Sex bias in pain management decisions.

In the pursuit of mental and physical health, effective pain management stands as a cornerstone. Here, we examine a potential sex bias in pain management. Leveraging insights from psychological research showing that females' pain is stereotypically judged as less intense than males' pain, we hypothesize that there may be tangible differences in pain management decisions based on patients' sex. Our investigation spans emergency department (ED) datasets from two countries, including discharge notes of patients arriving with pain complaints (N = 21,851). Across these datasets, a consistent sex disparity emerges. Female patients are less likely to be prescribed pain-relief medications compared to males, and this disparity persists even after adjusting for patients' reported pain scores and numerous patient, physician, and ED variables. This disparity extends across medical practitioners, with both male and female physicians prescribing less pain-relief medications to females than to males. Additional analyses reveal that female patients' pain scores are 10% less likely to be recorded by nurses, and female patients spend an additional 30 min in the ED compared to male patients. A controlled experiment employing clinical vignettes reinforces our hypothesis, showing that nurses (N = 109) judge pain of female patients to be less intense than that of males. We argue that the findings reflect an undertreatment of female patients' pain. We discuss the troubling societal and medical implications of females' pain being overlooked and call for policy interventions to ensure equal pain treatment.

Physicians prescribe fewer analgesics during night shifts than day shifts.

Adequate pain management is one of the biggest challenges of the modern healthcare system. Physician perception of patient subjective pain, which is crucial to pain management, is susceptible to a host of potential biases. Here we explore the timing of physicians' work as a previously unrecognized source of systematic bias in pain management. We hypothesized that during night shifts, sleep deprivation, fatigue, and stress would reduce physicians' empathy for others' pain, leading to underprescription of analgesics for patient pain relief. In study 1, 67 resident physicians, either following a night shift or not, performed empathy for pain assessment tasks and simulated patient scenarios in laboratory conditions. As predicted, following a night shift, physicians showed reduced empathy for pain. In study 2, we explored this phenomenon in medical decisions in the field. We analyzed three emergency department datasets from Israel and the United States that included discharge notes of patients arriving with pain complaints during 2013 to 2020 (n = 13,482). Across all datasets, physicians were less likely to prescribe an analgesic during night shifts (compared to daytime shifts) and prescribed fewer analgesics than generally recommended by the World Health Organization. This effect remained significant after adjusting for patient, physician, type of complaint, and emergency department characteristics. Underprescription for pain during night shifts was particularly prominent for opioids. We conclude that night shift work is an important and previously unrecognized source of bias in pain management, likely stemming from impaired perception of pain. We consider the implications for hospitals and other organizations employing night shifts.

Modelling of primary ciliary dyskinesia using patient-derived airway organoids.

Patient-derived human organoids can be used to model a variety of diseases. Recently, we described conditions for long-term expansion of human airway organoids (AOs) directly from healthy individuals and patients. Here, we first optimize differentiation of AOs towards ciliated cells. After differentiation of the AOs towards ciliated cells, these can be studied for weeks. When returned to expansion conditions, the organoids readily resume their growth. We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways. Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations. More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure. Additionally, using genetic editing tools, we show that a patient-specific mutation can be repaired. This study demonstrates the utility of organoid technology for investigating hereditary airway diseases such as PCD.

Neurological and neurodevelopmental symptoms in children with familial Mediterranean fever and their siblings.

Familial Mediterranean fever is a common autoinflammatory disease characterized by periodic attacks of fever and serositis. There are few reports describing neurological symptoms in patients with FMF. The aim of this study was to systematically assess the neurologic and developmental involvement in pediatric patients with FMF. Between the years 2016 and 2019, parents of children with FMF were asked to complete a questionnaire regarding the presence of neurological and developmental symptoms in their children with and without FMF. Demographic data, clinical characteristics, and disease course of FMF patients were collected from the medical charts. Neurodevelopmental manifestations were compared between the children with FMF and their siblings. A total of 205 children were enrolled (11.6 ± 4.7 years of age): 111 children with FMF and 94 healthy siblings in the control group. Neurological morbidity was frequently reported in children with FMF: 44 (40%) had recurrent headaches, 31 (28%) ADHD symptoms, 27 (24%) learning disabilities, and 10 (9%) febrile convulsions. Headaches and febrile convulsions were significantly more prevalent in children with FMF as compared to their siblings (ps < 0.05). ADHD and learning disabilities were associated with poor adherence to colchicine treatment.Conslusions: The present study found an increased prevalence of ADHD, learning disabilities, headaches, and febrile seizures in children with FMF. The findings underscore the importance of addressing the neurodevelopmental domain in children with FMF. In addition, detection and treatment of ADHD and learning disabilities could improve adherence with therapy and control of the underlying disease. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and arthritis. • Some previous case reports also described rare neurological manifestations in children with FMF. What is New: • The study found an increased prevalence of headaches, febrile seizures, ADHD, and learning disabilities, in children with FMF. • The findings underscore the importance of addressing the neurological domain in this population, which could potentially improve adherence with therapy and control of the underlying disease.

Chronic Intermittent Hypoxia during Sleep Causes Browning of Interscapular Adipose Tissue Accompanied by Local Insulin Resistance in Mice.

Obstructive sleep apnea (OSA) is a highly prevalent condition, characterized by intermittent hypoxia (IH), sleep disruption, and altered autonomic nervous system function. OSA has been independently associated with dyslipidemia, insulin resistance, and metabolic syndrome. Brown adipose tissue (BAT) has been suggested as a modulator of systemic glucose tolerance through adaptive thermogenesis. Reductions in BAT mass have been associated with obesity and metabolic syndrome. No studies have systematically characterized the effects of chronic IH on BAT. Thus, we aimed to delineate IH effects on BAT and concomitant metabolic changes. C57BL/6J 8-week-old male mice were randomly assigned to IH during sleep (alternating 90 s cycles of 6.5% FIO2 followed by 21% FIO2) or normoxia (room air, RA) for 10 weeks. Mice were subjected to glucose tolerance testing and 18F-FDG PET-MRI towards the end of the exposures followed by BAT tissues analyses for morphological and global transcriptomic changes. Animals exposed to IH were glucose intolerant despite lower total body weight and adiposity. BAT tissues in IH-exposed mice demonstrated characteristic changes associated with "browning"-smaller lipids, increased vascularity, and a trend towards higher protein levels of UCP1. Conversely, mitochondrial DNA content and protein levels of respiratory chain complex III were reduced. Pro-inflammatory macrophages were more abundant in IH-exposed BAT. Transcriptomic analysis revealed increases in fatty acid oxidation and oxidative stress pathways in IH-exposed BAT, along with a reduction in pathways related to myogenesis, hypoxia, and IL-4 anti-inflammatory response. Functionally, IH-exposed BAT demonstrated reduced absorption of glucose on PET scans and reduced phosphorylation of AKT in response to insulin. Current studies provide initial evidence for the presence of a maladaptive response of interscapular BAT in response to chronic IH mimicking OSA, resulting in a paradoxical divergence, namely, BAT browning but tissue-specific and systemic insulin resistance. We postulate that oxidative stress, mitochondrial dysfunction, and inflammation may underlie these dichotomous outcomes in BAT.

Acute and chronic sleep deprivation in residents: Cognition and stress biomarkers.

OBJECTIVES: Insufficient sleep affects circadian hormonal profiles and inflammatory markers and may modulate attention, executive functioning and decision-making. Medical professionals and specifically resident physicians, who are involved in long-term nightshift schedules during their post-graduate training, are prone to acute and chronic sleep deprivation and disruption, putting them at risk for making medical errors. The aim of the study was to evaluate the impact of chronic and acute-on-chronic sleep deprivation and disruption among residents on selected physiological and cognitive measures. METHODS: Thirty-three medical and surgical residents were evaluated twice - at baseline and after a 26-hour shift. Eighteen young attending physicians who did not engage in nightshift schedules served as controls and were evaluated once. Measures included morning cortisol and high-sensitivity C-reactive protein (hs-CRP), computerised tests of attention and behaviour, the Behaviour Rating Inventory of Executive Function, a risk-taking questionnaire and the Pittsburgh Sleep Quality Index. RESULTS: Residents, but not attendings, reported chronic sleep disruption and deprivation. Residents at baseline exhibited reduced morning cortisol levels and elevated hs-CRP levels, compared to attendings. Residents at baseline had impaired global executive function compared to attendings. A nightshift with acute sleep deprivation further reduced residents' executive function. Residents at baseline and after a nightshift demonstrated increased impulsivity and slower processing time than attendings. Residents and attendings did not differ in risk-taking tendencies which were assessed in a separate cohort. CONCLUSIONS: In a real-life setting, resident physicians exhibit increased low-grade systemic inflammation (hs-CRP) and impaired HPA-axis function. Their chronic sleep curtailment is associated with greater impulsivity, slower cognitive processing, and impaired executive function. Future research is warranted to understand how improving working schedule by increasing sleep duration may minimise the short-term and potential long-term risks to physicians in training.

Understanding the pathophysiological mechanisms of cardiometabolic complications in obstructive sleep apnoea: towards personalised treatment approaches.

In January 2019, a European Respiratory Society research seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide, which occur frequently in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, and to discuss pitfalls of current models and the design of future collaborative studies. In addition, we debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches.

[APNEA OF PREMATURITY - PATHOPHYSIOLOGY, TREATMENT & PROGNOSIS].

INTRODUCTION: Apnea of prematurity affects the majority of infants born before 34 weeks of complete gestation. Significant recurrent apnea of prematurity is associated with both short and long term complications and is a risk factor for increased mortality and neurodevelopmental disability. The current review discusses the recent advances in the understanding of the pathophysiology of apnea of prematurity, as well as the clinical questions relevant to physicians and staff treating infants with apnea of prematurity. Finally, we discuss monitoring and discharge decisions, and present recommendations following discharge from the neonatal intensive care unit.

Pyogenic sacroiliitis in children: don't forget the very young.

Pyogenic sacroiliitis (PS) is rare with less than 100 pediatric cases reported in the medical literature. To better characterize PS in the pediatric population, we investigated a series of children presenting with PS. Retrospective data analysis was done at an academic tertiary center between the years of 2000 and 2017. All hospitalized children ≤ 16 years of age with PS were evaluated. Of the 894 children hospitalized with osteoarticular infections, 18 were diagnosed with PS (2%) and are included in the review. Two clinically distinct groups were identified. PS in infants (n = 13, 72.2%, mean age 1.1 years) had an indolent course and a faster recovery without any bacterial source identified. In contrast, the group of older children (n = 5, 27.8%, mean age 11.6 years) had a more complicated course and a higher rate of identified bacterial infections.Conclusion: We describe an under-recognized entity of PS in infants with a mild clinical course and fast recovery that differ from the "classical" septic sacroiliitis. Infants with PS did not suffer from invasive complications, and pathogen characteristics of older children were not identified. Infants with fever, irritability, decreased range of motion in the pelvic area, and pain during diapering should alert the clinician to this diagnosis. What is Known: • Pediatric pyogenic sacroiliitis is an extremely rare condition usually caused by Staphylococcus aureus with highest incidence in adolescents. • The diagnosis of PS is challenging due to its rarity and difficulty in assessing the sacroiliac joint. What is New: • We describe an under-recognized entity of PS in infants with a mild clinical course, without invasive complications and with fast recovery that differ from "classical" septic sacroiliitis. • Infants with fever, irritability, decreased range of motion in the pelvic area and pain during diapering should raise clinical suspicion of this diagnosis.

Activation of the Integrated Stress Response and Metabolic Dysfunction in a Murine Model of Sleep Apnea.

Intermittent hypoxia (IH) induces activation of the integrated stress response (ISR), but its role in IH-induced visceral white adipose tissue (vWAT) insulin resistance is unknown. CHOP is activated by chronic ISR, whereas GADD34 dephosphorylates the subunit of translation initiation factor 2 (eIF2α), leading to termination of the ISR. We hypothesized that CHOP/Gadd34 null mice would not manifest evidence of insulin resistance after IH exposures. Eight-week-old CHOP/GADD34-/- (double mutant [DM]) and wild-type (WT) littermates were randomly assigned to IH or room air (RA) exposures for 6 weeks. Glucose and insulin tolerance tests were performed, and regulatory T cells (Tregs) and macrophages in vWAT were assessed. Phosphorylated eIF2α:total eIF2α, ATF4, XBP1 expression, and insulin-induced pAKT/AKT expression changes were examined in vWATs. Single GADD34-/- and PERK+/- mice were also evaluated. Body weight and vWAT mass were reduced in DM and WT mice after IH. M1/M2 macrophages and inflammatory macrophages (Ly-6chigh) were significantly increased in WT vWAT but remained unchanged in DM mice. Tregs were significantly decreased in WT vWAT but not in DM mice. Systemic insulin and glucose tolerance tests revealed insulin resistance in IH-WT but not in IH-DM mice. Similarly, decreased pAKT/AKT responses to exogenous insulin emerged in IH-WT compared with RA-WT mice, whereas no significant differences emerged in IH-DM compared with DM-RA. Chronic ISR activation appears to contribute to the insulin resistance and vWAT inflammation that characteristically emerge after long-term IH exposures in a murine model of obstructive sleep apnea.

Visceral White Adipose Tissue after Chronic Intermittent and Sustained Hypoxia in Mice.

Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1α-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1α transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1α gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH > IH > RA; P < 0.001), with vWAT in IH manifesting vascular rarefaction and increased proinflammatory macrophages. HIF-1α ChIP-sequencing showed markedly increased binding sites in SH-exposed vWAT both at 6 hours and at 6 weeks compared with IH, the latter also showing decreased vascular endothelial growth factor, endothelial nitric oxide synthase, P2RX5, and PAT2 expression, and insulin resistance (IH > > > SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1α activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1α transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.

Intermittent hypoxia causes NOX2-dependent remodeling of atrial connexins.

BACKGROUND: Obstructive sleep apnea has been linked to the development of heart disease and arrhythmias, including atrial fibrillation. Since altered conduction through gap junction channels can contribute to the pathogenesis of such arrhythmias, we examined the abundance and distributions of the major cardiac gap junction proteins, connexin40 (Cx40) and connexin43 (Cx43) in mice treated with sleep fragmentation or intermittent hypoxia (IH) as animal models of the components of obstructive sleep apnea. RESULTS: Wild type C57BL/6 mice or mice lacking NADPH 2 (NOX2) oxidase activity (gp91phox(-/Y)) were exposed to room air or to SF or IH for 6 weeks. Then, the mice were sacrificed, and atria and ventricles were immediately dissected. The abundances of Cx40 or Cx43 in atria and ventricles were unaffected by SF. In contrast, immunoblots showed that the abundance of atrial Cx40 and Cx43 and ventricular Cx43 were reduced in mice exposed to IH. qRT-PCR demonstrated significant reductions of atrial Cx40 and Cx43 mRNAs. Immunofluorescence microscopy revealed that the abundance and size of gap junctions containing Cx40 or Cx43 were reduced in atria by IH treatment of mice. However, no changes of connexin abundance or gap junction size/abundance were observed in IH-treated NOX2-null mice. CONCLUSIONS: These results demonstrate that intermittent hypoxia (but not sleep fragmentation) causes reductions and remodeling of atrial Cx40 and Cx43. These alterations may contribute to the substrate for atrial fibrillation that develops in response to obstructive sleep apnea. Moreover, these connexin changes are likely generated in response to reactive oxygen species generated by NOX2.

Inflammatory markers and obstructive sleep apnea in obese children: the NANOS study.

INTRODUCTION: Obesity and obstructive sleep apnea syndrome (OSA) are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. AIM: To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG) variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4-15 years) were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. RESULTS: 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI) of 3 events/hour total sleep time (TST). BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P < 0.01), while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P < 0.001). CONCLUSION: IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.

Advances in Sleep-Disordered Breathing in Children.

Pediatric sleep-disordered breathing disorders are a group of common conditions, from habitual snoring to obstructive sleep apnea (OSA) syndrome, affecting a significant proportion of children. The present article summarizes the current knowledge on diagnosis and treatment of pediatric OSA focusing on therapeutic and surgical advancements in the field in recent years. Advancements in OSA such as biomarkers, improving continuous pressure therapy adherence, novel pharmacotherapies, and advanced surgeries are discussed.

The association of obstructive sleep apnea and behavioral insomnia in children ages 10 and under.

STUDY OBJECTIVES: Behavioral insomnia of childhood (BIC) and obstructive sleep apnea (OSA) are highly prevalent conditions affecting 10%-20% and 1%-5% of children, respectively. Studies in adults and adolescents have suggested that comorbid insomnia and OSA may have distinct clinical characteristics. The association between the two conditions in the pediatric population has not been thoroughly investigated. This study aimed to examine the association between BIC and OSA in young children. METHODS: Children, 6 months to 10 years old, referred to a sleep specialist and polysomnography at the Hadassah Medical Center between 2018 and 2021 were included in this retrospective analysis. We excluded children with chromosomal and craniofacial abnormalities, posttonsillectomy, or neurological impairment. BIC diagnosis was extracted from the electronic health records in accordance with the International Classification of Sleep Disorders, third edition criteria. OSA was diagnosed by polysomnography (apnea-hypopnea index > 2 events/h). RESULTS: Of 312 children (age 4.42 ± 2.42 years), 126 (40.4%) were non-OSA non-BIC, 125 (40.1%) OSA non-BIC, 34 (10.9%) BIC non-OSA, and 27 (8.7%) comorbid insomnia and OSA. OSA and non-OSA children had a similar prevalence of BIC. Children in the comorbid insomnia and OSA group were significantly younger (2.22 ± 1.21 years). Younger age at polysomnography, premature birth, and increased periodic leg movements on polysomnography were independently associated with OSA in a multivariable analysis. Lower body mass index, regardless of OSA, was associated with BIC. CONCLUSIONS: Current findings do not support an association between behavioral insomnia of childhood and obstructive sleep apnea in children. Healthcare providers should consider each of these sleep disorders in children presenting with sleep difficulties since each has distinct diagnostic and therapeutic options. CITATION: Yelov L, Reiter J, Meira E Cruz M, Gileles-Hillel A. The association of obstructive sleep apnea and behavioral insomnia in children ages 10 and under. J Clin Sleep Med. 2024;20(2):245-251.

Comprehensive pulmonary function analysis identifies predominant obstructive phenotype in former premature infants around one year of age.

BACKGROUND: Preterm infants suffer from significant respiratory morbidity during the first years of life, but the underlying lung pathophysiology is not fully understood. This study aimed to comprehensively characterize the pulmonary functions of preterm infants using full infant pulmonary function testing (iPFT). METHODS: Between 2008 and 2019, we recruited 150 infants (Mage 10.5 ± 6 months) of them 104 preterm infants (median gestational age [GA] = 34 weeks (28-36), n = 23 with bronchopulmonary disease [BPD]) and 46 controls born at term. We compared full iPFT parameters of preterm infants to a control group of term infants. Subanalysis included a comparison of preterm infants by BPD status and GA. RESULTS: Preterm infants had impaired flow parameters, reduced compliance, and air trapping, compared to term infants. Only 15% (n = 14) of the preterm group had normal iPFT, compared to 69% (n = 31) of the term group. The majority of the impaired iPFT in preterm infants were obstructive and 72% (n = 69) had no response to bronchodilators. Reduced maximal flow at the functional residual capacity point (V'maxFRC) was associated with low birth weight and GA. There were no major differences between preterm infants with or without BPD. CONCLUSIONS: Preterm infants in the first year of life, demonstrated a high prevalence of obstructive iPFT unresponsive to bronchodilators. BPD status did not add to the degree of pulmonary impairment. These data reveal an airway-predominant pathology of the modern-era prematurity-associated lung disease. Pulmonary function screening tests at an early age may be of value in determining the presence and severity of lung disease in the preterm population. V'maxFRC may provide a good assessment of pulmonary impairment in preterm infants.

Changes in ventilation modes in the last decade and their impact on the prevalence of bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Less invasive forms of ventilation have evolved aiming to decrease bronchopulmonary dysplasia (BPD) morbidity. It is unclear whether changes in ventilation practices have been associated with improvements in respiratory outcomes. OBJECTIVE: To examine the changes in ventilation modes in preterm neonates between two periods during the last decade and their impact on BPD prevalence. METHODS: A retrospective chart review of very low birth weight infants and those born at less than 32 weeks gestation hospitalized during two periods: the years 2012-2013 and 2018-2019. The primary outcome was the prevalence of BPD. Study variables included the mode and duration of ventilation, duration of oxygen need, and perinatal clinical parameters. RESULTS: Four hundred eighty-one infants were enrolled. Between the two study periods, a significant increase was observed in invasive (33%-47%, p = 0.002), and noninvasive ventilation rates (44%-72%, p < 0.001). The average duration of noninvasive ventilation increased significantly (from 9.24 to 14.08 days, p = 0.016). The total duration of respiratory support remained unchanged. The overall prevalence of moderate and severe BPD at 36 weeks corrected age remained approximately 40% in preterm infants born at less than 28 weeks gestation. CONCLUSION: The increasing use of non-invasive ventilation was not accompanied by a reduction in the use of invasive ventilation, nor by a reduced prevalence of BPD. The high prevalence of BPD remains a significant problem in extreme prematurity. Other interventions, in addition to less aggressive ventilation, need to be explored.

Changes in Sleep in Children and Adults with Cystic Fibrosis and Primary Ciliary Dyskinesia over Time and after CFTR Modulator Therapy.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are associated with sleep disturbances affecting quality of life (QOL) in both children and adults. However, little is known about the progression of these complaints over time, and the effect of CFTR modulator (CFTRm) therapies. Participants completed sleep quality (SDSC, PSQI) and quality of life questionnaires (PedQL, QOL-BE) as well as the Epworth sleepiness scale (ESS) at baseline and after 4 years. Medical records were reviewed for clinical data and correlations were sought between sleep, QOL, and clinical parameters. A total of 67 patients (33 pediatric), 37 pancreatic insufficient CF (CF-PI), 15 pancreatic sufficient CF (CF-PS), and 15 PCD patients, completed the study. In adults, global sleep quality decreased from 85.8% (76.2-90.5) to 80.9% (71.4-85.7); (p = 0.009). Analysis by disease cohort showed a significant deterioration only in the CF-PS group. In adults off CFTRm, sleep quality decreased from 85.7% (78.6-88.2) to 80.9% (71.4-87.3); (p = 0.021) and from 85.8% (76.2-92.9) to 76.2% (71.4-85.8); (p = 0.078) in people on CFTRm. Changes in sleep quality and changes in QOL over time were strongly associated with each other. In conclusion sleep quality deteriorates over time, correlates with QOL, and is driven primarily by adults and CF-PS patients. CFTRm has a possible effect on sleep initiation; however, results are mixed, and further long-term studies are required.

Sleep disorders in children with celiac disease: a prospective study.

STUDY OBJECTIVES: Celiac disease (CD), an immune-mediated enteropathy, has a clinical spectrum that is remarkably wide and includes neuropsychiatric manifestations. While studies of adults have shown sleep disturbances, there is limited data in children. Our objectives were to assess the association between sleep disturbances and CD in children, and the effect of a gluten-free diet. METHODS: Parents of children 3-12 years old referred for endoscopy completed the Sleep Disturbance Scale for Children and modified Epworth Sleepiness Scale. Children with CD were compared with healthy controls and children with abdominal pain but no definitive findings on investigation. Parents of children with CD and abdominal pain were contacted after 6 months for follow-up. RESULTS: We enrolled 101 patients, mean age 6.5 (2.8), 51% female, 38 with CD, 18 abdominal pain, and 45 healthy. Sleep Disturbance Scale for Children scores were 37.4 (8.7), 41.3 (11.3), and 45.4 (13.7) in healthy controls, CD, and abdominal pain, respectively (P = .024). There was a significant difference in the disorders of arousal domain (P = .044). There were no significant differences on the modified Epworth Sleepiness Scale. A trend toward improvement in Sleep Disturbance Scale for Children scores was seen in children with CD presenting with abdominal pain after 6 months on a gluten-free diet (P = .07). CONCLUSIONS: In this first prospective study of sleep disturbances in children with CD, we show high rates of disturbed sleep compared with healthy children. Sleep disturbances did not improve on a gluten-free diet and may be driven by abdominal pain. CITATION: Reiter J, Abuelhija H, Slae M, et al. Sleep disorders in children with celiac disease: a prospective study. J Clin Sleep Med. 2023;19(3):591-594.