The current study examines longitudinal changes in sleep disturbances and the risks they pose for new-onset health conditions in survivors of childhood cancer. Five-year survivors (N = 1081; median [range] age 50.0 [45.2–55.0] years) and siblings (N = 214; age 49.2 [39.9–51.1] years) from the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI) at two time points (median interval = 17 years). Sex-specific changes of PSQI scores were assessed, adjusting for demographics, using generalized estimating equation. Within survivors, logistic regressions estimated associations between persistent clinically significant sleep disturbances with diagnosis and treatment exposures, and new-onset chronic health conditions. Female siblings reported increases in sleep disturbances (T1 35
Although pediatric hematopoietic stem cell transplantation (HSCT) patients often experience sleep disruptions during hospitalization, no clinical guidelines exist for how to manage their sleep. We sought to learn how clinicians approach inpatient sleep disruptions by surveying 111 pediatric HSCT medical prescribers, nurses, and psychosocial staff from across the United States. Clinicians estimated 58% of inpatients developed sleep issues. Although they rated external factors (e.g., noise) as most impactful, clinicians were most likely to implement patient-level interventions (e.g., melatonin). Research is needed to assess the efficacy of commonly delivered treatments, as well as to develop and implement systems-level changes addressing external sleep barriers.
OBJECTIVE:Pediatric cancer patients are at increased risk for sleep disturbances; however, there are no clinical practice guidelines for treating sleep disturbances in pediatric oncology, resulting in variable approaches to sleep management across clinicians. The current study surveyed clinicians regarding their approaches to assessing and treating sleep. METHODS:A total of 200 pediatric oncology clinicians participated in a REDCap survey about behavioral and medical sleep concerns assessed in their practice and related treatment approaches. RESULTS:Most clinicians (61%) reported assessing sleep when patients or families raised a concern, and 10% reported never assessing sleep. Clinicians rated behavioral difficulties with sleep onset (M = 3.00, SD = 1.08) and insomnia (M = 2.91, SD = 0.99) as the most problematic sleep concerns. Sleep hygiene was the most widely endorsed intervention across almost every sleep concern. Behavioral strategies were used with similar frequency between physicians/APPs compared to other clinicians [ORs = 0.61-1.25]. Pharmacology was used more frequently by physicians/APPs than other clinicians for behavioral sleep concerns [ORs = 0.19-0.36]. CONCLUSIONS:Relying on children and families to report concerns can be a missed opportunity to identify sleep disturbances early. The most endorsed treatment, sleep hygiene, is likely ineffective as a standalone treatment for complex sleep disturbances seen in oncology. It is possible that offering patients these simple but likely ineffective treatments alone may perpetuate long-term sleep disturbances and a lack of confidence in the ability to effectively treat sleep. Further research is needed to determine the most effective treatment approaches for behavioral sleep disturbances, informing clinical practice guidelines for pediatric oncology.
BACKGROUND:Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems. AIMS:Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer. METHODS:This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), health behaviors, mental health, and pain were collected in 2014-2016, and self-reported sleep quality in 2017-2019. Multivariable logistic regression models examined frailty status as a predictor of clinically significant poor sleep. All models were adjusted for age at diagnosis, age at survey, sex, race/ethnicity, smoking, risky/heavy alcohol use, and physical inactivity. Separate models included treatment-related variables, CHC burden (number/severity), and emotional health/pain as co-variates. RESULTS:Frail survivors had 6-fold (95% CI 4.48-7.96) increased odds of future poor sleep quality. Little attenuation of this association was observed when accounting for cancer diagnosis (Odds Ratio [OR] 5.80, 95% CI 4.47-7.52), treatment exposures (OR 5.80, 95% CI 4.43-7.71), or chronic health condition burden (OR 5.12, 95% CI 3.98-6.59), but adjustment for emotional health/pain (OR 2.88, 95% CI 2.18-3.82) attenuated the association appreciably. CONCLUSIONS:Frail childhood cancer survivors have a higher prevalence of clinically significant poor sleep quality. Addressing poor physiologic reserve may impact sleep in frail childhood cancer survivors.
BACKGROUND:Adolescent and young adult survivors of childhood cancer (AYA) are at risk for treatment-related late effects (eg, heart and lung problems) which may be mitigated by physical activity (PA). To design effective, tailored PA interventions for this population, predictors and benefits of PA behavior need to be measured in real-time. PURPOSE:To examine the feasibility and acceptability of ecological momentary assessment (EMA) combined with accelerometry and explore the dynamic associations between PA and real-time physical and psychosocial factors among AYA. METHODS:AYA (N = 20, mean age = 18.9 years) recently off cancer treatment participated in a 2-week intensive monitoring protocol in which they completed up to 4 EMA surveys/day assessing current mood, pain, fatigue, arousal, PA intentions and motivation, and social-environmental context, while PA levels were passively monitored using a wrist-worn ActiGraph GT9X accelerometer. Acceptability was measured via self-report. RESULTS:EMA and accelerometry were feasible and acceptable (≥70% compliance and study endorsement) for AYA. Multilevel models showed that AYA engaged in more PA when they were away from home, with others, in a better mood, less fatigued, more energetic, and more motivated than their own average levels. Further, when AYA engaged in more PA than their usual levels in the hour before completing an EMA survey, they subsequently reported less fatigue, less pain, more energy, and a more positive mood. CONCLUSIONS:EMA and accelerometry are acceptable and feasible among AYA survivors of childhood cancer. This methodology can be utilized for understanding the real-time barriers, facilitators, and benefits of PA behaviors in this at-risk population to design effective, dynamic PA interventions.
Sleep is a neurophysiologic and behavioral state essential for wellness. Pediatric cancer survivors are at elevated risk of developing sleep problems due to cancer and/or treatment-related factors, but their sleep health is understudied. We used unsupervised clustering to identify sleep health profiles in survivors and controls and evaluated differences in emotional function across sleep groups. Long-term survivors (> 5 years from diagnosis) of Hodgkin lymphoma (n=224, mean±SD age=40±9.5) and matched community controls (n=184, age=38±11.4) completed sleep questionnaires. Following the SATED model, sleep health components were derived from PSQI responses indicating Satisfaction, Alertness, Timing, Efficiency, and Duration. Continuous sleep metrics were computed as Euclidean distances of associated PSQI items, and Latent Profile Analysis identified sleep profiles. Parametric bootstrapped likelihood ratio tests estimated the number of profiles and robustness was assessed using Adjusted Rand Index. The health-related quality-of-life (SF36) and Brief Symptom Inventory (BSI-18) evaluated emotional function, and ANOVAs, t-tests, and χ2 assessed group differences. Three sleep profiles were identified: good-sleepers (PSQI=3.6±1.8), average-sleepers (PSQI=6.9±2.9), and poor-sleepers (PSQI=10.2±3.2). Profile distribution was significantly different between survivors and controls (χ2=19.2, p< 0.001) with a larger proportion of survivors in the poor-sleeper profile (33.9%vs15.2%). Average-sleepers had worse Alertness than good-sleepers, with no difference compared to poor-sleepers (F (2,405)=68.2,p< 0.001). Good-sleepers had better Timing than poor-sleepers, with no difference compared to average sleepers (F(2,405)=30.1,p< 0.001). Differences between all three profiles were found in Satisfaction (F(2,405)=85.7,p< 0.001), Efficiency (F(2,405)=110.7,p< 0.001), and PSQI disturbances (F(2,405)=71.4,p< 0.001), but no differences in Duration (F(2,405)=1.4,p=0.237). Considering quality-of-life, survivors have worse bodily pain, general health, and physical and role-physical limitations compared to controls. Poor-sleepers survivors reported worse mental (t(79)=-2.8,p< 0.001) and emotional health (t(78)=-2.5,p< 0.001). No sleep profile evidenced Survivor vs Control differences for depression or anxiety symptoms. Distinctive sleep health profiles were found in pediatric Hodgkin lymphoma survivors and community controls. Survivors reported more pain, poorer general health, and more physical and role-physical limitations, while poor-sleepers exhibited worse mental and emotional health compared to controls. We highlight the importance of understanding the dimensions of sleep health to inform targeted interventions focused on improving overall well-being in pediatric cancer survivors. NCI-NCI-NIH:1R01CA215405,T32CA225590;SRSF-Mentored-Collaboration-Grant(2024)
Optimization of oncolytic viruses for therapeutic applications requires the strategic removal or mutagenesis of virulence genes alongside the insertion of transgenes that enhance viral replication, spread and immunogenicity. However, the complexity of many viral genomes and the labour-intensive nature of methods for the generation and isolation of recombinant viruses have hindered the development of therapeutic oncolytic viruses. Here we report an iterative strategy that exploits the preferential susceptibility of viruses to certain antibiotics to accelerate the engineering of the genomes of oncolytic viruses for the insertion of immunomodulatory cytokine transgenes, and the identification of dispensable genes with regard to replication of the recombinant oncolytic viruses in tumour cells. We applied the strategy by leveraging insertional mutagenesis via the Sleeping Beauty transposon system, combined with long-read nanopore sequencing, to generate libraries of herpes simplex virus type 1 and vaccinia virus, identifying stable transgene insertion sites and gene deletions that enhance the safety and efficacy of the viruses. The preferential susceptibility of oncolytic viruses to certain antibiotics can be exploited to accelerate the engineering of oncolytic viruses expressing transgenes for immunomodulatory cytokines.
Sleep concerns are common during pediatric cancer treatment and can last into survivorship. The current systematic review sought to identify intervention studies that addressed sleep as a primary or secondary outcome during pediatric cancer treatment up to 5 years after completing treatment. Quality assessment was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The review identified 16 studies with a total of 943 participants that tested a wide range of interventions including psycho-educational, stress management techniques, medications, and physical activity. Most studies included tested interventions in small samples. None of the included studies had a high risk of bias for all domains, but all included studies had a high risk of bias for at least two risk domains. Several feasible pilot studies were identified that warrant further research to test efficacy. Implications for future research and clinical practice to manage sleep concerns are discussed.
Background: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. Methods: Childhood cancer survivors (>= 5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. Results: Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). Conclusions: Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.
BACKGROUND:Patients undergoing hematopoietic stem cell transplant (HSCT) experience barriers to quality sleep. Frequent vital sign checks are necessary early posttransplant given risk of complications but can disrupt sleep. This study tested feasibility and acceptability of extending time between checking vitals (EVs) from every 4 to every 6 h to improve sleep.PROCEDURE:HSCT patients ages 8-21 years (N = 50, mean age = 14.06, SD = 3.58) and their caregivers were enrolled 1-2 days prior to transplant, and 40 patients completed the 15-day study (NCT04106089). Patients wore an actigraph to estimate sleep and provided self- and caregiver-report of sleep. Sleep was observed for nights 0 to +4 posttransplant, and patients were then randomized to EVs either Days +5 to +9 or +10 to +14. Patients were assessed daily for medical eligibility to receive EVs; on days patients were eligible, nightshift nurses (N = 79) reported EV acceptability.RESULTS:Of 200 potential nights for EVs (5 nights x 40 patients), patients were eligible for EVs on 126 nights (63% of eligible nights), and patients received EVs on 116 (92%) of eligible nights. Most patients received EVs ≥3 nights (n = 26, 65%, median = 3 nights). Most patients (85%), caregivers (80%), and nurses (84%) reported that patients used the additional 2 h during EVs for sleep, with reporters indicating moderate to high acceptability. There was preliminary evidence of efficacy indicated by caregiver-reported sleep disturbance and actigraphy-estimated improvements in sleep efficiency during EVs.CONCLUSION:Extending time between vitals checks is highly acceptable to patients, caregivers, and nurses, and may offer a feasible approach to improve sleep in pediatric HSCT.
Objectives: The purpose of this explanatory sequential design study was to better understand caregivers' perceptions about and interest in evidencebased early childhood sleep health promotion recommendations. Method: A purposeful sample of mothers of 20 1-5-year-old children (10 children exhibiting optimal sleep and 10 children exhibiting insufficient/ fragmented sleep) attending a preschool serving a low socio-economic (SES) status metropolitan community were invited to participate in qualitative interviews. Data were coded according to a grounded theory approach and themes were identified within the optimal and suboptimal sleeper groups. Results: Mothers reported different approaches to managing electronics by optimal/suboptimal sleeper group, with mothers of optimal sleepers limiting access to electronics more than mothers in the suboptimal sleep group. Other themes of sleep health practices did not differ meaningfully between groups. Conclusions: Maternal perspectives about early childhood sleep health were similar across optimal and suboptimal sleepers on most elements of child sleep health. Managing child sleep was contextually influenced and these results highlight the complexities of how families living in lower SES environments perceive common sleep recommendations. Thus, sleep health education efforts should be tailored to the needs and values of specific families and communities.
Purpose: A cancer diagnosis in young adulthood can negatively impact sleep quality. The present study describes sleep issues in young adults (YAs) and analyzes potential demographic and clinical characteristics related to sleep quality.Methods: Canadian YAs (n = 359) diagnosed with cancer between ages 15-39 participated in the study. Pittsburgh Sleep Quality Index (PSQI) items were examined to identify specific sleep issues that occurred 3+ times per week. Logistic regression was used to examine demographic, clinical, and symptom-related variables associated with poor sleep quality (defined as a PSQI global score >8) and sleep medication use.Results: Participants were predominantly female (87.5%) with an average age of 32 years. Of the sample, 52% had poor sleep quality, 55.5% took >30 min to fall asleep, 32.9% slept <7 h, and 54.6% reported a habitual sleep efficiency of <85%. YAs with poor sleep quality were 5.7 times more likely to report severe distress (p=<.001), as well as 1.8 times more likely to report poorer mental (p = .03) and physical functioning (p = .05). Nearly half (44%) of YAs used sleep medication to help them sleep. YAs who reported severe psychological distress were 2.4 times more likely to use sleeping medication (p = .01), whereas those with a household income & GE;$100,000/year were half as likely to use medication to help with sleep (p = .04).Conclusion: Psychological distress is associated with worse sleep quality and sleep medication use in YA cancer survivors. Sleep quality may be a possible target for future research and intervention to promote long-term function and recovery.
Introduction Triple negative breast cancer (TNBC) is the most aggressive and hard-to-treat subtype of breast cancer, affecting 10-20% of all women diagnosed with breast cancer. Surgery, chemotherapy and hormone/Her2 targeted therapies are the cornerstones of treatment for breast cancer, but women with TNBC do not benefit from these treatments. Although the prognosis is dismal, immunotherapies hold significant promise in TNBC, even in wide spread disease because TNBC is infiltrated with more immune cells. This preclinical study is proposing to optimize an oncolytic virus-infected cell vaccine (ICV) based on a prime-boost vaccination strategy to address this unmet clinical need. Methods We used various classes of immunomodulators to improve the immunogenicity of whole tumor cells in the prime vaccine, followed by their infection with oncolytic Vesicular Stomatitis Virus (VSVd51) to deliver the boost vaccine. For in vivo studies, we compared the efficacy of a homologous prime-boost vaccination regimen to a heterologous strategy by treating 4T1 tumor bearing BALB/c mice and further by conducting re-challenge studies to evaluate immune memory responses in surviving mice. Due to the aggressive nature of 4T1 tumor spread (akin to stage IV TNBC in human patients), we also compared early surgical resection of primary tumors versus later surgical resection combined with vaccination. Results In vitro results demonstrated that immunogenic cell death (ICD) markers and pro-inflammatory cytokines were released at the highest levels following treatment of mouse 4T1 TNBC cells with oxaliplatin chemotherapy and influenza vaccine. These ICD inducers also contributed towards higher dendritic cell recruitment and activation. With the top ICD inducers at hand, we observed that treatment of TNBC-bearing mice with the influenza virus-modified prime vaccine followed by VSVd51 infected boost vaccine resulted in the best survival. Furthermore, higher frequencies of both effector and central memory T cells along with a complete absence of recurrent tumors were observed in re-challenged mice. Importantly, early surgical resection combined with prime-boost vaccination led to improved overall survival in mice. Conclusion Taken together, this novel cancer vaccination strategy following early surgical resection could be a promising therapeutic avenue for TNBC patients.
BackgroundCaregivers and adolescents and young adult (AYA) cancer survivors may be at greater psychosocial risk from the COVID-19 pandemic than healthy peers due to complex and traumatic medical histories. This study describes COVID-19-related event exposures, impact, and distress among a large sample of caregivers and AYA cancer survivors and the relationship of these variables to demographic and cancer characteristics. ProcedureFrom May 2020 to December 2021, 422 caregivers and 531 AYA survivors completed the COVID-19 Exposures and Family Impact Survey (CEFIS) and CEFIS-AYA, respectively. Total COVID-19-related exposures, average COVID-19-related impact, and COVID-19-related distress were calculated. Conventional content analysis was used to analyze free-text responses about the negative and positive effects of COVID-19. ResultsCaregivers and AYA reported an average of 7.4-7.8 COVID-19 exposures to pandemic-related events and a slightly negative impact of COVID-19 across psychosocial domains, with some positive impacts reported. COVID-19-related distress was moderate and clinically meaningful (4.9-5.2/10) for AYA and caregivers. Racial and ethnically minoritized AYA and caregivers reported higher COVID-19-related distress than non-Hispanic white caregivers. For AYA, distress was also higher among female, college-age (18-22 years), and long-term survivors compared with males, younger AYA, White and those recently off treatment. CEFIS outcomes remained relatively stable over time. ConclusionsCOVID-19 had a significant and consistent negative impact on caregivers and AYA survivors. Racial and ethnically minoritized families and female, college-age, and long-term AYA survivors may require additional psychosocial support. Assessing for COVID-19 impact and distress is important in pediatric oncology to evaluate adjustment and plan targeted interventions.
Abstract Introduction Sleep problems following treatment for childhood cancer may persist into adulthood. Because some sleep problems increase with age, it is important to understand whether cancer elevates this risk and assess associations with co-morbidities that frequently develop in long-term childhood cancer survivors. The current study compares sleep in long-term survivors to sibling controls. Methods Childhood cancer survivors (≥5 years from diagnosis; n=12,340; 51.5% female; mean [SD] age=39.4 [9.6] years; years since diagnosis=30.9 [7.9]; age at diagnosis=8.5 [5.8]) and siblings (n=2395; 57.1% female; age=44.6 [10.5]) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Binary sleep behaviors (Total Score >5, Short Sleep Duration [< 6 hours], Frequent Snoring [>3 times/week], Frequent Sleep Medication Use [≥3 times/week]) were compared between survivors and siblings using a multivariable generalized estimating equation with Poisson error to account for intra-family correlations, adjusting for age, sex, race, and BMI. Poisson regression models evaluated treatment and chronic health conditions (CHCs) as predictors of PSQI Total Score among survivors with the same adjustment variables. Results Survivors were more likely to report Short Sleep Duration (12.0% vs 10.6%; adjusted prevalence ratio [aPR] 1.18, 95% confidence interval [CI] 1.04-1.34), elevated PSQI Total Score (45.1% vs 40.0%; aPR 1.17, 95%CI 1.11-1.23), Frequent Snoring (18.0% vs 17.4%; aPR 1.11, 95%CI 1.01-1.23), and Frequent Sleep Medication Use (13.2% vs 11.5%; aPR 1.28, 95% CI 1.14-1.45) compared to siblings. Among survivors, elevated PSQI Total Score was associated with female sex (aPR 1.29, 95%CI 1.21-1.37) and BMI (overweight: aPR 1.13, 95%CI 1.06-1.22; obese: aPR 1.32, 95%CI 1.23-1.42), while age at diagnosis and cancer treatment exposures (i.e., chemotherapy/radiation) were not significantly associated. Survivors with 2+ CHCs had increased prevalence of elevated PSQI Total Score (aPR 1.39, 95%CI 1.28-1.50) relative to survivors without CHCs. Conclusion Childhood cancer survivors exhibit elevated risk for poor sleep quality, short sleep, and snoring relative to siblings well into middle age. These sleep problems are driven by demographics and current chronic health conditions rather than prior treatment exposures. Elevated use of sleep-promoting medications suggests interest in managing sleep difficulties and an opportunity for future behavioral sleep intervention trials. Support (if any) NCI 5U24CA055727-26 (PI: Armstrong)
Brain tumours are among the most common cancer diagnoses in paediatrics. Children with brain tumours are at risk of developing sleep problems because of direct and indirect effects of the tumour and its treatment, in addition to psychosocial and environmental factors. Sleep has an important role in physical and psychological wellbeing, and sleep problems are associated with many adverse outcomes. In this Review, we describe the state of the evidence regarding sleep in people with paediatric brain tumours, prevalence and types of sleep problems, risk factors, and effectiveness of interventions. Evidence shows that sleep problems, particularly excessive daytime sleepiness, are common in people with paediatric brain tumours, with high BMI emerging as a consistent predictor of sleep disruption. Further intervention studies are needed, and clinical evaluation of sleep is warranted for people with paediatric brain tumours.
OBJECTIVE:Previous studies of sleep patterns, as well as rates and correlates of perceived problems in early childhood, indicate variation by neighborhood-level socioeconomic indicators. The purpose of this study was to examine variation in (1) sleep patterns, behaviors, and problems by family-based socioeconomic indicators (income-to-needs ratio and caregiver education level) and (2) sociodemographic and sleep correlates of a caregiver-endorsed child sleep problem across and within socioeconomic indicator groups in a diverse sample. METHODS:Two hundred eighty-three caregiver-child dyads (ages 1-5 years) completed the Brief Child Sleep Questionnaire. Family-level socioeconomic indicators included income-to-needs ratio and caregiver educational level. RESULTS:Sleep patterns varied based on income-to-needs ratio, with children living in poverty experiencing the longest sleep onset latencies and night awakening durations and shortest nighttime sleep durations. Rates of an endorsed child sleep problem were similar across income-to-needs groups. Although sleep patterns did not vary by caregiver education level, caregivers with an education beyond high school were more likely to endorse a child sleep problem; later bedtimes, more frequent night awakenings, and greater bedtime difficulties were the strongest correlates of a perceived sleep problem in this subgroup. No specific correlates of a child sleep problem emerged for those with a high school education or less. CONCLUSION:Sleep patterns may be more robustly linked to family income-to-needs ratio, whereas perceptions of a child sleep problem may be more linked to caregiver education level. Clinicians should consider expanding sleep screening questions to include specific sleep outcomes to effectively assess child sleep and guide intervention.