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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL105999-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Michigan Technological University | OTHER |
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Obstructive sleep-disordered breathing (SDB) affects 2-3% of children and may lead to problems with nighttime sleep and daytime behavior, learning, sleepiness, and mood. Adenotonsillectomy (AT) is the second most common surgical procedure in children. It is now performed more often for suspected SDB than for any other indication. However, recent studies indicate that many if not most children still have SDB after AT, and many still have learning or behavioral problems associated with SDB. The goals of this study are: (1) to assess the extent that behavior, cognition, and sleepiness in children can improve with Continuous positive airway pressure (CPAP) treatment after AT, and (2) to identify which patients stand to gain most from post-operative assessment and treatment.
Obstructive sleep-disordered breathing (SDB) affects at least 2-3% of children and may have substantial adverse impact on behavior and cognition. Adenotonsillectomy (AT), the second most common surgical procedure in children, is now performed more often for suspected SDB than for any other indication. However, recent studies among an increasingly obese population now show something alarming: many if not most children still have SDB after AT, and many still suffer from residual neurobehavioral morbidity. Furthermore, the investigators' ongoing, 12-year, NIH-funded research has shown that standard preoperative polysomnographic measures of SDB do not consistently predict post-AT improvement in behavior and cognition. This may arise in part because many children after AT still have SDB, and because linear relationships between standard SDB measures and neurobehavioral morbidity may not exist. Even at subtle levels, SDB may promote significant neurobehavioral morbidity. Some have suggested that polysomnography may be more important after AT than before AT. However, in practice few children receive polysomnography before AT, and even fewer after AT, when continuous positive airway pressure (CPAP) could still provide definitive relief from SDB. Preliminary data from our group suggest that CPAP after AT is well-tolerated by most children and may provide significant benefit. However, virtually no published evidence exists to address critical clinical questions: which children benefit most from CPAP after AT; what role can clinical symptoms or polysomnography play in that determination; and what neurobehavioral gains are achieved by CPAP after AT?
The investigators therefore will undertake a highly practical, clinical study with two main goals: (1) to assess the extent that behavior, cognition, and sleepiness in children can improve with CPAP after AT, and (2) to identify which patients stand to gain most from post-operative assessment and treatment. This research will use reversible SDB-related neurobehavioral morbidity as the criteria by which to judge the utility of clinical symptoms and polysomnography in identification of candidates for CPAP after AT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CPAP treatment | Experimental | Children randomized to this arm will receive 6 months of CPAP (or BPAP) treatment, beginning at approximately 4 months after AT, in addition to standard of care. For analysis purposes those children who were non-adherent (CPAP use <4 hours per night) vs. adherent (CPAP use at least 4 hours per night) will be analyzed separately. |
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| No CPAP treatment | Other | Children randomized to this comparison arm will not be treated with CPAP or BPAP, but will be followed for approximately 10 months after AT while receiving standard of care. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPAP treatment | Procedure | 6 months of treatment with PAP (CPAP or BPAP) |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Behavioral Index After 6 Months of CPAP or No-CPAP | The sum of the T-scores of The Conners' Parent Rating Scales (CPRS-R:L, ADHD index) and the Child Behavior Checklist (CBCL, Attention Deficit/Hyperactivity Problems) are used to construct the primary study outcome measure Behavioral Index. Behavioral index is a T score (adjusted for age and gender) with a range of "<10" to ">90" - where higher scores mean worse behavior and lower scores mean better behavior, so a negative change score represents an improvement in behavior. T-scores with a mean of 50 and SD of 10 are computed. | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cognition as Shown by NIH Toolbox Composite Score | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40 and Maximum value 160. Higher scores are better | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| Change in Sleepiness as Measured by Epworth Sleepiness Scale |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cognition as Measured by Fluid Cognition Scores | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40, Maximum value 160. Higher scores are better | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| Change in Cognition After AT as Shown by Academic Achievement |
Inclusion Criteria:
Exclusion Criteria:
No siblings of children already enrolled in the study,
Children who expect to have another surgery (in addition to AT) during the period of participation in this study,
Neurological, psychiatric, or medical conditions, or social factors that may affect test results, prevent children from returning for required study visits, or interfere with the study treatment, or
Certain medications that affect sleepiness or alertness, for example:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald D. Chervin, MD, MS | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Health System | Ann Arbor | Michigan | 48109 | United States |
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Of 120 consented, 105 were randomized to CPAP or control. (Of the 15 who weren't randomized, 8 were lost to follow up; the other withdrew for various reasons)
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Group (Surgery Only - no CPAP) | The participants who were not assigned to CPAP |
| FG001 | CPAP After Surgery (Adherent) | Those participants assigned to CPAP who had at least 4 hours of electronically recorded CPAP use per night |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 16, 2018 |
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| No CPAP treatment | Other | Children randomized to the comparison group will receive routine care |
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Epworth Sleepiness Scale scores range from 0 to 24 where higher scores mean greater sleepiness. |
| assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | Multiple Sleep Latency Test (MSLT) is an objective measure of sleepiness determined by measure of brain waves and other physiological signals over a 30 minute period. This is measured for five 30 minute periods across the day and average latency to sleep for each participant across those times were used to calculate the mean sleep latency. The score is measured in how quickly one would fall asleep, measured in minutes, so a negative number of minutes in the change score means that participants fell asleep more quickly than previously. | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| Change in Quality of Life as Measured by Peds QL | Peds-QL is a quality of life symptom measurement with a score range of 0 to 100. Higher scores are better quality of life | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| CPAP Adherence as Measured by Number of Participants Who Used the CPAP Consistently. | CPAP adherence data will be downloaded from CPAP machines. It is defined for this study as using the CPAP machine for at least an average of 4 hours per night during the last 60 days of the assignment. | Starting at 4 months after AT and continuing through 10 months after AT |
Academic achievement mean score is a standardized score with a mean of 100 and SD 15. Minimum value 40 and Maximum value 160. Higher scores are better |
| assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
| FG002 | CPAP After Surgery (Non-adherent) | Those participants assigned CPAP who did not have at least 4 hours of electronically recorded CPAP use per night. |
| Crossed Over to Control |
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| Had CPAP Titration |
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| Initiated CPAP Treatment at Home |
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| Completed as a Control |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Group (Surgery Only - no CPAP) | The participants who were not assigned to CPAP |
| BG001 | CPAP After Surgery (Adherent) | Those participants assigned to CPAP who had at least 4 hours of electronically recorded CPAP use per night |
| BG002 | CPAP After Surgery (Non-adherent) | Those participants assigned CPAP who did not have at least 4 hours of electronically recorded CPAP use per night. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Behavioral Index | Computation of T-scores (mean of 50, SD of 10). Minimum value < 10, maximum value >90, SD=10. Higher scores indicate worse behavior | Behavioral Index was not available for one control | Mean | Standard Deviation | units on a scale (T-Score) |
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| NIH Toolbox Age adjusted composite score | Scores are reported as Standardized scores with a mean of 100, and SD of 15. Minimum value 40, maximum value 160. Higher scores are good | Subject ages too young for this particular test so their data are not included | Mean | Standard Deviation | units on a scale |
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| Epworth Sleepiness Scale | Modified Epworth for children (Melendres et al 2004); 8 questions with each item summed; minimum score 0, maximum score 24. No SD. Higher scores are worse | Epworth sleepiness scale score missing for one participant | Mean | Standard Deviation | units on a scale |
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| Multiple Sleep Latency Test (MSLT) | Mean sleep latency of five 30-min nap attempts. Minimum would be 0 and maximum would be 30 (average of all naps). Shorter times indicate higher sleepiness. | Mean | Standard Deviation | minutes |
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| Quality of Life | Quality of Life is measured by the PedsQL on a scale of 0 to 100, with higher scores meaning better quality of life | Mean | Standard Deviation | units on a scale |
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| Academic Achievement Score | Scores are reported as Standardized scores with a mean of 100 and SD of 15. Minimum value 40; Maximum value 160. Higher scores are better | Mean | Standard Deviation | units on a scale |
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| Fluid Cognition Composite Age Adjusted score | Scores are reported as Standardized scores with a mean of 100 and SD of 15. Minimum value 40; Maximum value 160; SD = 15; higher scores are better | Subject age was too young for this particular test, so their data is not included. | Mean | Standard Deviation | units on a scale |
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| (Apnea-Hypopnea Index (AHI) | Mean | Standard Deviation | events/hour |
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| Sleep Related Breathing Disturbances (SBRD) sub-scale of Pediatric Sleep Questionnaire | The ratio of number of positive responses to the questionnaire divided by the total number of responses. Minimum 0 maximum 1. A ratio of 0.33 or more suggests high risk for sleep-disordered breathing. | Mean | Standard Deviation | Ratio |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Behavioral Index After 6 Months of CPAP or No-CPAP | The sum of the T-scores of The Conners' Parent Rating Scales (CPRS-R:L, ADHD index) and the Child Behavior Checklist (CBCL, Attention Deficit/Hyperactivity Problems) are used to construct the primary study outcome measure Behavioral Index. Behavioral index is a T score (adjusted for age and gender) with a range of "<10" to ">90" - where higher scores mean worse behavior and lower scores mean better behavior, so a negative change score represents an improvement in behavior. T-scores with a mean of 50 and SD of 10 are computed. | Data for two participants in the control group are not available. | Posted | Mean | Standard Deviation | T score | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Secondary | Change in Cognition as Shown by NIH Toolbox Composite Score | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40 and Maximum value 160. Higher scores are better | Lower numbers of participants analyzed are shown here because the tool is not appropriate for younger children | Posted | Mean | Standard Deviation | score on a scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Secondary | Change in Sleepiness as Measured by Epworth Sleepiness Scale | Epworth Sleepiness Scale scores range from 0 to 24 where higher scores mean greater sleepiness. | Data for two participants are not available | Posted | Mean | Standard Deviation | score on a scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Secondary | Change in Sleepiness After AT as Measured by Multiple Sleep Latency Test (MSLT) | Multiple Sleep Latency Test (MSLT) is an objective measure of sleepiness determined by measure of brain waves and other physiological signals over a 30 minute period. This is measured for five 30 minute periods across the day and average latency to sleep for each participant across those times were used to calculate the mean sleep latency. The score is measured in how quickly one would fall asleep, measured in minutes, so a negative number of minutes in the change score means that participants fell asleep more quickly than previously. | Data for one participant are not available | Posted | Mean | Standard Deviation | minutes | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Secondary | Change in Quality of Life as Measured by Peds QL | Peds-QL is a quality of life symptom measurement with a score range of 0 to 100. Higher scores are better quality of life | Data for one participant is not available | Posted | Mean | Standard Deviation | score on a scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Secondary | CPAP Adherence as Measured by Number of Participants Who Used the CPAP Consistently. | CPAP adherence data will be downloaded from CPAP machines. It is defined for this study as using the CPAP machine for at least an average of 4 hours per night during the last 60 days of the assignment. | Posted | Count of Participants | Participants | Starting at 4 months after AT and continuing through 10 months after AT |
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| Other Pre-specified | Change in Cognition as Measured by Fluid Cognition Scores | Scores are reported as standardized scores with a mean of 100 and SD of 15. Minimum value 40, Maximum value 160. Higher scores are better | Lower numbers are shown here as the tool is not appropriate for younger children | Posted | Mean | Standard Deviation | score on a scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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| Other Pre-specified | Change in Cognition After AT as Shown by Academic Achievement | Academic achievement mean score is a standardized score with a mean of 100 and SD 15. Minimum value 40 and Maximum value 160. Higher scores are better | Data from two participants are not available | Posted | Mean | Standard Deviation | units on a scale | assessed as change from baseline to 6 months of CPAP therapy or no-CPAP |
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Adverse events were followed from consent (which could be before surgery or after surgery) until 10 months after surgery equating to six months after assignment.
Based on the adverse event collection structure, it bears noting that some reported AEs may have happened prior to assignment to CPAP or no CPAP use, to participants who ended up reaching baseline visit (4 months after surgery). Since both adherent and non-adherent CPAP participants received CPAP with minimum 1 night of CPAP, these 2 groups were combined for the purposes of AE reporting in order to determine whether any CPAP exposure vs control group (no CPAP) had a different proportion of AE's.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CPAP Treatment Group on CPAP | Children randomized to this arm were assigned and began up to 6 months of CPAP treatment, beginning at approximately 4 months after AT, in addition to standard of care. This arm shows AEs that happened to participants randomized to CPAP but who didn't cross over to the No CPAP group prior to sleep lab. (n=69; original n=71 minus n=2 who crossed over to no-CPAP group). Since both adherent and non-adherent CPAP participants received CPAP and had at minimum one night of CPAP exposure, these two groups were combined for the purposes of AE reporting in order to determine whether any CPAP exposure vs control group (no CPAP) had a different proportion of AE's. | 0 | 69 | 6 | 69 | 59 | 69 |
| EG001 | No CPAP Treatment Group | Children shown in this comparison arm were randomized to NO CPAP or were crossed over to No CPAP prior to any CPAP use or CPAP trial in sleep lab.) (N = 36, original 34 plus two crossed over from those randomized to CPAP) | 0 | 36 | 7 | 36 | 26 | 36 |
| EG002 | Non-randomized Participants | Participants who were consented but withdrew prior to randomization (n = 15) | 0 | 15 | 4 | 15 | 7 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for ashthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Post-operative hospitalization | Surgical and medical procedures | Systematic Assessment | Pre-scheduled hospitalizations or within 48 hours of surgery (prior to randomization in the trial) |
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| ER admission due to panic attack | Psychiatric disorders | Systematic Assessment | This occurred after signing consent but prior to randomization |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic Reaction | Immune system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Asthma Exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Behavior Issues | Social circumstances | Systematic Assessment |
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| Cold Symptoms | General disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Ear Pain | Ear and labyrinth disorders | Systematic Assessment |
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| Enuresis | Renal and urinary disorders | Systematic Assessment |
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| Flu-like Symptoms | General disorders | Systematic Assessment |
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| GI Distress | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| HFMD | Infections and infestations | Systematic Assessment |
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| Life Event or Change | Social circumstances | Systematic Assessment |
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| Molluscum Contagiosum | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pink Eye | Eye disorders | Systematic Assessment |
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| Skin Irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Stomach Flu | Gastrointestinal disorders | Systematic Assessment |
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| Strep Throat | Infections and infestations | Systematic Assessment |
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| Unrelated Accident | Injury, poisoning and procedural complications | Systematic Assessment |
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| Upper Respiratory Infection | Infections and infestations | Systematic Assessment |
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| Voice Alteration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ronald Chervin | University of Michigan | 734-647-9064 | chervin@med.umich.edu |
| Jan 7, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D012891 | Sleep Apnea Syndromes |
| D002653 | Child Behavior Disorders |
| D001289 | Attention Deficit Disorder with Hyperactivity |
| D006970 | Disorders of Excessive Somnolence |
| D000077260 | Sleepiness |
| D001519 | Behavior |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D045422 | Continuous Positive Airway Pressure |
| D035061 | Control Groups |
| ID | Term |
|---|---|
| D011175 | Positive-Pressure Respiration |
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012138 | Respiratory Therapy |
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
| D008722 | Methods |
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