Impact of atopic dermatitis treatment on child and parent sleep, daytime functioning, and quality of life

Journal Pre-proof Impact of Atopic Dermatitis Treatment on Child/Parent Sleep, Daytime Functioning, and Quality of Life Lisa J. Meltzer, PhD, Kassie D. Flewelling, MA, Stephanie Jump, BS, Elizabeth Gyorkos, PA-C, Michael White, BS, Pia J. Hauk, MD PII:

S1081-1206(19)31531-5

DOI:

https://doi.org/10.1016/j.anai.2019.12.024

Reference:

ANAI 3116

To appear in:

Annals of Allergy, Asthma and Immunology

Received Date: 30 October 2019 Revised Date:

23 December 2019

Accepted Date: 27 December 2019

Please cite this article as: Meltzer LJ, Flewelling KD, Jump S, Gyorkos E, White M, Hauk PJ, Impact of Atopic Dermatitis Treatment on Child/Parent Sleep, Daytime Functioning, and Quality of Life, Annals of Allergy, Asthma and Immunology (2020), doi: https://doi.org/10.1016/j.anai.2019.12.024. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Impact of Atopic Dermatitis Treatment on Child/Parent Sleep, Daytime Functioning, and Quality of Life Lisa J. Meltzer, PhD1; Kassie D. Flewelling, MA2; Stephanie Jump, BS1; Elizabeth Gyorkos, PA-C1; Michael White, BS1; Pia J. Hauk, MD1 1

2

National Jewish Health

University of Colorado Denver

Author Contributions: LJM was responsible for the conception and design of the study, as well as the data analysis and interpretation. KDF was responsible for data acquisition, data analysis, and interpretation. SG, EG, and MW were responsible for data acquisition, and PJH was responsible for the conception and design of the study, as well as data interpretation. LJM and KDF drafted the manuscript and all other authors critically reviewed it for important intellectual content. All authors have given their final approval of the version to be published and all authors agree to be accountable for all aspects of the work related to its accuracy or integrity. Funding: This work was supported by the National Eczema Association. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Corresponding author: Lisa J. Meltzer, PhD National Jewish Health 1400 Jackson St. G311 Denver, CO 80206 Phone: (303) 398-1837 Email: [email protected]

HEALING ECZEMA AND IMPROVING SLEEP 1

Introduction

2

Atopic dermatitis (AD) impacts up to 20% of children worldwide (1;2). Children with

3

AD experience physical discomfort, poorer quality of life (3-5), increased behavior problems

4

(6;7), higher frequency of attention-deficit/hyperactivity disorder (ADHD) (8-11) and higher

5

healthcare utilization (12). Parents of children with AD report decreased quality of life (13-16),

6

negative impact on the family (14;17), increased depression and anxiety (16), and increased

7

work absenteeism (18;19).

8

1

Subjective sleep disturbances are common among children with AD (20-22) and their

9

parents (16;23). However, most previous studies have utilized a single sleep question and relied

10

on parent-report. A small number of studies have used actigraphy, an objective estimate of sleep-

11

wake patterns, finding children with AD have poorer sleep efficiency (proportion of time asleep

12

divided by time trying to sleep), longer sleep onset latency (time to fall asleep at bedtime), and

13

more fragmented sleep (20;24;25). Across studies, sleep disturbances increase with AD severity

14

(7;24;26). No studies have included actigraphy to assess parent sleep duration and quality.

15

Sleep disturbances significantly impact child daytime functioning, including behavior, as

16

well as social, emotional, and cognitive functioning (27-30). In adults, chronic sleep deprivation

17

negatively impacts mood, fatigue, and performance (31-35), with reports of increased medical

18

errors by health care providers following overnight and extended shifts (36;37). As parents of

19

children with AD regularly experience insufficient sleep, they also likely experience subsequent

20

negative daytime functioning.

21

Only one study examined sleep as the primary outcome variable following the use of

22

melatonin to improve sleep in children with AD (38), with results showing greater improvements

23

in SCORAD index (SCORing Atopic Dermatitis) (39), actigraphic sleep onset latency, and

HEALING ECZEMA AND IMPROVING SLEEP

2

24

subjective sleep quality. However, neither parent sleep nor child and parent daytime functioning

25

were considered. The current study addresses gaps in the literature by longitudinally evaluating

26

the benefits of a multidisciplinary treatment program on objective sleep, subjective sleep, and

27

daytime functioning for children with AD and their parents. We hypothesized: 1) objective sleep

28

duration and sleep efficiency would increase in children and parents one-month post-treatment;

29

2) subjective sleep quality and daytime sleepiness would improve in children and parents

30

immediately following AD treatment, with improvements maintained one- and three-months

31

post-treatment; and 3) daytime functioning, quality of life (QoL), and child behavior would

32

improve following AD treatment, with improvements maintained one- and three-months post-

33

treatment.

34 35

Methods This study was approved by the National Jewish Health Institutional Review Board. All

36

applicable ethical standards were followed in conducting the study.

37

Participants

38

Families scheduled for a two-week intensive, multi-disciplinary day treatment program

39

for children with chronic allergic diseases were recruited. Details about the program’s treatment

40

approach are described elsewhere (40). In brief, children with a history of chronic AD who failed

41

previous treatments receive outpatient treatment including wet wrap therapy, evaluations/testing

42

with multi-disciplinary providers (e.g., allergy, immunology, pulmonary, behavioral health), and

43

education. Clinical coordinators identified interested parents/caregivers during pre-registration.

44

The study team sent an invitation letter and called interested families, screening for eligibility. In

45

families with more than one primary caregiver, both parents/caregivers were invited to

46

participate.

HEALING ECZEMA AND IMPROVING SLEEP 47

Inclusion criteria: (a) child age 0.5 to 17.5 years with AD admitted to the pediatric day

48

program; and (b) primary caregiver(s). Exclusion criteria: (a) presence of another significant

49

chronic illness (except related allergic diseases including asthma, allergic rhinitis, food

50

allergies); (b) parent-reported diagnosed sleep disorder in child or parent; (c) parent-reported

51

professional diagnoses of psychiatric or developmental disorder known to disrupt sleep (e.g.,

52

autism, bipolar disease) in child or parent; (d) parent-reported history of neurologic illness or

53

injury in child or parent; and (e) parent night shift work. Eligible participants completed an

54

online consent through REDCap (Research Electronic Database Capture). Children >8 years

55

completed their own online assent form.

56

Procedures

57

Data were collected at four times: (1) Baseline – one week prior to admission/at

58

admission; (2) Post-Treatment – day 13 or 14 (prior to discharge); (3) One-Month Post – one

59

month after discharge; and (4) Three-Months Post – three months after discharge.

60

3

Approximately 10 days prior to admission, participants were mailed actigraphs to wear

61

for the seven nights prior to admission. Devices were collected at admission. Actigraphs were

62

resent to families approximately three weeks after discharge, with reminder calls provided when

63

it was time to start and stop wearing the device. Families were provided a pre-paid envelope to

64

return the devices after seven nights of data collection. Subjective measures of sleep quality and

65

functional outcomes (questionnaires) were completed by parents of all participants and by

66

children >8 years at all four time points. Please see Figure 1 for study outline. Participants

67

received small valued gift cards following completion of each assessment period.

68

Measures

69

Actigraphy. Children and parents wore a Motionlogger Sleep Watch (Ambulatory-

HEALING ECZEMA AND IMPROVING SLEEP 70

Monitoring, Inc., Ardsley, NY) on the non-dominant wrist (or ankle if under the age of three

71

years) for seven nights at Baseline and One-Month Post. For children, devices were used from

72

dinner time to breakfast time, allowing for nocturnal sleep recording, while adults wore devices

73

continuously (removing only during times of potential damage like bathing). Scoring was

74

completed with event marker, light sensor, and sleep diary data. Study outcomes included total

75

sleep duration (number of minutes of sleep between reported bedtime and wake time) and sleep

76

efficiency (total sleep time/time in bed, expressed as a percent). An increase of at least 20

77

minutes in sleep duration and/or 5% in sleep efficiency are considered clinically meaningful

78

(41).

4

79

Daily Sleep Diary. Parents and children (>8 years) completed a 9-item daily sleep diary,

80

sent via email through REDCap, that queried bedtime, rise time, and device removal. These data

81

were used to facilitate accurate scoring of actigraphy.

82

PROMIS Sleep Disturbance and Sleep-Related Impairment. The Patient-Reported

83

Outcomes Measurement Information System (PROMIS) has both adult and pediatric Sleep

84

Disturbance (PROMIS-SD) and Sleep-Related Impairment (PROMIS-SRI) short-forms (8-items)

85

(42;43). PROMIS-SD assesses difficulties with sleep onset, sleep continuity, and sleep quality;

86

PROMIS-SRI measures daytime sleepiness, difficulty waking, and the impact of sleepiness on

87

daytime functioning. Both scales use a seven day recall period and generate T-scores based on

88

large general population samples (mean=50, SD=10). Higher scores indicate greater sleep

89

disturbances/impairment, with both the adult and pediatric versions shown to be reliable, precise,

90

and valid (42-44). At all four assessments, parents completed the self-report adult forms, and the

91

pediatric parent-proxy forms for children >5 years. Children >8 years completed the self-report

92

pediatric forms.

HEALING ECZEMA AND IMPROVING SLEEP 93

5

Brief Infant Sleep Questionnaire - Revised (BISQ-R). The BISQ-R is a reliable and

94

valid parent-report questionnaire that queries sleep patterns and parental perceptions of sleep in

95

infants and toddlers (45-48). Three items from the BISQ-R were administered to parents of

96

children <4 years to assess sleep quality. Parents were instructed to think about their child’s sleep

97

during the past seven nights, and the BISQ-R was completed at all four assessments.

98 99

PROMIS Daytime Functioning Outcome Measures. Three 8-item PROMIS measures were used to capture symptoms of depression, anxiety, and cognitive function. Using a 7-day

100

recall period, higher scores represent more symptoms. All three measures provide T-scores based

101

on large general population samples (mean=50, SD=10), and have been shown to be reliable,

102

valid, and precise across pediatric populations (49). At all four assessments, parents completed

103

the self-report adult forms, and the pediatric parent-proxy forms for children >5 years. Children

104

>8 years completed the self-report pediatric forms.

105

Quality of Life. Parents completed the Dermatitis Family Impact Questionnaire (DFI), a

106

10-item measure of how the child’s AD impacts the family’s quality of life over the previous

107

seven days (15). Total scores provide categorical distinctions of the impact of AD on quality of

108

life (11 to 20 – very large impact, 6 to 10 – moderate impact, 2 to 5 – small impact) with a 4-

109

point change considered a minimal clinically important difference (MCID).

110

Children completed the Children’s Dermatology Life Quality Index (CDLQI), a 10-item

111

measure of the impact of AD on a child’s health-related quality of life and daily activities over

112

the previous seven days (50). Similar to the DFI, categories identify the impact of AD on quality

113

of life (13 to 18 – very large impact, 7 to 12 – moderate impact, 2 to 6 – small impact).

114 115

Child Behavior. The Conners 3 ADHD Index (Conners 3AI) is a 10-item screener for symptoms of ADHD over the past month (51). Children >8 years completed a self-report version

HEALING ECZEMA AND IMPROVING SLEEP 116

and parents of children >5 years completed a parent-proxy version. The Conners uses a

117

standardized T score (mean=50, SD=10). Higher scores represent more ADHD symptoms, with

118

scores >65 considered clinically significant. With a one-month recall period, the Conners 3AI

119

was not administered at Post-Treatment.

120

6

Disease Severity. The Atopic Dermatitis Quickscore (ADQ) (52) provided a parent-

121

report of child disease severity across study time points. The ADQ assesses percentage of body

122

surface involved, intensity of representative area, and pruritus across seven body parts. At

123

Baseline, parents were taught to use the ADQ by a clinical team member. Higher scores indicate

124

greater disease severity.

125

Data Analysis

126

Descriptive statistics were conducted to examine sample demographics, with results

127

presented as mean+SD. Mixed-effects analysis of variance (ANOVA) models were used to test

128

differences in outcome variables over time. This approach accounts for both within and between

129

participant variance. All models specified a random effect of participant ID. Separate models

130

were run for the dependent variables (objective sleep, subjective sleep, daytime functioning,

131

disease severity), with fully saturated models (all main and interaction effects) for group (child,

132

mother, father) and time (Baseline, Post-Treatment, One-Month Post, Three-Months Post).

133

Interpretation of mixed-effects ANOVA starts with the interaction between group and time to see

134

if the outcome changed over time differently for each group. Then the main effect of group

135

(differences between child, mother and father) and time (across the study) are examined

136

separately. Because sleep duration is known to change across development, child age was

137

entered as a covariate for all models. Post-hoc analyses with least significant differences were

138

utilized to further evaluate significant interactions and main effects. With the exception of

HEALING ECZEMA AND IMPROVING SLEEP 139

objective sleep and quality of life, increased/decreased scores are standardized (mean=50,

140

SD=10). Due to the small sample size, only frequencies for the BISQ-R items are reported.

141 142 143

7

Results Participant Characteristics Fifty-eight families were invited to participate in the study; however, 14 were ineligible

144

(i.e., no current eczema, parent worked night shift, comorbid medical/psychiatric disorders,

145

unable to reach prior to program entry) and one declined to participate (stating no direct benefit),

146

thus 44 families provided informed consent/assent. Of these, 14 did not attend the treatment

147

program (e.g., insurance reasons, scheduling conflicts) and one was removed from the study

148

because they left the treatment program early against medical advice. Thus 29 children (17 boys,

149

12 girls, ages 9 months to 15.5 years, 6.3+3.8 years), and their parents (29 mothers, 21 fathers)

150

who participated in the treatment program between June and December 2017 were enrolled. The

151

majority of children were White (72.4%; Native American=10.3%; mixed race=10.3%;

152

Asian=3.4%; unknown=3.4%), with 17.2% Hispanic. Baseline clinician-rated SCORAD index

153

identified AD severity as mild (13.8%), moderate (31.0%), or severe (55.2%). Discharge

154

SCORAD index (14.2+9.4) was significantly lower than admission SCORAD index (62.9+21.9),

155

t(10)=10.74, p<0.001. All participants received topical medications in addition to wet wrap

156

therapy; no participants were on a systemic treatment (e.g., duplimab).

157

Repeated-measures ANOVA found a significant change on the ADQ total score across

158

time, F(3,27)=34.51, p<0.001, with scores significantly higher at Baseline (42.9+11.7) compared

159

to Post-Treatment (14.6+9.8), One-Month Post (15.7+7.6), and Three-Months Post (19.1+7.9).

160

Objective Sleep Outcomes

161

For sleep duration, the group by time interaction was not statistically significant;

HEALING ECZEMA AND IMPROVING SLEEP 162

however, child sleep duration increased by 60 minutes between Baseline and One-Month Post

163

(Table 1). There was a significant main effect for time, with sleep duration increasing (28

164

minutes) from Baseline to One-Month Post for all participants, and a significant main effect for

165

group, with children sleeping more than mothers and fathers.

166

For sleep efficiency, a significant group by time interaction found a large and clinically-

167

significant increase in average child sleep efficiency (9.7%), while changes in sleep efficiency

168

were more modest for mothers (2.3%) and fathers (2.6%) (Table 1).

169

Subjective Sleep Outcomes

170

8

For PROMIS-SD, the group by time interaction was not statistically significant (Table 2);

171

however, children had a greater and clinically-significant decrease in Sleep Disturbances from

172

Baseline to Three-Months Post (decrease 11.6) compared to mothers (decrease 7.1) or fathers

173

(decrease 6.4). A significant main effect for time showed PROMIS-SD scores were significantly

174

lower for all participants at all three post-treatment assessments (vs. Baseline), and a significant

175

main effect for group showed child Sleep Disturbance was greater than both mothers and fathers.

176

For PROMIS-SRI, the group by time interaction was not statistically significant (Table

177

2); however, the change in sleep-related impairment from Baseline to One-Month Post was

178

greater for children (decrease 7.9) and mothers (decrease 7.6) than fathers (decrease 5.8).

179

Children had a further decrease at Three-Months Post (3.7), while improvements in Sleep-

180

Related Impairments were maintained for mothers and fathers. There was a significant time main

181

effect, with PROMIS-SRI significantly lower at all three post-treatment assessments (vs.

182

Baseline). There was no main effect for group.

183 184

Sleep quality in young children (BISQ-R, Table 3) improved somewhat at PostTreatment, with greater improvements noted at One- and Three-Months Post. Night waking

HEALING ECZEMA AND IMPROVING SLEEP

9

185

frequency improved from Baseline (only 40.0% of children waking 0-1 time/night) to One-

186

Month Post (83.3% waking 0-1 time/night), and maintained at Three-Months Post (72.8%

187

waking 0-1 time/night). A similar improvement was seen in children sleeping well following AD

188

treatment (Baseline: 50%, One-Month Post: 100%, Three-Months Post: 90%). Finally, more

189

children were described as happy upon waking in the morning following AD treatment

190

(Baseline: 40%, One-Month Post: 91.7%, Three-Months Post: 81.8%).

191

Daytime Functioning

192

Table 4 shows mixed model results for daytime functioning outcomes. For anxiety, there

193

was a significant group by time interaction, with greater decreases in anxiety symptoms from

194

Baseline to One-Month Post in children (decrease 10.6) than mothers (decrease 4.5) or fathers

195

(decrease 3.7). Improvements in anxiety were maintained at Three-Months Post for all groups. A

196

significant main effect for time showed that anxiety symptoms were lower at all three post-

197

treatment times (vs. Baseline), while a significant main effect for group showed mothers

198

experiencing higher levels of anxiety symptoms than children.

199

A significant group by time interaction was found for depressive symptoms, with greater

200

decreases in depressive symptoms from Baseline to One-Month Post in children (decrease 10.1)

201

than mothers (decrease 2.8) or fathers (decrease 3.7). Improvements in depressive symptoms

202

were maintained at Three-Months Post for children and fathers; however, mothers experienced

203

an increase in depressive symptoms (increase 1.8). A significant main effect of time found lower

204

depressive symptoms at all three post-treatment times (vs. Baseline). There was no significant

205

group main effect.

206 207

No statistically significant group by time interaction was found for cognitive functioning; however, mothers and fathers reported increased cognitive functioning at One-Month Post

HEALING ECZEMA AND IMPROVING SLEEP

10

208

compared to Baseline (mothers increase 4.1, fathers increase 5.9), that was maintained at Three-

209

Months Post, while no change was reported for children across time points. A significant main

210

effect for time showed cognitive functioning improved from Baseline to Post-Treatment, with

211

improvements maintained at One-and Three-Months Post. There was no group main effect.

212

Quality of Life

213

When comparing QoL scores between mothers and fathers, no significant group by time

214

interaction or group main effect emerged (Table 4). However, a significant main effect of time

215

was observed, with QoL improving from Baseline to Post-Treatment (decrease 4.4), with further

216

improvements at One-Month Post (additional decrease 5.0) that were maintained at Three-

217

Months Post. For children, although the time main effect was not statistically significant, it is

218

notable that QoL significantly improved from Baseline to Post-Treatment (decrease 6.6), with

219

further improvements reported at One-Month Post (additional decrease 3.1). At Three-Months

220

Post child QoL was slightly higher (2.1 increase).

221

Child Behavior

222

There was no significant time main effect for child ADHD symptoms (Table 4); however,

223

ADHD symptoms improved from Baseline to One-Month Post (decrease 11.9), with slightly

224

higher symptoms at Three-Months Post (2.1 increase, but still significantly lower than Baseline).

225

Discussion

226

This study is one of the first to examine objective and subjective sleep in children and

227

their parents as the primary outcome following intensive multi-disciplinary treatment for chronic

228

pediatric AD. Treatment efficacy was demonstrated with significant improvements in the

229

SCORAD index from admission to discharge. A parallel improvement on the parent-

230

administered ADQ was also observed, with results maintained for three months after program

HEALING ECZEMA AND IMPROVING SLEEP 231 232

11

completion. Objective sleep duration one month after discharge increased by almost 30 minutes on

233

average across all participants, and notably by 60 minutes for children. A 20-minute increase in

234

sleep duration is considered clinically meaningful for insomnia treatment (41), with a 30-minute

235

increase resulting in child cognitive and behavioral improvements (53;54). Further, objective

236

sleep efficiency for children significantly increased (9.3%), with a 5% increase considered

237

clinically meaningful (41). Parental sleep efficiency changes were more modest, due to an

238

already restricted parental sleep opportunity (without enough time to sleep at night, sleep

239

efficiency is higher). However, the objective improvements in sleep quantity and quality in

240

parents remains noteworthy.

241

At Baseline children’s sleep disturbances/impairments were similar to or greater than

242

children in a sleep clinic or children with autism (55), further highlighting the significant sleep

243

disturbances and impaired daytime functioning in children with chronic AD. However,

244

subjective sleep outcomes improved after AD treatment, in particular for children, with results

245

maintained for 3 months after discharge. For young children, there was a significant

246

improvement in night wakings, sleep quality, and mood upon waking. Parental subjective sleep

247

outcomes also improved, although to a lesser degree. The decrease of ~0.5 standard deviation in

248

parent sleep is consistent with PROMIS measured sleep outcomes following PAP therapy for

249

obstructive sleep apnea in adults (56). Together the subjective changes in sleep for children and

250

their parents are consistent with the objective sleep findings and suggest the importance of

251

adequate treatment of the child’s AD in order to improve child and parent sleep.

252 253

Daytime functioning also improved for children and their parents. While within the normal range, child anxiety and depression improved by ~1 standard deviation one month after

HEALING ECZEMA AND IMPROVING SLEEP

12

254

discharge, highlighting the negative impact of poorly controlled AD on child well-being. Further,

255

improvements were seen in quality of life for children, mothers, and fathers, with scores moving

256

from “very significant impact” to “small/moderate impact” one month after discharge.

257

Improvements were maintained for parents at three-months after discharge, with only a slight

258

increase in negative impact reported by children. Finally, although not statistically significant,

259

child behavior scores not only improved by >1 standard deviation, ADHD symptoms dropped

260

from the clinically significant range to the normal range.

261

Future research should address study limitations. First, although this study provides a

262

longitudinal examination of outcomes related to the treatment of AD, results cannot be causally

263

interpreted. Future studies should include a control group to compare changes across time.

264

Second, we did not collect three-month post-treatment actigraphy data. It is important for future

265

studies to also include longer follow-up, as well as to examine the impact of improved sleep and

266

daytime functioning on healthcare utilization. Third, loss to follow-up and an overall small

267

sample size precluded our ability to examine differences by child sex, race or ethnicity, which

268

may impact the generalizability of results. Fourth, we did not assess treatment adherence post-

269

discharge, thus it is unknown how that may have impacted the 1-month and 3-month study

270

findings. Finally, as with any subjective measurement, reporter bias may have influenced

271

participant responses on questionnaires.

272

Despite these limitations, study findings highlight the importance for clinicians on

273

recognizing the significant impact of AD on sleep and daytime functioning of both children and

274

their parents. As insufficient or poor-quality sleep is associated with both mood and behavior,

275

when pediatric AD patients or parents are tearful or irritable, or parents report increased child

276

behavior issues during an AD flare, this may be due in part to disrupted sleep. In summary, study

HEALING ECZEMA AND IMPROVING SLEEP

13

277

results suggest the successful management of child AD improves sleep and daytime functioning

278

in children and parents, with benefits maintained over time.

Acknowledgements The authors thank the participants and their families for their time and effort, as well as Sara Hammerbeck, clinical coordinator, and Elizabeth Esterl, DNP, for their assistance with referring families to the study. This study was funded by the National Eczema Association.

1 Reference List (1) Spergel JM. Epidemiology of atopic dermatitis and atopic march in children. Immunol Allergy Clin North Am. 2010;30(3):269-80. (2) Hanifin JM, Reed ML. A population-based survey of eczema prevalence in the United States. Dermatitis. 2007;18(2):82-91. (3) Chamlin SL, Chren MM. Quality-of-life outcomes and measurement in childhood atopic dermatitis. Immunol Allergy Clin North Am. 2010;30(3):281-8. (4) Hon KL, Leung TF, Wong KY, Chow CM, Chuh A, Ng PC. Does age or gender influence quality of life in children with atopic dermatitis? Clin Exp Dermatol. 2008;33(6):705-9. (5) Alvarenga TM, Caldeira AP. Quality of life in pediatric patients with atopic dermatitis. J Pediatr (Rio J). 2009;85(5):415-20. (6) Strom MA, Fishbein AB, Paller AS, Silverberg JI. Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults. Br J Dermatol. 2016. (7) Chang HY, Seo JH, Kim HY, Kwon JW, Kim BJ, Kim HB, et al. Allergic diseases in preschoolers are associated with psychological and behavioural problems. Allergy Asthma Immunol Res. 2013;5(5):315-21. (8) Camfferman D, Kennedy JD, Gold M, Martin AJ, Winwood P, Lushington K. Eczema, sleep, and behavior in children. J Clin Sleep Med. 2010;6(6):581-8. (9) Lin YT, Chen YC, Gau SS, Yeh TH, Fan HY, Hwang YY, et al. Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children. Pediatr Res. 2016. (10) Schmitt J, Chen CM, Apfelbacher C, Romanos M, Lehmann I, Herbarth O, et al. Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus. Allergy. 2011;66(3):404-11. (11) Genuneit J, Braig S, Brandt S, Wabitsch M, Florath I, Brenner H, et al. Infant atopic eczema and subsequent attention-deficit/hyperactivity disorder--a prospective birth cohort study. Pediatr Allergy Immunol. 2014;25(1):51-6. (12) Silverberg JI, Simpson EL. Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 2013;24(5):476-86. (13) Gelmetti C, Boralevi F, Seite S, Grimalt R, Humbert P, Luger T, et al. Quality of life of parents living with a child suffering from atopic dermatitis before and after a 3-month treatment with an emollient. Pediatr Dermatol. 2012;29(6):714-8.

2 (14) Ricci G, Bendandi B, Bellini F, Patrizi A, Masi M. Atopic dermatitis: quality of life of young Italian children and their families and correlation with severity score. Pediatr Allergy Immunol. 2007;18(3):245-9. (15) Lawson V, Lewis-Jones MS, Finlay AY, Reid P, Owens RG. The family impact of childhood atopic dermatitis: The Dermatitis Family Impact questionnaire. Brit J Dermatol. 1998;138(1):107-13. (16) Moore K, David TJ, Murray CS, Child F, Arkwright PD. Effect of childhood eczema and asthma on parental sleep and well-being: A prospective comparative study. Brit J Dermatol. 2006;154(3):514-8. (17) Beattie PE, Lewis-Jones MS. An audit of the impact of a consultation with a paediatric dermatology team on quality of life in infants with atopic eczema and their families: further validation of the Infants' Dermatitis Quality of Life Index and Dermatitis Family Impact score. Br J Dermatol. 2006;155(6):1249-55. (18) Mancini AJ, Kaulback K, Chamlin SL. The socioeconomic impact of atopic dermatitis in the United States: a systematic review. Pediatr Dermatol. 2008;25(1):1-6. (19) Kemp AS. Atopic eczema: its social and financial costs. J Paediatr Child Health. 1999;35(3):229-31. (20) Chang YS, Chou YT, Lee JH, Lee PL, Dai YS, Sun C, et al. Atopic dermatitis, melatonin, and sleep disturbance. Pediatrics. 2014;134(2):e397-e405. (21) Dahl RE, Bernhisel-Broadbent J, Scanlon-Holdford S, Sampson HA, Lupo M. Sleep disturbances in children with atopic dermatitis. Arch Pediatr Adolesc Med. 1995;149(8):856-60. (22) Hon KL, Leung TF, Wong KY, Chow CM, Chuh A, Ng PC. Does age or gender influence quality of life in children with atopic dermatitis? Clin Exp Dermatol. 2008;33(6):705-9. (23) Reid P, Lewis-Jones MS. Sleep difficulties and their management in preschoolers with atopic eczema. Clin Exp Dermatol. 1995;20(1):38-41. (24) Hon KL, Lam MC, Leung TF, Kam WY, Lee KC, Li MC, et al. Nocturnal wrist movements are correlated with objective clinical scores and plasma chemokine levels in children with atopic dermatitis. Br J Dermatol. 2006;154(4):629-35. (25) Bringhurst C, Waterston K, Schofield O, Benjamin K, Rees JL. Measurement of itch using actigraphy in pediatric and adult populations. J Am Acad Dermatol. 2004;51(6):893-8. (26) Chamlin SL, Mattson CL, Frieden IJ, Williams ML, Mancini AJ, Cella D, et al. The price of pruritus: Sleep disturbance and cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med. 2005;159(8):745-50.

3 (27) Beebe DW. Cognitive, behavioral, and functional consequences of inadequate sleep in children and adolescents. Pediatr Clin North Am. 2011;58(3):649-65. (28) Bates JE, Viken RJ, Alexander DB, Beyers J, Stockton L. Sleep and adjustment in preschool children: sleep diary reports by mothers relate to behavior reports by teachers. Child Dev. 2002;73(1):62-74. (29) Komada Y, Abe T, Okajima I, Asaoka S, Matsuura N, Usui A, et al. Short sleep duration and irregular bedtime are associated with increased behavioral problems among Japanese preschool-age children. Tohoku J Exp Med. 2011;224(2):127-36. (30) Vaughn BE, Elmore-Staton L, Shin N, El-Sheikh M. Sleep as a support for social competence, peer relations, and cognitive functioning in preschool children. Behav Sleep Med. 2015;13(2):92-106. (31) Dinges DF, Rogers NL, Baynard MD. Chronic sleep deprivation. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Elsevier Saunders; 2005. p. 67-76. (32) Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: Dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003;26(2):117-26. (33) Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, Redmond DP, et al. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: A sleep dose-response study. J Sleep Res. 2003;12(1):1-12. (34) Harrison Y, Horne JA. Sleep loss impairs short and novel language tasks having a prefrontal focus. J Sleep Res. 1998;7(2):95-100. (35) Pilcher JJ, Huffcutt AI. Effect of sleep deprivation on performance: A meta-analysis. Sleep. 1996;19(4):318-26. (36) Anderson C, Sullivan JP, Flynn-Evans EE, Cade BE, Czeisler CA, Lockley SW. Deterioration of neurobehavioral performance in resident physicians during repeated exposure to extended duration work shifts. Sleep. 2012;35(8):1137-46. (37) Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E, Katz JT, et al. Effects of reducing interns' work hours on serious medical errors in intensive care units. N Engl J Med. 2004;351(18):1838-48. (38) Chang YS, Lin MH, Lee JH, Lee PL, Dai YS, Chu KH, et al. Melatonin supplementation for children with atopic dermatitis and sleep disturbance: A randomized clinical trial. JAMA Pediatr. 2016;170(1):35-42.

4 (39) Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007;157(4):645-8. (40) Reference blinded for peer review (41) Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307-49. (42) Buysse DJ, Yu L, Moul DE, Germain A, Stover A, Dodds NE, et al. Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments. Sleep. 2010;33(6):781-92. (43) Forrest CB, Meltzer LJ, Marcus CL, De La Motte A, Kratchman A, Buysse DJ, et al. Development and validation of the PROMIS Pediatric Sleep Disturbance and SleepRelated Impairment item banks. Sleep. 2018; doi: 10.1093/sleep/zsy054. [Epub ahead of print]. (44) Bevans KB, Meltzer LJ, De La Motte A, Kratchman A, Viel D, Forrest CB. Qualitative development and content validation of the PROMIS Pediatric Sleep Health items. Behav Sleep Med. 2019;17(5):657-671. (45) Mindell JA, Gould R, Tikotzky L, Leichman ES, Walters RM. Norm-referenced scoring system for the Brief Infant Sleep Questionnaire - Revised (BISQ-R). Sleep Med. 2019. (46) Sadeh A. A brief screening questionnaire for infant sleep problems: Validation and findings for an Internet sample. Pediatrics. 2004;113(6):e570-e577. (47) Mindell JA, Du Mond CE, Sadeh A, Telofski LS, Kulkarni N, Gunn E. Efficacy of an internet-based intervention for infant and toddler sleep disturbances. Sleep. 2011;34(4):451-8. (48) Mindell JA, Du Mond CE, Sadeh A, Telofski LS, Kulkarni N, Gunn E. Long-term efficacy of an internet-based intervention for infant and toddler sleep disturbances: one year follow-up. J Clin Sleep Med. 2011;7(5):507-11. (49) DeWalt DA, Gross HE, Gipson DS, Selewski DT, Dewitt EM, Dampier CD, et al. PROMIS((R)) pediatric self-report scales distinguish subgroups of children within and across six common pediatric chronic health conditions. Qual Life Res. 2015;24(9):2195208. (50) Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index (CDLQI): initial validation and practical use. Br J Dermatol. 1995;132(6):942-9. (51) Conners CK. Conners 3rd edition. 3rd ed. Toronto, Ontario, Canada: Mulit-Health Systems; 2008.

5 (52) Carel K, Bratton DL, Miyazawa N, Gyorkos E, Kelsay K, Bender B, et al. The Atopic Dermatitis Quickscore (ADQ): validation of a new parent-administered atopic dermatitis scoring tool. Ann Allergy Asthma Immunol. 2008;101(5):500-7. (53) Sadeh A, Gruber R, Raviv A. The effects of sleep restriction and extension on school-age children: What a difference an hour makes. Child Dev. 2003;74(2):444-55. (54) Gruber R, Cassoff J, Frenette S, Wiebe S, Carrier J. Impact of sleep extension and restriction on children's emotional lability and impulsivity. Pediatrics. 2012;130(5):e1155-e1161. (55) Meltzer, L. J., Forrest, C. B., de la Motte, A., & Bevans, K. B. (in press). Clinical validity of the PROMIS pediatric sleep measures across populations of children with chronic illnesses and neurodevelopmental disorders. Journal of Pediatric Psychology. (56) Donovan L, Yu L, Bertisch SM, Buysse D, Rueschman M, Patel SR. Responsiveness of patient reported outcomes to obstructive sleep apnea treatment with continuous positive airway pressure therapy. Presented at the 2019 World Sleep Society Congress, Vancouver, BC, Canada.

1 Table 1. Mixed Model Results for Objective Sleep Outcomes (Actigraphy) Baseline

1-Month Post

Duration (minutes) Post-hoc comparisons Child

434.83 (14.13)

494.61 (10.37)

Mother

408.95 (14.41)

433.60 (10.45)

Father

368.58 (16.39)

390.96 (12.89)

Efficiency (percent) Post-hoc comparisons Child

0.72 (0.02)

0.81 (0.01)

Mother

0.85 (0.02)

0.87 (0.01)

Group F

Time F

Group*Time F

14.47***

17.52**

2.21

F
B<1M

10.45***

26.49***

C
B<1M

7.14**

Father 0.82 (0.02) 0.84 (0.02) Data presented as Mean (+SE) ***p < .001; **p < .01; *p < .05 Note. Group*Time examines whether changes over study time (Baseline to 1-Month Post) differs by group. The main effect for Group examines whether there are differences (regardless of time) between child (C), mother (M) and father (F). The main effect for time examines whether there are differences (regardless of group) between Baseline (B) and 1-Month Post (1M).

2 Table 2. Mixed Model Results for Subjective Sleep Outcomes (PROMIS) Baseline

Post-Treatment

1-Month Post

3-Months Post

Sleep Disturbance Post-hoc comparisons Child

65.08 (1.94)

56.32 (2.10)

57.16 (1.70)

53.51 (1.94)

Mother

56.02 (1.45)

51.89 (1.55)

48.45 (1.24)

48.92 (1.42)

54.66 (1.70)

45.16 (2.20)

48.90 (1.53)

48.27 (1.66)

Father Sleep-Related Impairment Post-hoc comparisons

Group F

Time F

12.46***

22.36***

F, M
B>PT, 1M, 3M

0.29

13.36***

Group* Time F 1.82

1.17

B>PT, 1M, 3M

Child

56.71 (2.32)

50.12 (2.52)

51.19 (2.35)

47.89 (2.25)

Mother

57.68 (1.70)

53.16 (1.89)

49.78 (1.73)

50.93 (1.66)

Father 54.91 (2.00) 49.29 (2.59) 52.31 (2.12) 49.48 (1.94) Data presented as Mean (+SE) ***p < .001; **p < .01; *p < .05 Note. Group*Time examines whether changes over study time (Baseline to 1-Month Post) differs by group. The main effect for Group examines whether there are differences (regardless of time) between child (C), mother (M) and father (F). The main effect for time examines whether there are differences (regardless of group) between Baseline (B), Post-Treatment (PT), 1-Month Post (1M), and 3Months Post (3M). Higher scores indicate poorer sleep.

3 Table 3. Descriptive Statistics [Percent (n)] for Sleep Outcomes in Young Children (<4 Years; BISQ-R) Baseline

PostTreatment

1-Month Post

3-Months Post

40.0 (4)

50.0 (6)

83.3 (10)

72.8 (8)

Twice/night

30.0 (3)

25.0 (3)

8.3 (1)

27.3 (3)

>3 times/night

30.0 (3)

25.0 (3)

8.3 (1)

50.0 (5)

66.7 (8)

100.0 (12)

50.0 (5)

33.3 (4)

40.0 (4)

75.0 (9)

91.7 (11)

81.8 (9)

Neutral

30.0 (3)

8.3 (1)

8.3 (1)

18.2 (2)

Fussy

30.0 (3)

16.7 (2)

Night waking frequency 0-1 time/night

How well child sleeps at night Very well/fairly well/well Very poor/fairly poor/poor Child’s mood upon waking in morning Happy

90.0 (10) 9.1 (1)

4 Table 4. Mixed Model Results for Measures of Daytime Functioning, Quality of Life and Child Behavior (PROMIS, DFI, Conners 3AI) Baseline

Post-Treatment

1-Month Post

3-Months Post

Group F

Time F

Group* Time F 2.96*

3.22* 14.85*** Anxiety Post-hoc comparisons CPT>1M, 3M Child 52.29 (2.47) 47.99 (2.58) 39.30 (2.68) 41.74 (2.68) Mother 54.63 (1.87) 52.66 (1.95) 50.51 (1.99) 50.15 (2.68) Father 50.01 (2.20) 46.57 (2.55) 47.76 (2.41) 46.31 (2.33) 0.54 12.47*** 2.54* Depression Post-hoc comparisons B>PT, 1M, 3M Child 51.22 (2.15) 45.40 (2.01) 41.17 (1.97) 43.75 (2.39) Mother 48.58 (1.62) 45.70 (1.52) 45.82 (1.46) 47.62 (1.76) Father 48.20 (1.90) 42.38 (1.99) 44.52 (1.77) 44.61 (2.06) 1.05 4.72** 1.69 Cognitive Function Post-hoc comparisons BPT>1M, 3M Mother 16.10 (1.58) 12.52 (1.61) 6.23 (1.19) 6.84 (1.29) Father 14.86 (1.86) 9.66 (2.19) 6.00 (1.44) 6.82 (1.52) Child 14.30 (5.65) 7.67 (5.68) 4.57 (5.10) 6.67 (5.07) --2.81 --Post-hoc comparisons ADHD Symptoms Child 67.00 (5.67) --55.13 (4.29) 57.24 (5.03) --2.23 --Post-hoc comparisons Data presented as Mean (+SE), ***p < .001; **p < .01; *p < .05. Group*Time examines whether changes over study time (Baseline to 1Month Post) differs by group. The main effect for Group examines whether there are differences (regardless of time) between child (C), mother (M) and father (F). The main effect for time examines whether there are differences (regardless of group) between Baseline (B), Post-Treatment (PT), 1-Month Post (1M), and 3-Months Post (3M). For Anxiety, Depression, and Quality of Life higher scores indicate poorer functioning. For Cognitive Function higher scores indicate better functioning.

Figure 1. Study Overview

3-4 Weeks Prior to Baseline Participant consent (n=44 families)

Excluded (n=15 families) Did not attend program (n=14) Left program early (n=1) Actigraphy sent 10 days prior to admission (baseline)

1 Week Prior to Baseline 7 nights of actigraphy (Child = 27, Mother = 26, Father = 20)

Baseline Subjective assessment (Child=29, Mother=29, Father=21)

Treatment at Medical Center

Post-Treatment Subjective assessment (Child=29, Mother=29, Father=21)

Actigraphy sent 3 weeks after discharge (post-treatment)

One-Month Post Treatment 7 nights of actigraphy Subjective assessment (Child=25, Mother=25, Father=16)

3-Months Post Treatment Subjective assessment (Child=25, Mother=25, Father=18)