: To examine how delaying school start time is associated with objectively assessed sleep duration, timing, and quality in a cohort of adolescents. Design, Setting, and Participants: This observational cohort study took advantage of district-initiated modifications in the starting times of 5 public high schools in the metropolitan area of Minneapolis and St Paul, Minnesota. A total of 455 students were followed up from grade 9 (May 3 to June 3, 2016) through grade 11 (March 15 to May 21, 2018). Data were analyzed from February 1 to July 24, 2019. Exposures: All 5 participating schools started early (7:30 am or 7:45 am) at baseline (2016). At follow-up 1 (2017) and continuing through follow-up 2 (2018), 2 schools delayed their start times by 50 and 65 minutes, whereas 3 comparison schools started at 7:30 am throughout the observation period. Main Outcomes and Measures: Wrist actigraphy was used to derive indices of sleep duration, timing, and quality. With a difference-in-difference design, linear mixed-effects models were used to estimate differences in changes in sleep time between delayed-start and comparison schools. Results: A total of 455 students were included in the analysis (among those identifying sex, 225 girls [49.5%] and 219 boys [48.1%]; mean [SD] age at baseline, 15.2 [0.3] years). Relative to the change observed in the comparison schools, students who attended delayed-start schools had an additional mean 41 (95% CI, 25-57) objectively measured minutes of night sleep at follow-up 1 and 43 (95% CI, 25-61) at follow-up 2. Delayed start times were not associated with falling asleep later on school nights at follow-ups, and students attending these schools had a mean difference-in-differences change in weekend night sleep of -24 (95% CI, -51 to 2) minutes from baseline to follow-up 1 and -34 (95% CI, -65 to -3) minutes from baseline to follow-up 2, relative to comparison school participants. Differences in differences for school night sleep onset, weekend sleep onset latency, sleep midpoints, sleep efficiency, and the sleep fragmentation index between the 2 conditions were minimal. Conclusions and Relevance: This study found that delaying high school start times could extend adolescent school night sleep duration and lessen their need for catch-up sleep on weekends. These findings suggest that later start times could be a durable strategy for addressing population-wide adolescent sleep deficits.

The START study: An evaluation to study the impact of a natural experiment in high school start times on adolescent weight and related behaviors.

BACKGROUND: Research has shown that early high school start times, which are asynchronous with adolescent biology, are one of the most significant obstacles to youth being able to net sufficient sleep. Given that adolescence is a critical period that sets the stage for long-term obesity risk behavior patterns, there is an need to understand the obesity-related implications of increased sleep as a result of intervention and policy changes. METHODS: We evaluated a community-based natural experiment in school start time policy modification when several Minneapolis-St. Paul, MN metro area school districts shifted to later school start times in Fall 2016. We collected data on student weight and related risks (via paper survey, objective weight and height measurement, dietary recall, and sleep actigraphy) before and after two districts (two high schools) shifted their start times later and in a comparison district (three high schools) which kept their start times early (7:30am) through the course of the study. Our specific aims were: 1) Determine how a shift to a later high school start time relates to objectively measured weight change over time. 2) Identify the relationship between school start times and obesity-related behaviors over time.At baseline we had 2,133 returned surveys (93% participation) and 2,037 (86% participation) objective height/weight measurements from 9th grade students (class of 2019) in the five schools. The sample was 87.7% white, 12.8% reported qualifying for free/reduced price lunch (a measure of lower socio-economic status), and the mean age was 15.2 (SD=0.35) years. DISCUSSION: The products of this research will clarify causal connections between sleep and obesity among adolescents as well as provide evidence for whether a school start time policy can minimize unhealthy weight gain.

Correlates of short sleep duration among adolescents.

INTRODUCTION: Short sleep duration is exceedingly common among adolescents and has implications for healthy youth development. We sought to document associations between adolescents' sleep duration and characteristics of their schedules, behaviors, and wellbeing. METHODS: We used data from the baseline wave (9th grade year) of the START study, a cohort of 2134 students in five Minnesota high schools to assess how self-reported sleep duration was associated with the prevalence of time-use characteristics (i.e. activity schedules, screen use), sleep-wake problems (i.e. trouble waking in the morning, falling asleep in class, etc.), and risk of depression. RESULTS: Shorter sleep duration was associated with various behaviors including greater computer/screen time and screen use after bed, a lower probability of doing homework, participation in sports doing chores on school nights, and reporting that it takes at least 20 min to fall asleep on school days (p < 0.05). Suboptimal sleep duration was also associated with a higher probability of all reported sleep-wake problems as well as higher risk of depressive symptoms (p < 0.05). CONCLUSIONS: Given that getting an optimal amount of sleep can protect youth from risk and promote healthy youth development, it is critical that we gain a greater understanding of correlates and consequences of short sleep duration in order to develop a sleep-friendly culture for youth.

Sleep Duration and Weight-Related Behaviors among Adolescents.

Background: Insufficient sleep is widespread among adolescents and has consequences that extend far beyond hampering day-to-day functioning. It may influence eating and physical activity patterns and be an important determinant of adolescent overweight/obesity status. Methods: We assessed how self-reported sleep duration on school nights was associated with weight-related behaviors (eating, diet, and physical activity) and overweight/obesity at the baseline wave (ninth grade year) of the START study (n = 2134). Results: Fifteen percent of our sample reported optimal sleep duration (8.5-10.0 hours); nonwhites, participants of lower socioeconomic status, and girls were at greater risk for insufficient sleep. Suboptimal sleep was associated with various poor weight-related behaviors such as increased sugar-sweetened beverage consumption, decreased vegetable consumption, and decreased breakfast eating (p < 0.001). Fewer hours of sleep were also associated with less physical activity and an increased likelihood of obesity (p = 0.02 for both associations). Conclusions: The influence of adolescent sleep insufficiency on diet and activity could impact childhood obesity and following chronic disease risk especially if lack of sleep sets the stage for enduring, lifelong, poor, weight-related behavior patterns.

Diagnosed Sleep Apnea and Cardiovascular Disease in Atrial Fibrillation Patients: The Role of Measurement Error from Administrative Data.

BACKGROUND: Atrial fibrillation and obstructive sleep apnea are common conditions, but little is known about obstructive sleep apnea and cardiovascular risk among atrial fibrillation patients. METHODS: Using the Truven Health MarketScan databases, we constructed a prospective cohort of atrial fibrillation patients from 2007 to 2014. Atrial fibrillation, obstructive sleep apnea, stroke, myocardial infarction, and confounders were defined using the International Classification of Disease-9-CM codes. We matched individuals with an obstructive sleep apnea diagnosis with up to five individuals without a diagnosis by age, sex, and enrollment date. Cox proportional hazards models adjusted for confounders and high-dimensional propensity scores. We included migraines as a control outcome. Bias analysis used published sensitivities and specificities to generate rate ratios adjusted for obstructive sleep apnea misclassification. RESULTS: We matched 56,969 individuals with an obstructive sleep apnea diagnosis to 323,246 without. During a mean follow-up of 16 months, 3234 incident strokes and 4639 incident myocardial infarctions occurred. After adjustment, obstructive sleep apnea diagnosis was strongly associated with reduced risk of incident stroke (hazard ratio = 0.48, 95% confidence interval = 0.43, 0.53) and myocardial infarction (0.40, [0.37, 0.44]) and a smaller reduced risk of migraines (0.82, [0.68, 0.99]). Bias analysis produced wide-ranging or inestimable rate ratios adjusted for misclassification of obstructive sleep apnea. CONCLUSIONS: Obstructive sleep apnea diagnosis in atrial fibrillation patients was strongly associated with reduced risk of incident cardiovascular disease. We discuss misclassification, selection bias, and residual confounding as potential explanations.

Smartphone-based delivery of oropharyngeal exercises for treatment of snoring: a randomized controlled trial.

PURPOSE: Upper airway exercises for snoring treatment can be effective but difficult to administer and monitor. We hypothesized that a brief, relatively simple daily upper airway exercise regimen, administered by a smartphone application, would reduce snoring and encourage compliance. METHODS: Targeted vowel sounds causing tongue base movements were incorporated into a voice-controlled smartphone game application. Participants with habitual snoring, apnea hypopnea index (AHI) ≤ 14 events/h, and BMI ≤ 32 kg/m2 were randomly assigned to perform 15 min of daily gameplay (intervention group) or 5 s of daily voice recording (control group) and to audio record their snoring for 2 nights/week for up to 12 weeks. Sounds above 60 dB were extracted from recordings for snore classification with machine learning support vector machine classifiers. RESULTS: Sixteen patients (eight in each group) completed the protocol. Groups were similar at baseline in gender distribution (five males, three females), mean BMI (27.5 ± 3.8 vs 27.4 ± 3.8 kg/m2), neck circumference (15.1 ± 1.6 vs 14.7 ± 1.7 in.), Epworth Sleepiness Score (8 ± 3.5 vs 7 ± 4.0), and AHI (9.2 ± 4.0 vs 8.2 ± 3.2 events/h). At 8 weeks, the absolute change in snoring rate (> 60 dB/h) was greater for the intervention group than the control group (- 49.3 ± 55.3 vs - 6.23 ± 23.2; p = 0.037), a 22 and 5.6% reduction, respectively. All bed partners of participants in the intervention group reported reduced snoring volume and frequency, whereas no change was reported for the control group. CONCLUSIONS: Smartphone application-administered upper airway training reduces objective and subjective snoring measures and improves sleep quality. TRIAL REGISTRATION: ClinicalTrials.gov ; no.: NCT03264963; URL: www.clinicaltrials.gov.

Joint effects of OSA and self-reported sleepiness on incident CHD and stroke.

BACKGROUND: Although excessive daytime sleepiness (EDS) is a common symptom of obstructive sleep apnea (OSA), and both EDS and OSA have separately been associated with increased risk of cardiovascular disease (CVD), their joint association with CVD risk is unknown. METHODS: Among 3874 Sleep Heart Health Study (SHHS) participants without prevalent CVD, moderate to severe OSA was defined by an apnea hypopnea index (AHI) ≥ 15 on an in-home polysomnography. EDS was defined as an Epworth Sleepiness Scale score ≥11. Incident CVD events included total CVD events (coronary heart disease (CHD) and stroke), as well as CHD and stroke separately. Cox proportional hazards models adjusted for age, sex, alcohol, smoking, and body mass index. RESULTS: Compared to those with AHI <15, the hazard ratios (95% CI) for the association of moderate-severe OSA (AHI ≥15) were as follows: CVD 1.06 (0.85-1.33); CHD 1.08 (0.85-1.33); and stroke 1.18 (0.75-1.84). Weak associations between EDS and CVD risk = [1.22 (1.01-1.47)] and CHD risk [1.25 (1.02-1.53)] were present, however there were none for stroke risk [1.10 (0.75-1.63)]. When jointly modeled, both AHI ≥15 and EDS (compared with having AHI <15 and no EDS) was associated with HRs of 1.26 (0.91-1.73) for CVD, 1.24 (0.87-1.75) for CHD and 1.49 (0.78-2.86) for stroke. There were no statistically significant interactions between daytime sleepiness and OSA on the multiplicative or additive scales. CONCLUSIONS: Having both EDS and moderate-severe OSA was not associated with an increased risk of CVD in the SHHS data.

A brief tool to differentiate factors contributing to insomnia complaints.

OBJECTIVE: A complaint of insomnia may have many causes. A brief tool examining contributing factors may be useful for nonsleep specialists. This study describes the development of the Insomnia Symptoms Assessment (ISA) for examining insomnia complaints. METHOD: ISA questions were designed to identify symptoms that may represent 1 of 8 possible factors contributing to insomnia symptoms, including delayed sleep phase syndrome (DSPS), shift work sleep disorder (SWSD), obstructive sleep apnea (OSA), mental health, chronic pain, restless leg syndrome (RLS), poor sleep hygiene, and psychophysiological insomnia (PI). The ISA was completed by 346 new patients. Patients met with a sleep specialist who determined primary and secondary diagnoses. RESULTS: Mean age was 45 (18-85) years and 51% were male. Exploratory factor analysis (n = 217) and confirmatory factor analysis (n = 129) supported 5 factors with good internal consistency (Cronbach's alpha), including RLS (.72), OSA (.60), SWSD (.67), DSPS (.64), and PI (.80). Thirty percent had 1 sleep diagnosis with a mean of 2.2 diagnoses per patient. No diagnosis was entered for 1.2% of patients. The receiver operating characteristics were examined and the area under the curves calculated as an indication of convergent validity for the primary diagnosis (N = 346) were .97 for SWSD, .78 for OSA, .67 for DSPS, .54 for PI, and .80 for RLS. CONCLUSION: The ISA demonstrated good internal consistency and corresponds well to expert diagnoses. Next steps include setting sensitivity/specificity cutoffs to suggest initial treatment recommendations for use in other settings. (PsycINFO Database Record

An Economic Evaluation of Home Versus Laboratory-Based Diagnosis of Obstructive Sleep Apnea.

STUDY OBJECTIVES: We conducted an economic analysis of the HomePAP study, a multicenter randomized clinical trial that compared home-based versus laboratory-based testing for the diagnosis and management of obstructive sleep apnea (OSA). DESIGN: A cost-minimization analysis from the payer and provider perspectives was performed, given that 3-mo clinical outcomes were equivalent. SETTING: Seven academic sleep centers. PARTICIPANTS: There were 373 subjects at high risk for moderate to severe OSA. INTERVENTIONS: Subjects were randomized to either home-based limited channel portable monitoring followed by unattended autotitration with continuous positive airway pressure (CPAP), versus a traditional pathway of in-laboratory sleep study and CPAP titration. MEASUREMENTS AND RESULTS: From the payer perspective, per subject costs for the laboratory-based pathway were $1,840 (95% confidence interval [CI] $1,660, $2,015) compared to $1,575 (95% CI $1,439, $1,716) for the home-based pathway under the base case. Costs were $264 (95% CI $39, $496, P = 0.02) in favor of the home arm. From the provider perspective, per subject costs for the laboratory arm were $1,697 (95% CI $1,566, $1,826) compared to $1,736 (95% CI $1,621, $1,857) in the home arm, for a difference of $40 (95% CI -$213, $142, P = 0.66) in favor of the laboratory arm under the base case. The provider operating margin was $142 (95% CI $85, $202,P < 0.01) in the laboratory arm, compared to a loss of -$161 (95% CI -$202, -$120, P < 0.01) in the home arm. CONCLUSIONS: For payers, a home-based diagnostic pathway for obstructive sleep apnea with robust patient support incurs fewer costs than a laboratory-based pathway. For providers, costs are comparable if not higher, resulting in a negative operating margin. CLINICALTRIALSGOV IDENTIFIER: NCT00642486.