Advancing Primary Ciliary Dyskinesia Diagnosis through High-Speed Video Microscopy Analysis.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the PCD evaluation and diagnosis framework, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Evaluation of negative binomial and zero-inflated negative binomial models for the analysis of zero-inflated count data: application to the telemedicine for children with medical complexity trial.

BACKGROUND: Two characteristics of commonly used outcomes in medical research are zero inflation and non-negative integers; examples include the number of hospital admissions or emergency department visits, where the majority of patients will have zero counts. Zero-inflated regression models were devised to analyze this type of data. However, the performance of zero-inflated regression models or the properties of data best suited for these analyses have not been thoroughly investigated. METHODS: We conducted a simulation study to evaluate the performance of two generalized linear models, negative binomial and zero-inflated negative binomial, for analyzing zero-inflated count data. Simulation scenarios assumed a randomized controlled trial design and varied the true underlying distribution, sample size, and rate of zero inflation. We compared the models in terms of bias, mean squared error, and coverage. Additionally, we used logistic regression to determine which data properties are most important for predicting the best-fitting model. RESULTS: We first found that, regardless of the rate of zero inflation, there was little difference between the conventional negative binomial and its zero-inflated counterpart in terms of bias of the marginal treatment group coefficient. Second, even when the outcome was simulated from a zero-inflated distribution, a negative binomial model was favored above its ZI counterpart in terms of the Akaike Information Criterion. Third, the mean and skewness of the non-zero part of the data were stronger predictors of model preference than the percentage of zero counts. These results were not affected by the sample size, which ranged from 60 to 800. CONCLUSIONS: We recommend that the rate of zero inflation and overdispersion in the outcome should not be the sole and main justification for choosing zero-inflated regression models. Investigators should also consider other data characteristics when choosing a model for count data. In addition, if the performance of the NB and ZINB regression models is reasonably comparable even with ZI outcomes, we advocate the use of the NB regression model due to its clear and straightforward interpretation of the results.

Pulmonary outcomes of congenital diaphragmatic hernia patients based on defect size (CDH Study Group Stage).

Background: Congenital diaphragmatic hernia (CDH) is associated with significant pulmonary morbidity. Previous investigation has shown that postnatal inpatient morbidity is linked to diaphragmatic defect size. The objective of this study was to evaluate long-term pulmonary outcomes by CDH study group defect size. Methods: A retrospective analysis was conducted for CDH patients (n=133) managed in a neonatal intensive care unit (NICU) at a single children's hospital within an adult hospital system and subsequently followed up at a comprehensive multidisciplinary CDH clinic (n=102) from January 2012 to April 2022. CDH patients were stratified according to Congenital Diaphragmatic Hernia Study Group (CDHSG) Stage, and then categorized as low-risk (LR), defect size A and B, or high-risk (HR), defect size C and D. Inpatient data, including the presence of pulmonary hypertension, extracorporeal life support (ECLS) utilization, and mechanical ventilation days, were collected. Post-discharge data including the prevalence of asthma, pulmonary hypertension, emergency department visits, the total number of hospitalizations, and average rehospitalization days were collected. Frequentist analysis was used. Results: The outcomes for 133 NICU patients were analyzed (HR: n=54, LR: n=79). During NICU stay, the prevalence of pulmonary hypertension [HR: 16/54 (30%) vs. LR: 9/79 (12%), P=0.009], ECLS utilization [HR: 19/54 (35%) vs. LR: 4/79 (5%), P<0.001], and the average number of mechanical ventilation days [HR: 17 days (IQR: 12-27) vs. LR: 5 days (IQR: 2-9), P<0.001] were significantly higher in the HR CDH group. Post NICU discharge, the prevalence of asthma [HR: 20/54 (37%), vs. LR: 17/79 (22%), P=0.050)] and the total days of rehospitalization [HR: 9 (IQR: 2-27) vs. LR: 4 (IQR: 1-8), P=0.035] were significantly higher in HR group. Of the patients seen in the comprehensive multidisciplinary CDH clinic, obstructive lung disease measured by impulse oscillometry was increased in the HR CDH population compared to the reference group [median R5Hz was 12.95 kPa/(L/s) in CDH vs. 9.8 kPa/(L/s) (P=0.010)]. Conclusions: HR CDHSG Stage is associated with worse inpatient and long-term pulmonary outcomes.

Bronchiectasis Assessment in Primary Ciliary Dyskinesia: A Non-Invasive Approach Using Forced Oscillation Technique.

Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder that results from the dysfunction of motile cilia, which can cause chronic upper and lower respiratory infections leading to bronchiectasis. However, there is a need for additional tools to monitor the progression of bronchiectasis in PCD. The forced oscillation technique (FOT) is an effort-independent lung function test that can be used to evaluate respiratory mechanics. In this retrospective study, we aimed to describe the radiographic findings associated with respiratory impedance (resistance (Rrs) and reactance (Xrs)) measured by FOT in six adult PCD patients and one pediatric with the (RSPH4A (c.921+3_921+6delAAGT (intronic)) founder mutation. We compared the radiographic findings on a high-resolution chest computed tomography (CT) scan with the FOT results. Our findings suggest that respiratory impedance measured by FOT may be a valuable tool for detecting and monitoring the progression of bronchiectasis in PCD patients with the (RSPH4A (c.921+3_921+6delAAGT (intronic)) founder mutation. However, further research is necessary to validate these results and determine the sensitivity and specificity of bronchiectasis monitoring in PCD patients with other genetic mutations.

Screening for asthma in preschool children with sickle cell disease.

BACKGROUND: Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. METHODS: This is a prospective, single-center study of 50 children aged 2-5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. RESULTS: Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. CONCLUSION: The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea.

The RSPH4A Gene in Primary Ciliary Dyskinesia.

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has been described. The spectrum of the RSPH4A PCD phenotype does not include laterality defects, which results in a challenging diagnosis. PCD diagnostic tools can combine transmission electron microscopy (TEM), nasal nitric oxide (nNO), High-Speed Video microscopy Analysis (HSVA), and immunofluorescence. The purpose of this review article is to provide a comprehensive overview of current knowledge about the RSPH4A gene in PCD, ranging from basic science to human clinical phenotype.

Pulmonary hypertension screening in children with sickle cell disease.

BACKGROUND: Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. METHODS: Children (8-18 years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. RESULTS: A total of 73 patients were included (mean age 12 ± 5.7 years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5 m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. CONCLUSION: PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the island. The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD. The acquisition of state-of-the-art diagnostic tools such as nNO positively impacted and expanded our current PCD diagnostic capabilities in Puerto Rico for our founder genetic mutation. The addition of nNO technology promotes earlier disease screening and recognition for patients with PCD on the island. The access to nNO helped us to properly characterize the PCD diagnosis for patients with the RSPH4A (c.921+3_921+6del (intronic)). As a result, our findings will allow us to be part of the national PCD foundation registry and represent Puerto Rican Hispanics in future PCD multicentric clinical trials.

The Genetics of Primary Ciliary Dyskinesia in Puerto Rico.

Primary ciliary dyskinesia (PCD) has been linked to more than 50 genes that cause a spectrum of clinical symptoms, including newborn respiratory distress, sinopulmonary infections, and laterality abnormalities. Although the RSPH4A (c.921+3_6delAAGT) pathogenic variant has been related to Hispanic groups with Puerto Rican ancestry, it is uncertain how frequently other PCD-implicated genes are present on the island. A retrospective chart review of n = 127 genetic reports from Puerto Rican subjects who underwent genetic screening for PCD variants was conducted from 2018 to 2022. Of 127 subjects, 29.1% subjects presented PCD pathogenic variants, and 13.4% were homozygous for the RSPH4A (c.921+3_6delAAGT) founder mutation. The most common pathogenic variants were in RSPH4A and ZMYND10 genes. A description of the frequency and geographic distribution of implicated PCD pathogenic variants in Puerto Rico is presented. Our findings reconfirm that the presence of PCD in Puerto Rico is predominantly due to a founder pathogenic variant in the RSPH4A (c.921+3_6delAAGT) splice site. Understanding the frequency of PCD genetic variants in Puerto Rico is essential to map a future genotype-phenotype PCD spectrum in Puerto Rican Hispanics with a heterogeneous ancestry.

Sleep Apnea Screening in Children With Sickle Cell Anemia.

BACKGROUND: Screening for obstructive sleep apnea (OSA) is recommended by current guidelines in children with sickle cell anemia (SCA), but no specific approach is described. The Pediatric Sleep Questionnaire (PSQ) is a validated detection tool for OSA in children. We assessed the utility of PSQ to screen for OSA in children with concomitant SCA and snoring. MATERIALS AND METHODS: A prospective study, in children 4 to 18 years old with SCA. Subjects were assessed for snoring and PSQ administered at the same visit. All children with snoring were then referred for polysomnography. RESULTS: A total of 106 subjects were screened. Habitual snoring prevalence was 51/106 (48.1%). In the snoring group, OSA was detected in 83.9% (apnea-hypopnea index [AHI] ≥1.0/h) and 22.6% (AHI ≥5.0/h), respectively. Sensitivity and specificity of PSQ in children with snoring was 46.2% and 20.0% (AHI ≥1.0/h), and 57.1% and 50.0% (AHI ≥5.0/h), respectively. Physician assessment for snoring had a high sensitivity of 70.3% but low specificity of 58.4% (AHI ≥1.0/h), and 87.5% and 41.5% (AHI ≥5.0/h), respectively. CONCLUSION: PSQ is a poor screening tool for detection of OSA in those children with SCA who snore. Physician assessment for snoring could however be an initial approach before polysomnography.

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Primary Ciliary Dyskinesia: Ancestral Haplotypes Analysis of the RSPH4A Founder Mutation in Puerto Rico.

Genetic mutations in >50 genes, including RSPH4A, can lead to primary ciliary dyskinesia (PCD). RSPH4A mutations affect radial spokes, which alter the configuration of the ciliary ultrastructure and lead to chronic oto-sinopulmonary disease. The RSPH4A [c.921+3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. The average Puerto Rican genetic composition includes 64% European, 21% African ancestral, and 15% Native-American or Taino, a native tribe in the Caribbean at the start of the European colonization, genes. Due to the relatively elevated Taino ancestry on the island, it might have contributed to the endemicity of the RSPH4A [c.921+3_6delAAGT] splice site mutation. However, the ancestry of this mutation is still not confirmed. This article describes the two pediatric PCD cases with the Puerto Rican foundermutationand reports an ancestral haplotype analysis of the RSPH4A [c.921+3_6delAAGT] splice site mutation. A median-joining haplotype network was constructed with the genome sequence data from 104 Puerto Rican subjects in the 1000 Genomes Project (1000GP). This study found that the RSPH4A [c.921+3_6delAAGT] splice site mutation was carried to Puerto Rico from Europe by conquistadors or shortly after the conquest and that it gained frequency on the island through genetic drift fueled by a subsequent population expansion.

Telemedicine for Children With Medical Complexity: A Randomized Clinical Trial.

BACKGROUND: Telemedicine is widely used but has uncertain value. We assessed telemedicine to further improve outcomes and reduce costs of comprehensive care (CC) for medically complex children. METHODS: We conducted a single-center randomized clinical trial comparing telemedicine with CC relative to CC alone for medically complex children in reducing care days outside the home (clinic, emergency department, or hospital; primary outcome), rate of children developing serious illnesses (causing death, ICU admission, or hospital stay >7 days), and health system costs. We used intent-to-treat Bayesian analyses with neutral prior assuming no benefit. All participants received CC, which included 24/7 phone access to primary care providers (PCPs), low patient-to-PCP ratio, and hospital consultation from PCPs. The telemedicine group also received remote audiovisual communication with the PCPs. RESULTS: Between August 22, 2018, and March 23, 2020, we randomly assigned 422 medically complex children (209 to CC with telemedicine and 213 to CC alone) before meeting predefined stopping rules. The probability of a reduction with CC with telemedicine versus CC alone was 99% for care days outside the home (12.94 vs 16.94 per child-year; Bayesian rate ratio, 0.80 [95% credible interval, 0.66-0.98]), 95% for rate of children with a serious illness (0.29 vs 0.62 per child-year; rate ratio, 0.68 [0.43-1.07]) and 91% for mean total health system costs (US$33 718 vs US$41 281 per child-year; Bayesian cost ratio, 0.85 [0.67-1.08]). CONCLUSION: The addition of telemedicine to CC likely reduced care days outside the home, serious illnesses, other adverse outcomes, and health care costs for medically complex children.

Intravenous immunoglobulin as adjuvant therapy for COVID-19: A case report and literature review.

Severe acute respiratory syndrome coronavirus 2 has infected and caused the death of an alarming number of individuals worldwide. No specific treatment has been internationally standardized for coronavirus disease 2019 (COVID-19); however, in some cases, intravenous immunoglobulin (IVIG) has been used as adjuvant treatment in critically ill patients with COVID-19 pneumonia. We report a case of a 50-year-old man with severe COVID-19 pneumonia who received 5 days course of IVIG as adjuvant therapy. Invasive respiratory support was avoided. The patient had a successful recovery and was discharged without supplemental oxygen. A high dose of IVIG may improve survival in patients with severe COVID-19 pneumonia. In the current report, we reviewed literature on how IVIG use may improve the early stages of the disease.

Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican RSPH4A Founder Mutation.

Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than 45 genes, including RSPH4A, can lead to PCD. RSPH4A mutations located on chromosome six, affect radial spokes and results in central complex apparatus abnormalities. The RSPH4A [c.921 + 3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. Additionally, there are further diagnostic challenges present in the Puerto Rican population to diagnose PCD. We describe the demographics, clinical features, and RSPH4A genetic variants in 13 patients with clinical PCD affecting 11 Puerto Ricans from unrelated families.

First Characterization of the Formation of Anthocyanin-Ge and Anthocyanin-B Complexes through UV-Vis Spectroscopy and Density Functional Theory Quantum Chemical Calculations.

The occurrence of anthocyanin (ACN) and metal (Me) complexes has been widely supported by many research works while the possibility that ACNs bind to metalloids (Mds) is yet to be proven. Here, metalloids (H3BO3 for B; GeO2 for Ge) were added to cyanidin-based solutions at pH 5, 6, and 7 and ACN-Md stoichiometric ratios of 1:1, 1:10, 1:100, and 1:500, and UV-vis transmittance spectroscopy as well as density functional theory (DFT) calculations were performed to test this hypothesis. Ge and B addition caused bathochromic and hyperchromic shifts on ACN UV-vis spectra, particularly pronounced at pH 5 and a 1:500 (ACN:Md) ratio. ACN-Me complexation reactions have been evaluated where Ge showed a higher capability to bind to ACNs than B. Among the complexes envisioned, those labeled as b1, b2, and b3 feature UV-vis spectra compatible with experiments. The combination of experimental and computational data offers for the first time evidence of the formation of ACN-Md complexes.

Unexpected results of a randomized quality improvement program for children with severe asthma.

Objective: To assess whether an asthma intervention program reduces treatment days outside the home among children with severe asthma receiving comprehensive care (CC) in our center.Methods: Between October 21, 2014 and September 28, 2016, children with severe asthma were randomized to receive CC alone (n = 29) or CC plus the asthma intervention program (n = 34) which involved collaboration with pharmacists and school nurses, motivational interviewing, and tracking the one-second forced expiratory volume at home. All patients were followed through March 31, 2017. Frequentist and Bayesian intent-to-treat analyses were performed.Results: The asthma intervention program doubled the telephone calls between the staff and families (753 vs 356 per 100 child years for the intervention group vs. control group; Rate Ratio [RR], 2.11 [95% confidence interval, 1.29-3.45]). Yet, we found no evidence that it reduced the composite number of days of healthcare outside home which includes: clinic visits, ED visits, and hospital admissions (1179 vs 958 per 100 child-years in the intervention group vs. control group; [RR], 1.23 [95% CI, 0.82-1.84]) or secondary outcomes which are individual components (clinic visits, ED visits, hospitalizations, PICU admissions and school absences; RR 1.15 - 2.30; p > 0.05). Bayesian analysis indicated a 67% probability that the intervention program increases total treatment days outside the home and only a 14% probability of a true decrease of >20% as originally hypothesized.Conclusion: A multi-component intervention program provided to children with severe asthma failed to reduce and may have increased days of healthcare outside home and school absenteeism.

Validation of the breathmobile case identification survey for asthma screening in children with sickle cell disease.

Background: Asthma is a chronic airway disorder with variable/recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an inflammation. The expert panel report of the National Heart Lung and Blood Institute recommends asthma screening in sickle cell disease (SCD); however, specific approach is not mentioned. We hypothesize that the breathmobile case identification survey (BCIS) is a valid asthma screening tool in children with SCD.Methods: This prospective, single-center study enrolled 129 SCD patients aged 5 to 18 years from March 2016 to March 2018. All patients completed BCIS, spirometry, and fractional exhaled nitric oxide (FeNO). A single pulmonologist blinded to the BCIS results evaluated patients for asthma.Results: Asthma prevalence was 41%. Male gender (60.4%; p = 0.041), allergic rhinitis (86.8%; p < 0.01), hydroxyurea usage (73.6%; p < 0.01), and family history of asthma (34%; p < 0.01) were higher but not self-reported parental asthma history, eczema, and tobacco smoke exposure in the asthma group compared to the nonasthma group. FEV1 (p = 0.003), FVC (p = 0.02), FEV1/FVC (p = 0.053), and FEF25-75% (p = 0.02) were lower in asthma. FeNO levels were comparable in both groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated BCIS were 67.3%, 90.8%, 83.3%, and 80.2% for asthma; and 82.1%, 90.8%, 76.7%, and 93.2% for persistent asthma, respectively. Persistent asthma patients had a trend of higher hydroxyurea use (82.8% vs. 58.3%; p = 0.049) and tobacco smoke exposure (55.2% vs. 29.2%; p = 0.057) compared to intermittent asthma.Conclusion: We have validated the BCIS to screen for asthma in SCD. Spirometry but not FeNO may support an asthma diagnosis.

Hospital Consultation From Outpatient Clinicians for Medically Complex Children: A Randomized Clinical Trial.

Importance: Children with medical complexity (CMC) frequently experience fragmented care. We have demonstrated that outpatient comprehensive care (CC) reduces serious illnesses, hospitalizations, and costs for high-risk CMC. Yet continuity of care for CMC is often disrupted with emergency department (ED) visits and hospitalizations. Objective: To evaluate a hospital consultation (HC) service for CMC from their outpatient CC clinicians. Design, Setting, and Participants: Randomized quality improvement trial at the University of Texas Health Science Center at Houston with an outpatient CC clinic and tertiary pediatric hospital (Children's Memorial Hermann Hospital). Participants included high-risk CMC (≥2 hospitalizations or ≥1 pediatric intensive care unit [PICU] admission in the year before enrolling in our clinic) receiving CC. Data were analyzed between January 11, 2018, and December 20, 2019. Interventions: The HC included serial discussions between CC clinicians, ED physicians, and hospitalists addressing need for admission, inpatient treatment, and transition back to outpatient care. Usual hospital care (UHC) involved routine pediatric hospitalist care. Main Outcomes and Measures: Total hospital days (primary outcome), PICU days, hospitalizations, and health system costs in skeptical bayesian analyses (using a prior probability assuming no benefit). Results: From October 3, 2016, through October 2, 2017, 342 CMC were randomized to either HC (n = 167) or UHC (n = 175) before meeting the predefined bayesian stopping guideline (>80% probability of reduced hospital days). In intention-to-treat analyses, the probability that HC reduced total hospital days was 91% (2.72 vs 6.01 per child-year; bayesian rate ratio [RR], 0.61; 95% credible interval [CrI], 0.30-1.26). The probability of a reduction with HC vs UHC was 98% for hospitalizations (0.60 vs 0.93 per child-year; RR, 0.68; 95% CrI, 0.48-0.97), 89% for PICU days (0.77 vs 1.89 per child-year; RR, 0.59; 95% CrI, 0.26-1.38), and 94% for mean total health system costs ($24 928 vs $42 276 per child-year; cost ratio, 0.67; 95% CrI, 0.41-1.10). In secondary analysis using a bayesian prior centered at RR of 0.78, reflecting the opinion of 7 experts knowledgeable about CMC, the probability that HC reduced hospital days was 96%. Conclusions and Relevance: Among CMC receiving comprehensive outpatient care, an HC service from outpatient clinicians likely reduced total hospital days, hospitalizations, PICU days, other outcomes, and health system costs. Additional trials of an HC service from outpatient CC clinicians are needed for CMC in other centers. Trial Registration: ClinicalTrials.gov Identifier: NCT02870387.

Cardiac arrhythmias associated with volume-assured pressure support mode in a patient with autonomic dysfunction and mitochondrial disease.

NONE: A 15-year-old boy with autonomic dysfunction and mitochondrial disease was diagnosed with sleep-related hypoventilation at 6 years of age and treated with bilevel positive airway pressure therapy. At 12 years of age, treatment was transitioned to volume-assured pressure support (VAPS) due to clinical evidence of respiratory muscle weakness. Subsequent titration polysomnogram revealed the emergence of cardiac arrhythmia (isolated premature ventricular contractions, bigeminy, and trigeminy) while on VAPS mode that improved after transition to bilevel positive airway pressure therapy. During the titration study, higher tidal volumes correlated with increased pressures and the presence of arrhythmia. Prior to initiation of VAPS therapy, the patient had normal electrocardiogram evaluations. This case highlights the potential relationship between VAPS therapy and cardiac arrhythmias, especially in patients with underlying conditions with associated cardiac abnormalities, such as autonomic dysfunction and mitochondrial disease. While using VAPS mode, patients should be closely monitored for cardiac rhythm abnormalities.