Pilot Study of Group Interpersonal Psychotherapy for Depression Among Young People With Chronic Illness.

OBJECTIVE: Interpersonal psychotherapy (IPT) is an evidence-based treatment for depression, demonstrating efficacy with adolescents and young adults. Social support is proposed to be an important treatment component and may be helpful for adolescents and young adults with chronic illness. The authors sought to assess the feasibility of delivering IPT to this population and to examine changes in depressive symptoms and perceived social support. METHODS: An open-label feasibility trial of group-based IPT was conducted for adolescents and young adults with chronic illness (N=17). The 12-session group IPT was concurrent with group members' individual psychotherapy, and group IPT was focused on providing support in navigating interpersonal challenges related to the participants' chronic illness. Participants completed questionnaires assessing depressive symptoms and social support before treatment, midtreatment (6 weeks), and after treatment (12 weeks). Generalized estimating equation models, adjusted for repeated measures, were used to assess changes in depressive symptoms and social support over the course of treatment. RESULTS: Deidentified clinical examples illustrated how IPT was practiced in a community mental health setting. Evidence for the feasibility of group IPT was mixed. Although participants had poor session attendance, there was a significant decrease in depressive symptoms (ß=-2.94, 95% CI=-5.30 to -0.59, p=0.014) and a significant increase in perceived social support (ß=4.24, 95% CI=0.51 to 7.98, p=0.026) by the end of treatment. CONCLUSIONS: IPT may help address depressive symptoms and enhance social support among adolescents and young adults with chronic illness. Further research and adaptation are needed to address feasibility challenges in delivering group IPT to this population.

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients.

BACKGROUND: Venous thromboembolism (VTE) is a known complication among pediatric and adult cancer patients. Adolescent and young adult oncology (AYAO) patients have unique biological and physiological characteristics that make them distinct from other populations. Our objective was to study the VTE incidence, risk factors, and outcomes, which have been understudied in this population. PROCEDURE: A retrospective case-control study was conducted on AYAO participants with new or relapsed cancer and an imaging confirmed VTE from January 2011 to November 2016 at our institution. Eligible AYAO participants without a history of VTE were designated as controls and were randomly selected from our institution's tumor registry. Demographics, medical history, surgeries, central venous catheter (CVC) data, VTE diagnosis and treatment, relapses, and deaths were abstracted. RESULTS: Thirty-five VTE cases and 70 controls were included in this analysis. Eighty percent of cases had leukemia or lymphoma (vs. a solid tumor) compared to 58% of controls. The majority of VTEs (57%) were CVC associated, and more than 70% of cases had more than one CVC placed during their cancer treatment versus 34% of controls. Infection was associated with increased VTE risk (OR = 6.35, 95% CI = 2.30, 17.55, p < .0001). VTE cases had increased cancer relapse (23% vs. 10%) and mortality rates (29% vs. 16%) than controls. CONCLUSION: AYAO participants with a VTE were more likely to have leukemia or lymphoma, more than one CVC or infection. Further studies are needed to identify patients who would benefit from modifiable prevention measures, such as limiting to one CVC, preventing infections, or considering prophylactic anticoagulation for those with a liquid tumor.

Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test.

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21 years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

Food addiction, executive function and mood in adolescents with obesity seeking treatment.

BACKGROUND: The relationships between food addiction, executive functions and mood in adolescence are not well-understood. This study examines differences in executive functioning, depression symptoms and perceived stress among adolescents with obesity with- and without food addiction. METHODS: A total of 110 adolescents with obesity (74 females; age = 15.59 ± 1.3 y; 67% Hispanic; 74% public insurance) completed the Behavior Rating Inventory of Executive Function-2 (BRIEF-2), the Yale Food Addiction Scale for children (YFAS-c), the Perceived Stress Scale (PSS) and the Center for Epidemiologic Studies Depression scale (CES-DC). Chi-squared and Fisher's exact tests were used to evaluate differences in BRIEF-2, CES-DC and PSS scores between participants with and without food addiction. A logistic regression model assessed the associations between executive dysfunction, depression and stress on food addiction individually. Multiple logistic regression was utilized to further examine the association between executive dysfunction and food addiction when accounting for depression and stress. RESULTS: More than a third of participants (34.5%) met the criteria for food addiction. Females were 2.89 times more likely than males to have food addiction (95th%CI = 1.12-7.46, p = 0.03). Participants with FA had significantly higher BRIEF-2 T-scores (all p < 0.05) and higher PSS and CES-DC scores (all p < 0.05). Multiple logistic regression analysis showed depression was strongly correlated with FA when controlling for executive dysfunction and stress (p = 0.010). CONCLUSIONS: Among obesity treatment-seeking adolescents, youths with food addiction displayed greater impairments in executive functioning and higher levels of stress and depressive symptoms than adolescents without food addiction. Prospective studies are needed to determine how this behavioral phenotype helps predict intervention outcomes.

Anesthesia for pediatric patients with anti-NMDA receptor encephalitis: A retrospective case series.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor encephalitis is caused by auto-antibodies that target the N-methyl-D-aspartate receptor. Autonomic instability is a hallmark of the disease. The objective of this case series is to examine how anesthesia affects pediatric patients with this disease. METHODS: We performed a retrospective chart review of 28 records in 17 patients who underwent anesthesia. Our primary outcomes were hemodynamic changes during the perioperative period. Heart rate, systolic and diastolic blood pressures, respiratory rate, and oxygen saturation comprise our endpoints. A subgroup of patients, who underwent imaging with anesthesia, was then compared to controls. RESULTS: In anti-N-methyl-D-aspartate receptor encephalitis cases, there were significant percent changes from baseline in heart rate; median = -14.3%, 95% CI (-19.3, -9.0), p < .01 at 30 min and -15.7%, (-21.1, -9.8), p < .01 at 60 min; in systolic blood pressure, -19.4%, (-23.7, -14.8) at 30 min, p < .01, and -14.8%, (-19.7, -9.5) at 60 min, p < .01; in diastolic blood pressure, -41.9%, (-46.9, -36.3), p < .01 at 30 min, and -37.5%, (-43.4, -30.9), p < .01 at 60 min. When compared to controls, there were no significant differences between the two groups across time of anesthesia (baseline to 60 min) in heart rate (p = .24), systolic blood pressure (p = .30), and diastolic blood pressure (p = .11). No patients experienced hemodynamic lability under anesthesia. One patient, with severe symptoms, died within 24 h of anesthesia. CONCLUSION: Although pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis experienced vital sign changes with anesthesia, they were not clinically significant and they behaved similarly to controls. Disease severity may be a risk factor for perioperative complications.

Image-based ß-adrenergic sweat rate assay captures minimal cystic fibrosis transmembrane conductance regulator function.

BACKGROUND: There is a need to prognosticate the severity of cystic fibrosis (CF) detected by newborn screening (NBS) by early assessment of CF transmembrane conductance regulator (CFTR) protein function. We introduce novel instrumentation and protocol for evaluating CFTR activity as reflected by ß-adrenergically stimulated sweat secretion. METHODS: A pixilated image sensor detects sweat rates. Compounds necessary for maximum sweat gland stimulation are applied by iontophoresis, replacing ID injections. Results are compared to a validated ß-adrenergic assay that measures sweat secretion by evaporation (evaporimetry). RESULTS: Ten healthy controls (HC), 6 heterozygous (carriers), 5 with CFTR-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID), and 12 CF individuals completed testing. All individuals with minimal and residual function CFTR mutations had low ratios of ß-adrenergically stimulated sweat rate to cholinergically stimulated sweat rate (ß/chol) as measured by either assay. CONCLUSIONS: ß-Adrenergic assays quantitate CFTR dysfunction in the secretory pathway of sweat glands in CF and CRMS/CFSPID populations. This novel image-sensor and iontophoresis protocol detect CFTR function with minimal and residual function and is a feasible test for young children because it is insensible to movement and it decreases the number of injections. It may also assist to distinguish between CF and CRMS/CFSPID diagnosis.

Abnormal Lung Clearance Index in Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Children with Otherwise Normal FEV1.

In preschool children with cystic fibrosis (CF), lung clearance index (LCI) is a sensitive test to detect early lung disease. Some children with CF screen positive, inconclusive diagnosis (CFSPID) may in time develop clinical features of CF. LCI has not been studied in CFSPID children. LCI and spirometry were performed in preschool age children with CF, CFSPID, and non-CF healthy controls (HCs) during two visits. Fifty-four preschool age children (HC n = 18, CFSPID n = 17, and CF n = 19) were tested. Mean LCI from the CFSPID group was not statistically different from HC (p = 0.49), but significantly different when compared to CF (p = 0.04). LCI was abnormal in 2 CFSPID children who carried potentially deleterious CFTR variants. Mean forced expiratory volume in 1 s (FEV1) was not statistically different between CFSPID and CF (p = 0.26). LCI can potentially detect early lung disease in CFSPID individuals as part of assessing their risk for reclassification to CF diagnosis.

Evaluation of Obstructive Sleep Apnea in Prone Versus Nonprone Body Positioning With Polysomnography in Infants With Robin Sequence.

OBJECTIVE: Management of obstructive sleep apnea in infants with Robin sequence (RS) includes prone positioning during sleep, which conflicts with safe infant sleep data. We examined changes in polysomnography (PSG) parameters for prone versus nonprone body positions in these infants. DESIGN: Pre-post interventional, nonblinded study. PARTICIPANTS: Infants with RS referred for PSG were recruited from craniofacial clinic and inpatient units at Children's Hospital Los Angeles, a tertiary pediatric center. Fourteen infants were recruited, and 12 studies were completed on both body positions; 11 studies were used in the analysis. INTERVENTIONS: The PSG was divided into nonprone and prone sleep, moving from their usual sleep position to the other position midway in the study. MAIN OUTCOME MEASURES: Data was collected in each position for obstructive apnea-hypopnea index (oAHI), central apnea index (CAI), sleep efficiency (SE), and arousal index (AI). Signed rank test was used to evaluate the change in body position. RESULTS: All infants were term except 1, age 7 to 218 days (mean: 55 days; standard deviation: 58 days), and 8 (57%) of 14 were female. From nonprone to prone sleep position, the median oAHI (16.0-14.0), CAI (2.9-1.0), and AI (28.0-19.9) decreased (P = .065); SE increased (67.4-85.2; P = .227). CONCLUSIONS: Prone positioning may benefit some infants with RS. However, even those with significant improvement in obstructive sleep apnea did not completely resolve their obstruction. The decision to use prone positioning as a therapy should be objectively evaluated in individual infants.

A 4D flow MRI evaluation of the impact of shear-dependent fluid viscosity on in vitro Fontan circulation flow.

The Fontan procedure for univentricular heart defects creates a nonphysiologic circulation where systemic venous blood drains directly into the pulmonary arteries, leading to multiorgan dysfunction secondary to chronic low-shear nonpulsatile pulmonary blood flow and central venous hypertension. Although blood viscosity increases exponentially in this low-shear environment, the role of shear-dependent ("non-Newtonian") blood viscosity in this pathophysiology is unclear. We studied three-dimensional (3D)-printed Fontan models in an in vitro flow loop with a Philips 3-T magnetic resonance imaging (MRI) scanner. A 4D flow phase-contrast sequence was used to acquire a time-varying 3D velocity field for each experimental condition. On the basis of blood viscosity of a cohort of patients who had undergone the Fontan procedure, it was decided to use 0.04% xanthan gum as a non-Newtonian blood analog; 45% glycerol was used as a Newtonian control fluid. MRI data were analyzed using GTFlow and MATLAB software. The primary outcome, power loss, was significantly higher with the Newtonian fluid [14.8 (13.3, 16.4) vs. 8.1 (6.4, 9.8)%, medians with 95% confidence interval, P < 0.0001]. The Newtonian fluid also demonstrated marginally higher right pulmonary artery flow, marginally lower shear stress, and a trend toward higher caval flow mixing. Outcomes were modulated by Fontan model complexity, cardiac output, and caval flow ratio. Vortexes, helical flow, and stagnant flow were more prevalent with the non-Newtonian fluid. Our data demonstrate that shear-dependent viscosity significantly alters qualitative flow patterns, power loss, pulmonary flow distribution, shear stress, and caval flow mixing in synthetic models of the Fontan circulation. Potential clinical implications include effects on exercise capacity, ventilation-perfusion matching, risk of pulmonary arteriovenous malformations, and risk of thromboembolism.NEW & NOTEWORTHY Although blood viscosity increases exponentially in low-shear environments, the role of shear-dependent ("non-Newtonian") blood viscosity in the pathophysiology of the low-shear Fontan circulation is unclear. We demonstrate that shear-dependent viscosity significantly alters qualitative flow patterns, power loss, pulmonary flow distribution, shear stress, and caval flow mixing in synthetic models of the Fontan circulation. Potential clinical implications include effects on exercise capacity, ventilation-perfusion matching, risk of pulmonary arteriovenous malformations, and risk of thromboembolism.

Improving Disaster Preparedness of Families With a Parenteral Nutrition-dependent Child.

OBJECTIVES: Disruption in the care of special healthcare needs children may lead to life-threatening situations or preventable secondary conditions. California averages more than 100 earthquakes per week. Subsequent power outages, damage to utility systems, and road damage after an earthquake can have grave consequences for families with parenteral nutrition (PN)-dependent children. The purpose of the study was to demonstrate that we could improve disaster preparedness of families with PN-dependent children utilizing individualized family education and distribution of personalized disaster survival toolkits. METHODS: We administered a baseline survey to assess disaster preparedness of our families with PN-dependent children followed by individualized disaster survival toolkit distribution and education. We followed up with these families with phone call surveys at 2 and 4 months. A generalized estimating equation with both logistic and linear regression was used to analyze data over the follow-up period. RESULTS: We found statistically significant improvements in developing a family emergency plan (P < 0.0001), having a basic emergency supply kit (P < 0.0001), having a completed emergency information form from the child's provider (P < 0.0001), and the confidence level or readiness for a disaster (P < 0.0001). All participants had extra batteries for PN infusion pumps. Having alternative power sources, such as a generator, did not significantly change over time. CONCLUSIONS: Individualized disaster education helped families with PN-dependent children not only to prepare for a possible earthquake, but also to feel more confident in their ability to handle a natural disaster.

Bacteremia in nonneutropenic pediatric oncology patients with central venous catheters in the ED.

OBJECTIVE: To examine clinical characteristics associated with bacteremia in febrile nonneutropenic pediatric oncology patients with central venous catheters (CVCs) in the emergency department (ED). BACKGROUND: Fever is the primary reason pediatric oncology patients present to the ED. The literature states that 0.9% to 39% of febrile nonneutropenic oncology patients are bacteremic, yet few studies have investigated infectious risk factors in this population. METHODS: This was a retrospective cohort study in a pediatric ED, reviewing medical records from 2002 to 2014. Inclusion criteria were patients with cancer, temperature at least 38°C, presence of a CVC, absolute neutrophil count greater than 500 cells/µL, and age less than 22 years. Exclusion criteria were repeat ED visits within 72 hours, bloodwork results not reported by the laboratory, and patients without oncologic history documented at the study hospital. The primary outcome measure is a positive blood culture (+BC). Other variables include age, sex, CVC type, cancer diagnosis, absolute neutrophil count, vital signs, upper respiratory infection (URI) symptoms, and amount of intravenous (IV) normal saline (NS) administered in the ED. Data were analyzed using descriptive statistics and a multiple logistic regression model. RESULTS: A total of 1322 ED visits were sampled, with 534 enrolled, and 39 visits had +BC (7.3%). Variables associated with an increased risk of +BC included the following: absence of URI symptoms (odds ratio [OR], 2.30; 95% CI, 1.13-4.69), neuroblastoma (OR, 3.65; 95% CI, 1.47-9.09), "other" cancer diagnosis (OR, 4.56; 95% CI, 1.93-10.76), tunneled externalized CVC (OR, 5.04; 95% CI, 2.25-11.28), and receiving at least 20 mL/kg IV NS (OR, 2.34; 95% CI, 1.2-4.55). The results of a multiple logistic regression model also showed these variables to be associated with +BC. CONCLUSION: The absence of URI symptoms, presence of an externalized CVC, neuroblastoma or other cancer diagnosis, and receiving at least 20 mL/kg IV NS in the ED are associated with increased risk of bacteremia in nonneutropenic pediatric oncology patients with a CVC.

Pulmonary function abnormalities in childhood cancer survivors treated with bleomycin.

BACKGROUND: Bleomycin is associated with pulmonary toxic side effects including pneumonitis and pulmonary fibrosis. We evaluated the prevalence of long-term pulmonary function abnormalities in children receiving bleomycin therapy in the context of current chemotherapeutic regimens. METHODS: A retrospective review of patients who received bleomycin between January 1999 and December 2011 was conducted. Abnormalities in the most recent pulmonary function test (PFT) at least 1 year after diagnosis were analyzed. RESULTS: Two-hundred and seven patients had received bleomycin. The results of PFT performed at least 1 year from diagnosis were available for 80 patients. Median time of follow up was 3.9 years (range 1.1-11.76 years). Median cumulative dose of bleomycin was 65 IU/m(2) (range 10-120). The most common diagnoses were Hodgkin lymphoma and germ cell tumor. At least one pulmonary function abnormality was present in 42 (52.5%) patients. When classified in groups, 22.5% patients had obstructive lung disease, 7.5% had restrictive lung disease, 28.8% had hyperinflation and 14% of patients had non-uniform distribution of ventilation. Non-Hispanic patients (OR 2.81) and children younger than 8 years (OR 4.14) had higher odds of having an abnormal PFT parameter. Very few patients had pulmonary symptoms. CONCLUSIONS: More than half the patients who received bleomycin had subclinical pulmonary dysfunction as evidenced by abnormalities in pulmonary function tests, although the incidence of clinical symptoms was low.

A Survey of Skin Reactions Associated With Acrylic Nail Cosmetics, With a Focus on Home Kits: Is There a Need for Regulation?

Background: Sensitization to (meth)acrylates, the most common nail cosmetic allergens, is rising. In recent years, home acrylic nail kits have become easily available. Objective: To investigate the characteristics of individuals reporting skin reactions associated with acrylic nail cosmetics, particularly home kits. Methods: Cross-sectional survey of Facebook nail allergy support groups. Inclusion criteria were self-reported skin reactions associated with acrylic nails and age ≥18 years. Results: There were 199 respondents, nearly all female (99%), mostly white (83%), and 25-54 years old (83%). Seventy-eight percent reported using home acrylic kits, more than half for the first time during COVID-19. They predominantly learned about kits through social media (68%) and received training through websites/online videos (74%). Most home users (83%) first developed skin reactions after starting to use home kits. Compared with nonhome users, significantly more home users reported skin reaction onset within 1 year of use, as well as nail damage (P < 0.05). Conclusions: Among online nail allergy support group members, home acrylic nail kit use was common and associated with earlier development of skin reactions and more frequent nail damage than professional acrylic manicures. These findings raise important questions about the need to regulate home acrylic nail kits.

Timing of meal consumption on glucose profiles in Latino adolescents with obesity.

INTRODUCTION: To date, there has been no study investigating how meal-timing impacts glucose and insulin resistance among Latino youth at high risk of type 2 diabetes. A proof-of-concept study was conducted to assess metabolic response to a test-meal consumed in the morning, afternoon, and evening among 15 Latino adolescents with obesity using a within-participant design. METHODS: Youth, 13 to 19 years of age, with obesity, consumed the same test-meal after a 16 hour fast at three different times on separate days. Immediately after consumption of the test meal, a mixed meal tolerance test (MMTT) was performed. The co-primary outcomes were the area under the curve (AUC) for glucose, insulin, and c-peptide, and insulinogenic index (IGI). RESULTS: Twenty-two youth consented to participate for a 24% recruitment rate (78% female, 100% Latino, mean age 16.5±1.3 years, 70% publicly insured). There was a significantly greater rise in glucose and c-peptide levels following at 4 PM compared to 8 AM (glucose: p = 0.006; c-peptide: p < 0.0001) with no significant association found between insulin levels and timing of meal consumption. Pairwise comparisons showed a greater rise in AUC glucose and c-peptide levels at 4 PM compared to 8 AM (glucose p = 0.003; c-peptide p < 0.001) with no significant association found between insulin AUC and timing of meal consumption (p = 0.09). There was a greater reduction in IGI at 4 PM compared to 8 AM (p = 0.027). CONCLUSION: Similar to findings in adults at risk for diabetes, Latino youth with obesity show greater insulin resistance in response to a meal consumed in the afternoon and evening compared to early morning food consumption.

The association between integrating echocardiography use in the management of septic shock patients and outcomes in the intensive care unit: a systematic review and meta-analysis.

OBJECTIVES: Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines. METHODS: An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data. RESULTS: A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87 h [95%CI - 1.23 h to - 0.51 h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11 ml [95%CI - 5.93 ml to 1.72 ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03 days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome. CONCLUSIONS: POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU.

Cystic Fibrosis Screen Positive, Inconclusive Diagnosis Genotypes in People with Cystic Fibrosis from the U.S. Patient Registry.

Rationale: Variants within the cystic fibrosis (CF) transmembrane conductance regulator gene, CFTR, that are of unknown significance or are categorized as non-CF causing may be observed in persons with CF. These variants are frequently detected in children with inconclusive newborn screen results and, in some cases, may be associated with a benign presentation in early childhood that progresses to a CF phenotype later in life. Objectives: To analyze data from individuals enrolled in the U.S. Cystic Fibrosis Foundation Patient Registry who have received a diagnosis of CF and who have variants found in a population of children with a CF screen positive, inconclusive diagnosis (CFSPID). Methods: This retrospective review analyzed registry data from individuals with a diagnosis of CF who also harbor one or more variants of interest because of their frequency within a CFSPID population and/or their interpretation as non-CF causing. Three groups were defined by the number of CF-causing variants identified (CF-Cx2, CF-Cx1, and CF-Cx0), which were reported in addition to the variant(s) of interest. Multivariate quantile regression modeling of the outcome for forced expiratory volume in 1 second (FEV1) generated a disease severity score for each person determined by six selected variables. Median scores were calculated for the three groups. Results: Patients carrying one CF-causing variant and at least one variant of interest (CF-Cx1) had higher median disease severity scores compared with those carrying CF-Cx2, suggesting a milder phenotype (P < 0.05). However, there was no statistically significant difference in scores between CF-Cx2 and the two other groups combined (CF-Cx1 and CF-Cx0; P = 0.33). Analysis revealed that the CF-Cx1 and CF-Cx0 groups, when compared with the CF-Cx2 group, had later median diagnoses (8 years vs. newborn; P < 0.0001), lower median sweat chloride (48 mmol/L vs. 94.5 mmol/L; P < 0.0001), lower prevalence of pancreatic insufficiency (29% vs. 78%; P < 0.0001), and higher median FEV1% predicted (95% vs. 87%; P = 0.0002). Conclusions: Individuals with CF who have specific variants frequently identified in children with CFSPID have a similar range of disease severity scores compared with those who have two CF-causing variants, but a milder phenotype overall. Variants that should be given careful scrutiny because of their high prevalence are G576A+R668C, T854T, R75Q, F1052V, R1070W, R31C, and L967S.

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification.

OBJECTIVES: Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen-positive, inconclusive diagnosis (CFSPID), with limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are not well established. We investigated whether clinical characteristics are associated with the risk of reclassification from CFSPID to a CF diagnosis. METHODS: Children with a positive CF NBS were recruited from two sites in California. Retrospective, longitudinal, and cross-sectional data were collected. A subset of subjects had nasal epithelial cells collected for CF transmembrane conductance regulator (CFTR) functional assessment. Multivariate logistic regression was used to assess the risk of reclassification. RESULTS: A total of 112 children completed the study (CF = 53, CFSPID = 59). Phenotypic characteristics between groups showed differences in pancreatic insufficiency prevalence, immunoreactive trypsinogen (IRT) levels, and Pseudomonas aeruginosa (PSA) colonization. Spirometry measures were not different between groups. Nasal epithelial cells from 10 subjects showed 7%-30% of wild-type (WT)-CFTR (wtCFTR) function in those who reclassified and 27%-67% of wtCFTR function in those who retained the CFSPID designation. Modeling revealed that increasing sweat chloride concentration (sw[Cl- ]) and PSA colonization were independent risk factors for reclassification to CF. CONCLUSION: Increasing sw[Cl- ] and a history of PSA colonization are associated with the risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. A close follow-up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration.

Impact of 8-hour time-limited eating on sleep in adolescents with obesity.

STUDY OBJECTIVES: The relationship between time-limited eating (TLE) and sleep quality is a topic of growing interest in the field of chronobiology. Data in adult cohorts shows that TLE may improve sleep quality, but this has not been evaluated in adolescents. The aim of this secondary analysis was to (1) examine the impact of 8-hour TLE on sleep parameters in youth with obesity and (2) explore if there was any association between sleep patterns and glycemic profiles. METHODS: Adolescents with obesity were randomized into one of three groups: 8-hour TLE (participants self-selected their eating window) + real-time continuous glucose monitor, 8-hour TLE + blinded continuous glucose monitor, or a prolonged eating window. In the primary analysis, it was found that participants in the real-time continuous glucose monitor group + 8-hour TLE group did not access their continuous glucose monitor data and thus for this analysis the two TLE groups were combined and only completers who had available Pittsburgh Sleep Quality Index (PSQI) data at all three time points were included. Participants completed the PSQI at baseline, week 4, and week 12. Mixed-effects generalized linear regression models were utilized to examine the change in PSQI score and assess association between glycemic variability and PSQI total score overtime by intervention arm. RESULTS: The median PSQI total score for the TLE groups (n = 27) was 6 at week 0 (interquartile range = 5 to 10) and 5 at week 12 (interquartile range = 2 to 7). There was no significant difference in the change in total PSQI score or sleep latency between TLE and control over the study period (P > .05). There was no association between PSQI score and change in weight or glycemic profile between groups (all P values > 0.05). CONCLUSIONS: These results suggest that in adolescents with obesity, an 8-hour TLE approach did not negatively impact sleep quality or efficiency when compared to a prolonged eating window. The potential effects of TLE on sleep should be further investigated in larger randomized trials. CITATION: Jayakumr A, Gillett ES, Wee CP, Kim A, Vidmar AP. Impact of 8-hour time-limited eating on sleep in adolescents with obesity. J Clin Sleep Med. 2023;19(11):1941-1949.

An addiction-based digital weight loss intervention: A multi-centre randomized controlled trial.

OBJECTIVE: This randomized clinical trial tested the effectiveness of an addiction-based digital weight-loss intervention, focusing on withdrawal/abstinence from self-identified problem foods, snacking and excessive amounts at meals, and discomfort displacement, with and without coaching, compared to an in-person, multi-disciplinary, care model among adolescents with obesity. We hypothesized that the digital intervention with coaching would yield greater weight loss and lower delivery burden than the standard clinical arm, and greater participant engagement than the digital arm without coaching. METHODS: Adolescents were randomized to app intervention, with or without coaching, or in-person multidisciplinary obesity intervention for 6 months. The primary outcome was change in %BMIp95 at weeks 12 and 24. A mixed-effects linear regression model was used to assess the association between change in %BMIp95 and intervention arm. We were also interested in assessing delivery burden, participant engagement and evaluating the relationships between weight change and demographic characteristics, mood, executive function and eating behaviours. RESULTS: All adolescents (n = 161; BMI ≥95th%, age 16 ± 2.5 year; 47% Hispanic, 65% female, 59% publicly insured) lost weight over 24-weeks (-1.29%, [-1.82, -0.76], p < 0.0001), with no significant weight loss difference between groups (p = 0.3). Girls lost more weight than boys, whereas binge eating behaviour at baseline was associated with increase in %BMIp95 when controlling for other covariates. There was no association between ethnicity, mood, timing of intervention in relation to the pandemic, or executive function and change in %BMIp95 . CONCLUSIONS: Contrary with our hypothesis, our results showed no difference in the change in BMI status between treatment arms. Since efficacy of this digital intervention was not inferior to in-person, multi-disciplinary care, this could offer a reasonable weight management option for clinicians, based on youth and family specific characteristics, such as accessibility, resources, and communication styles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT035008353.