Pediatric Adenotonsillectomy Trial of Snoring
About
The Pediatric Adenotonsillectomy Trial for Snoring (PATS) study was a multi-centered, randomized, single-blinded, 12-month interventional study that compares the impact of adenotonsillectomy (AT) on measures of behavior, quality of life, and healthcare utilization in children aged 3-12 with mild sleep-disordered breathing (SDB), conducted from 2016 to 2022. This study aimed to clarify how to manage sleep-disordered breathing in children, focusing on several key issues: 1) assessing outcomes important to children and their families, including behavior, quality of life, and sleep disturbances; 2) exploring differences in treatment responses among children at higher risks for mild SDB, such as preschoolers, Black and Hispanic children, and those with asthma and/or obesity. Additionally, the study aimed to evaluate healthcare usage and investigate the impact of factors like secondhand smoke exposure, inadequate sleep, socioeconomic status, and family functioning on treatment effectiveness. Full details of the study design are found in the Supplemental material in the primary paper published in JAMA.
This study recruited children aged 3-12 who reported snoring at least 3 nights/week, AHI ≤ 3, no SpO2 < 90%, and tonsillar hypertrophy. Ineligibility was established based on the following criteria: history of previous tonsillectomy, recurrent tonsillitis, severe obesity with a BMI z-score greater than 3, presence of chronic health conditions other than asthma, significant developmental disability, Adaptive Behavior Assessment System (ABAS) score below 60, non-English speaking status, and intention to relocate from the area.
The study's coprimary endpoints are (1) change from baseline in executive behavior relating to self-regulation and organization skills as measured by the Behavior Rating Inventory of Executive Function (BRIEF) Global Composite Score (GEC); and (2) change from baseline in vigilance as measured on the Go-No-Go (GNG) signal detection parameter (d-prime).
The study's secondary endpoints include (click to expand):
Objective performance testing
- GNG inhibitory control d-prime
- Fine motor coordination: NIH-Toolbox 9-Hole Pegboard Dexterity Test
- Executive function: BRIEF 2/P meta-cognition and emotional regulation summary scores and subscales for parent and teacher reports
- Behavior: Child Behavior Checklist (CBCL) summary scale and subscores, parent and teacher ratings
- Attention: Conners 3 Short Form (caregiver and teacher versions) Global Index T score and subscales
- PSQ-SRBD Scale total score
- Sleepiness: Epworth Sleepiness Scale modified for children summary score and PSQ-SRBD sleepiness scale
- Generic: Pediatric Quality of Life Inventory total score and subscores
- Disease specific: Obstructive Sleep Apnea-18 (OSA-18) total score
- Measurements of weight; height; body mass index; waist, hip and neck circumferences
- Systolic, diastolic and mean blood pressure levels
- Medications, healthcare visits (scheduled and unscheduled), ascertained from caregiver reports, EMR surveillance, billing and pharmacy records and hospitalizations
The PATS dataset includes core demographic and polysomnography (PSG) data from the screening visit, and additional cognitive behavioral, quality of life, sleep disordered breathing symptoms, anthropometry, blood pressure, tobacco exposure and immunoglobulin titers, healthcare use, PSG and actigraphy from randomized children from baseline and follow-up visits. The PSG data were obtained from the standard laboratory-based overnight sleep study from the baseline clinic visit and 12-month follow-up visit. 7-day actigraphy was collected from children using Actiwatch 2 or Actiwatch Spectrum (Philips Respironics, Bend, OR) actigraph, and GT3X+ (ActiGraph, Pensacola, FL) as part of the baseline examinations from 2016 to early 2020 (Actigraphy data collection stopped due to the COVID-19 pandemic.) Behavior and neuropsychological assessments including Behavior Rating Inventory of Executive Function (BRIEF) and Go-No-Go (GNG) vigilance test were conducted at baseline and the 12-month follow up visit. Other demographic information and survey questionnaires such as Child Behavior Checklist (CBCL), Adaptive Behavior Assessment System, Allergies in Childhood (ISAAC) questionnaire, Epworth Sleepiness Scale (ESS), Pediatric Quality of Life Inventory (PedsQL), were collected from baseline and follow-up visits.
Important note on sample size: The core PATS dataset contains data on 920 children screened for the study, 459 children randomized, 306 children who underwent 12-month follow-up PSGs, and 298 children with baseline actigraphy. The NSRR PATS dataset was restricted to data from subjects who consented to future data sharing with investigators outside of the study team. Hence, the sample size included on NSRR is smaller than those reflected in existing PATS manuscripts. The NSRR PATS dataset contains data on 555 consented subjects and 330 randomized subjects.
Methods
Clinic visits
Participants were recruited from the following clinical sites:; Children's Hospital of Philadelphia, Philadelphia, PA; Children's Hospital of the King's Daughters, Norfolk, VA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Rainbow Babies and Children's Hospital, University Hospitals-Cleveland Medical Center, Cleveland, OH; University of Michigan Health System, Ann Arbor, MI; University of Texas Southwestern Medical Center, Dallas, TX. Note that Boston Children's Hospital, Boston MA was a study site, but data are not included as only one child was randomized from this site.
At baseline, 6-month and 12-month examinations, children were studied at a pediatric research center at a time when they were free of acute illness. At baseline, participants underwent neurobehavioral testing, PSG and assessment of patient-reported outcomes (sleepiness, quality of life and sleep quality), anthropometry, blood pressure, morning urine and blood sample collection. All measures are repeated at 6 and 12 months, except that the PSG is only repeated at 12 months. Neurobehavioral testing was conducted by staff blinded to treatment, trained and supervised by board-certified psychologists. Assessments at follow-up visits included clinical evaluation, anthropometry, neurobehavioral testing, and distribution of wrist actigraphy devices for in-home use for 7 days. The order of administration for child assessments were (1) 9-Hole Pegboard Dexterity Test; (2) GNG Test; and (3) Child Report version of PedsQL (as age appropriate). After March 2020, the 6-month examinations were simplified to address the challenges of in-person testing during the COVID-19 pandemic. Those 6-month follow-up visits were permitted to be conducted remotely, focusing on collection of the BRIEF primary outcome.
Randomization: At the end of the baseline visit, 231 participants were randomized to early adenotonsillectomy (eAT, within 4 weeks) while 228 Watchful Waiting with Supportive Care (WWSC). 188 and 196 children from the treatment arm had 6-month and 12-month visits, respectively. Comparable numbers of randomized children in the eAT and WWSC in the NSRR dataset are 167 and 163, respectively.
PSG collection
All children underwent full-night PSG by study-certified technicians using a standardized protocol and following the AASM Manual for the Scoring of Sleep and Associated Events Version 2.2 pediatric standards at the screening visit, at least a week before the baseline assessments. PSG equipment at the time existed at each site was used, which included an interface to an end-tidal CO2 monitor. To the extent possible, ancillary equipment and sensors were standardized across sites by requiring the use of a PATS-specific montage with defined sampling rates and digital specifications. Due to the different equipment used at each site, there may be some variations in some channels. Children were monitored by a certified sleep technician trained in pediatric PSG under the supervision of a lead technician who was certified at central training or another designee approved by the trial's Sleep Reading Center Chief Polysomnologist.
The PATS montage consisted of:
- 6 EEG sites: F3-M2, F4-M1, C3-M2, C4-M1, O1-M2, O2-M1
- Ground and reference electrodes: CZ, Fpz
- Bilateral electrooculograms (EOG): E1-M2, E2-M2
- Submental electromyography (EMG): LChin, RChin, CChin
- ECG with standard 3-lead precordial placement: ECG1, ECG2, ECG3
- Airflow via oronasal thermocouple
- Nasal pressure flow via nasal cannula
- Snoring vibration via tracheal (piezo) sensor
- Respiratory effort via chest and abdominal wall inductive plethysmography
- Capnography waveform and numeric values (End-tidal CO2)
- Pulse oximetry plethysmograph waveforms and numeric values (2 sec averaging mode preferred, with an acceptable maximum of 3 sec).
- Leg movements via bilateral EMG: LLeg1-LLeg2, RLeg1-RLeg2 (gold cups or single-use cups preferred, with piezoelectric sensors as acceptable alternatives).
- Body position
All PSG data were edited, scored and summarized at the Brigham and Women's Hospital Sleep Reading Center using well-developed quality assurance approaches. Intra- and inter-class correlations for key PSG parameters were monitored over time, and generally exceeded 0.90.
PSG scoring
The Compumedics software system was used to process and score all records. EDF signal and XML signals were later exported from the Compumedics E-Series system. Scoring was performed according to the AASM pediatric criteria by certified technologists blinded to all other study data at a central sleep reading center (Brigham and Women's Hospital).
The Apnea-Hypopnea Index (AHI) was defined as the sum of all obstructive and mixed apneas, plus hypopneas associated with a 30% reduction in airflow and either a > 3% desaturation or electroencephalographic arousal, divided by hours of total sleep time.
Actigraphy collection
Children were asked to wear a wrist actigraph on their non-dominant wrist for 7 days except when bathing or playing contact sports. Caregivers logged times in and out of bed and device removal during the same 7-day period using a sleep diary. The majority of studies utilized an Actiwatch 2 or Actiwatch Spectrum (Philips Respironics, Bend, OR) actigraph, although the GT3X+ (ActiGraph, Pensacola, FL) was used when other devices were unavailable.
Actigraphy scoring
The actigraphy data for each participant was annotated at the Sleep Reading Center at Brigham and Women's Hospital Sleep Medicine Epidemiology Program. After annotations, sleep–wake epochs were classified by Philips Actiware 6 (Philips) using 30-second epoch periods with a device-specific algorithm at medium sensitivity (40 counts for wake identification) or by using the ActiLife v6.13 (ActiGraph Inc; scored in 60-second epochs using the Sadeh algorithm) software.
- Sleep duration (24 hour and nocturnal): Average sleep duration during each 24-hour period was calculated as the duration of nocturnal sleep plus daytime naps.
- Sleep fragmentation index: The sleep fragmentation index was calculated as the sum of two proportions: the proportion of all epochs during the sleep period that were mobile (i.e., the activity count was 2 or greater [Philips] or y-axis counts greater than zero) and the proportion of all immobile bouts (i.e., consecutive epochs where the activity count was less than 2 during sleep that was 1 minute or less in duration [Philips] or when sleep was 1 minute or less [greater than zero]).
- Sleep efficiency: Sleep efficiency is the ratio of the time asleep to the time in bed.
Neurocognitive and behavioral assessment
Behavior and neuropsychological assessments were performed with a standardized protocol overseen by the study's Neurobehavioral Quality Control core. Research assistants were trainedby board-certified psychologists using videotaped sessions and individual feedback to facilitate accurate testing and scoring.
- Behavior Rating Inventory of Executive Function (BRIEF) - caregivers completed age-appropriate versions of the BRIEF (BRIEF–Preschool Edition for ages 2 to 4 and age 5 years if in preschool, or the BRIEF Second Edition for ages 6 to 18 and age 5 years in kindergarten; PAR Inc, Lutz, Florida), which assess behaviors associated with executive functioning (ability to self-regulate, pay attention, and organize in "real-world" situations).
- The Go-No-Go Continuous Performance Task (GNG/CPT) – a computer-based attention test developed for longitudinal studies of heterogenous samples of children ages 3 to 12 years.
- The National Institutes of Health Toolbox 9-Hole Pegboard Dexterity Test – a test to assess fine motor control.
- Child Behavior Checklist (CBCL) Parent Version (CBCL) and Teacher Report Form (TRF) – assess behavior.
- Conners 3rd Edition Short Form (Conners 3) (both the caregiver and teacher versions) – assess attention.
- Caregiver Adaptive Behavior Assessment System (ABAS-3) – assess adaptive behavior.
Other symptoms, quality of life and physical assessment
- Sleepiness: Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), Pediatric Sleep Questionnaire Sleep Related Breathing Disorder (SRBD)
- Asthma: International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, Composite Asthma Severity Index (CASI), Immunoglobulin (IgE).
- Quality of life: Pediatric Quality of Life Inventory (PedsQL), Obstructive Sleep Apnea-18 (OSA-18)
- Physical examination: anthropometrics, blood pressure
- Healthcare utilization: Monthly interviews with caregivers regarding adverse events (AEs), changes in health status, changes in medications, and healthcare visits. Electronic medical record (EMR) surveillance for hospitalizations, emergency room visits, medical or surgical procedures, consultation visits, medication prescriptions
- Family functioning: Family Assessment Device General Functioning subscale (FAD-GF12).
- Parenting style: Parenting Style Questionnaire.
- Parent perception of stress: Parenting Stress Index Short Form (PSI-4:SF).
- Health literacy: Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R).
- Influence of discrimination on health outcomes: Experiences of Discrimination.
- Second-hand smoke exposure: Urinary cotinine.
Data de-identification
All personally identifiable information (PII) has been removed from the data files by the NSRR team. For de-identification purposes, calendar dates were randomly offset within each subject by a random amount between -365 and +365 days.
Data overview
Covariates/phenotype datasets (CSV)
The covariate dataset files (pats-dataset-0.1.0.csv and pats-harmonized-dataset-0.1.0.csv) contain 1,461 rows each. The first column (public_subject_id) is the unique PATS subject identifier that can be linked with PSG signal filenames. There are four time points (timepoint) with repeated measures in the dataset: 0 = Screening, 1 = Baseline, 2 = 6-Month, 3 = 12-Month.
The dataset columns are described in the accompanying data dictionary files. The variables data dictionary file includes column names (id), labels (display names), descriptions, and other metadata. Categorical variables also include an associated "domain" (e.g., 1=Male, 0=Female), which are described in the domains data dictionary file.
The history of the covariate dataset and data dictionary files have been tracked on GitHub (https://github.com/nsrr/pats-data-dictionary).
The harmonized-dataset contains many of the most frequently used demographic and sleep variables. These variables were curated by the NSRR team.
Expand to see a selection of key harmonized variables:
| Variable | Label |
| nsrr_age | Subject age |
| nsrr_sex | Subject sex |
| nsrr_race | Subject race |
| nsrr_ethnicity | Subject ethnicity |
| nsrr_bmi | Body mass index (BMI) |
| nsrr_bp_systolic | Systolic blood pressure |
| nsrr_bp_diastolic | Diastolic blood pressure |
PSG signal files (EDF/XML)
| File type | File path | Description |
| Harmonized | /polysomnography | Files processed and harmonized (from the As is file set) to match NSRR signal and annotation naming standards. The processing steps have been documented here (https://gitlab-scm.partners.org/zzz-public/nsrr/-/tree/master/studies/pats). |
| As is | /original | Files exported from Compumedics Profusion after scoring at the Sleep Reading Center. Each recording contains an EDF signal file and XML scoring annotation file. |
Access and usage restrictions
The PATS dataset is only available for non-commercial use.
Citation and acknowledgement
When using this dataset, users must cite the following:
Users must include the following text in any Acknowledgements:
The Pediatric Adenotonsillectomy Trial for Snoring (PATS) study was supported by the U.S. National Institutes of Health, National Heart Lung and Blood Institute (1U01HL125307, 1U01HL125295). The National Sleep Research Resource was supported by the U.S. National Institutes of Health, National Heart Lung and Blood Institute (R24 HL114473, 75N92019R002).
Changelog
June 2024
- Make PATS dataset available for data requests
References
- PATS at ClinicalTrials.gov: ClinicalTrials.gov (NCT02562040)
- PATS GitHub Data Dictionary: https://github.com/nsrr/pats-data-dictionary
- PATS GitHub Documentation: https://github.com/nsrr/pats-documentation
Questions?
Please reach out to us at support@sleepdata.org or in the Forum if you have questions.