Effect of Hypertonic Saline on Lung Function as Add-on Treatment in People With Cystic Fibrosis Receiving Dornase Alfa: A Cystic Fibrosis Foundation Patient Registry Analysis.

BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1 to 5 years without DA or HS during the preceding (baseline) year. Absolute FEV1 % predicted change while receiving DA and HS, relative to treatment with DA only, was the main outcome. A marginal structural model was applied to assess the effect of 1 to 5 years of HS treatment while controlling for time-dependent confounding. RESULTS: Of 1,241 CFF508del, 619 patients (median baseline age, 14.6 years; interquartile range, 6-53 years) received DA only and 622 patients (median baseline age, 14.55 years; interquartile range, 6-48.1 years) were treated with DA and HS for 1 to 5 years. After 1 year, patients receiving DA and HS showed FEV1 % predicted that averaged 6.60% lower than that in patients treated with DA only (95% CI, -8.54% to -4.66%; P < .001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's FEV1 % predicted, and time-varying clinical characteristics, patients treated with DA and HS for 1 to 5 years were similar to those treated with DA only regarding FEV1 % predicted (year 1: mean FEV1 % predicted change, +0.53% [95% CI, -0.66% to +1.71%; P = .38]; year 5: mean FEV1 % predicted change, -1.82% [95% CI, -4.01% to +0.36%; P = .10]). INTERPRETATION: In the era before modulators, CFF508del showed no significant difference in lung function when nebulized HS was added to DA for 1 to 5 years.

Topical Pharyngeal Anesthesia in Sedated Pediatric Patients Undergoing Esophagogastroduodenoscopy.

OBJECTIVES: Pediatric patients undergoing esophagogastroduodenoscopy (EGD) commonly receive procedural sedation for comfort and to facilitate the procedure. EGD with procedural sedation carries the risk of several airway incidents and/or adverse events (AIAE). Topical pharyngeal anesthetics (TPAs) can blunt the airway reflexes and decrease the incidence of laryngospasm but has not been well studied with EGD under procedural sedation. We aimed to study the effect of adding a TPA to propofol-based sedation on the rate of AIAE. METHODS: This is a single-center, retrospective, observational cohort study. We compare AIAE rates (coughing, gagging, apnea, airway obstruction, and laryngospasm) in children who received TPA as part of their propofol-based procedural sedation for EGD with those who did not receive TPA. RESULTS: In 2021, 73 patients received TPA as part of the procedural sedation for EGD and 123 did not. The overall rate of AIAE was high with 75 (38%) patients experiencing 1 or more AIAE. Patients who received benzocaine spray experienced more AIAE than the control group [adjusted odds ratio (aOR) = 1.16; 95% confidence interval (CI): 1.01-1.34; P = 0.037]. Coughing, gagging, apnea with desaturation rates, and laryngospasm were similar in both groups (coughing aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; gagging aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; apnea aOR = 0.99; 95% CI: 0.95-1.04; P = 0.688; laryngospasm OR = 1.01; 95% CI: 0.95-1.07; P = 0.71). The rate of airway obstruction requiring jaw thrust was higher in the benzocaine group but did not reach statistical significance (aOR = 1.11; 95% CI: 0.97-1.26; P = 0.133). CONCLUSION: The use of topical pharyngeal benzocaine in children undergoing EGD with propofol-based sedation is associated with a higher overall AIAE rate. Most of the AIAE were mild incidents and only 7 patients experienced true adverse events.

A Survey of Academic Neonatologists on Neonatal Electrical Cardioversion and Defibrillation.

OBJECTIVE: This study aimed to assess neonatologists' experience and comfort with neonatal electrical cardioversion or defibrillation (EC-D). STUDY DESIGN: Electronic surveys were distributed to academic neonatologists affiliated with 12 Midwest academic hospitals. Neonatologists were asked about their residency training; years since completing residency; current certification/competency training in the Basic Life Support (BLS), Pediatric Advanced Life Support (PALS), Advanced Cardiovascular Life Support (ACLS), and Neonatal Resuscitation Program (NRP); experiences with EC-D; availability of a pediatric cardiologist; and their comfort levels with such procedures. Standard statistical tests evaluated comfort with EC-D. RESULTS: Seventy-two out of 180 neonatologists responded to the survey (response rate = 40%). Of them, 98.6% (71), 54.2% (39), and 37.5% (27) maintained current NRP, BLS, and PALS trainings, respectively. Also, 73.6% (n = 53) reported having performed neonatal EC-D. Of those, 50.9% (n = 27) indicated feeling slightly to very uncomfortable performing EC-D. We report a lack of BLS certification being associated with a lack of comfort (odds ratio [OR]: 0.269, 95% confidence interval [CI]: [0.071, 0.936]), and a positive association between a pediatric cardiologist being present and being uncomfortable (OR: 3.722, 95% CI: [1.069, 14.059]). Those reporting greater volume and more recent experience with EC-D report more comfort. CONCLUSION: Of neonatologists who performed EC-D, half of them reported being uncomfortable. BLS certification and experience are positively associated with comfort in performing EC-D. Simulations to increase training in EC-D should be offered regularly to academic neonatologists. KEY POINTS: · Most neonatologists have performed EC-D, but many feel uncomfortable with performing EC-D.. · Many do not maintain current certification in BLS, PALS, or ACLS.. · Simulation training in EC-D will increase comfort with EC-D..

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings.

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9-9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19-1.51); and OR 4.10, 95% CI 2.06-8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842-0.964] versus 0.745 [95% CI 0.668-0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.

SARS-CoV-2 and influenza co-infection: A cross-sectional study in central Missouri during the 2021-2022 influenza season.

As SARS-CoV-2 and influenza viruses co-circulate, co-infections with these viruses generate an increasing concern to public health. To evaluate the prevalence and clinical impacts of SARS-CoV-2 and influenza A virus co-infections during the 2021-2022 influenza season, SARS-CoV-2-positive samples from 462 individuals were collected from October 2021 to January 2022. Of these individuals, 152 tested positive for influenza, and the monthly co-infection rate ranged from 7.1% to 48%. Compared to the Delta variant, individuals infected with Omicron were less likely to be co-infected and hospitalized, and individuals who received influenza vaccines were less likely to become co-infected. Three individuals had two samples collected on different dates, and all three developed a co-infection after their initial SARS-CoV-2 infection. This study demonstrates high prevalence of co-infections in central Missouri during the 2021-2022 influenza season, differences in co-infection prevalence between the Delta and the Omicron waves, and the importance of influenza vaccinations against co-infections.

Infections and antibiotic use in early life, and obesity in early childhood: a mediation analysis.

BACKGROUND/OBJECTIVE: Literature shows a positive association between antibiotics and obesity in childhood, but fails to account for confounding by indication. We evaluate the direct effect of infection on obesity and the indirect effect mediated by antibiotics by performing a mediation analysis of the infection-obesity association. METHODS: A Medicaid cohort of children age 2-14 years old between 2015-2019 (n = 61,330) is used to perform mediation analysis of infections and antibiotic use in the first year of life, and obesity in childhood in Missouri, U.S.A. RESULTS: An additional infection increases the risk of obesity in childhood (aIRR = 1.050, p < 0.001); however, mediation by antibiotic use is clinically and statistically insignificant. If the number of infections is not considered in the analysis, then antibiotic use as a risk factor for obesity is overstated (aIRR = 1.037 vs. 1.013 p < 0.001). CONCLUSIONS: The number of infections exhibits a significant relationship with obesity and is a stronger risk factor for obesity than antibiotic use. In particular, a greater number of bronchitis, otitis media, and upper respiratory infections in the first year of life are associated with a significant increased risk of obesity in childhood. We find only weak evidence that an additional antibiotics claim increases the risk of obesity in childhood and this risk may not be clinically meaningful. Further research is needed to explore the association between early childhood infections, especially in the first 6 months of life, and obesity including the biological mechanism and environmental factor of early life infections associated with obesity.

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.

The Life Course of Unemployment and Midlife Health.

Objectives: We estimate associations between unemployment trajectories from ages 27-49 and physical and mental health at age 50. Methods: Data are from the U.S. National Longitudinal Survey of Youth, 1979 (N=6434). Group-based trajectory models are used to identify unemployment trajectories. Generalized linear models with a modified Bolck, Croon, and Hagenaars (BCH) correction are used to regress health on unemployment trajectory groups. Results: We identified "Consistently Low (70%)," "Decreasing Mid-Career (18%)," and "Persistently High (12%)" unemployment trajectories. Experiencing Decreasing Mid-Career or Persistently High trajectories was associated with worse physical and mental health at age 50 than Consistently Low trajectories. Experiencing a Persistently High trajectory was associated with worse physical and mental health than a Decreasing Mid-Career trajectory. Discussion: Timing and likelihood of unemployment are associated with midlife health. Mid-Career unemployment is associated with worse physical and mental health at age 50, but not to the same degree as Persistently High unemployment.

Coronavirus Disease 2019 (COVID-19) Disease Severity: Pregnant vs Nonpregnant Women at 82 Facilities.

BACKGROUND: Pregnancy has been reported to be a risk factor for severe COVID-19. We evaluated the impact of pregnancy on severe COVID-19 and mortality in an electronic medical record (EMR) database that enabled exclusion of labor and delivery (L&D) encounters. METHODS: In this retrospective cohort study, EMRs from 82 healthcare facilities in the Cerner COVID-19 Datamart were analyzed. The study comprised 38 106 individuals aged 18-45 years old with COVID-19 who had emergency department, urgent care, or inpatient encounters from December 2019 to September 2020. Subgroups were balanced through propensity score weights for age, race, smoking status, and number of comorbidities. The primary outcome was COVID-19-related mortality; secondary outcomes were markers of severe COVID-19: intubations, mechanical ventilation, use of vasopressors, diagnosis of sepsis, and diagnosis of acute respiratory distress syndrome. RESULTS: In comparing pregnant and nonpregnant women, no statistical differences were found for markers of severe COVID-19, after adjusting for age, smoking, race, and comorbidities. The adjusted odds of an inpatient encounter were higher for pregnant vs nonpregnant women (adjusted odds ratio [aOR], 13.2; 95% confidence interval [CI], 11.6-15.3; P < .001), but notably lower after excluding L&D encounters (aOR, 2.3; 95% CI, 1.89-2.88; P < .001). In comparison to women without L&D encounters, hospitalization was significantly more likely for men. CONCLUSIONS: We did not find an increased risk of severe COVID-19 or mortality in pregnancy. Hospitalization does not necessarily indicate severe COVID-19 in pregnancy, as half of pregnant patients with COVID-19 were admitted for L&D encounters in this study.

Association of Sleep-disordered Breathing and Blood Pressure with Albuminuria: The Nagahama Study.

Rationale: Although sleep-disordered breathing (SDB) may increase urinary albumin excretion (UAE) by raising nocturnal blood pressure (BP) in addition to diurnal BP, the correlation has not been investigated in a general population. Objectives: To evaluate the relationships among UAE, SDB, and BP during sleep in a large population cohort. Methods: Among 9,850 community residents, UAE was assessed by the urinary albumin-to-creatinine ratio (UACR) in spot urine. Sleep duration and SDB were evaluated by a wearable actigraph and pulse oximeter, respectively. We calculated the actigraphy-modified 3% oxygen desaturation index (Acti-3%ODI) by correcting the time measured by pulse oximetry according to sleep duration obtained by actigraphy. Furthermore, participants were instructed to measure morning and sleep BP at home by a timer-equipped oscillometric device. Results: Measurements of sleep parameters, UAE, and office BP were obtained in 6,568 participants. The multivariate analysis that included confounders showed a significant association of Acti-3%ODI with UACR (ß = 0.06, P < 0.001). Furthermore, a positive interaction between office systolic BP (SBP) and Acti-3%ODI for UACR was found (ß = 0.06, P < 0.001). Among the 6,568 persons enrolled in the analysis, 5,313 completed measurements of BP at home. In this cohort, the association of Acti-3%ODI with UACR remained significant (ß = 0.06, P < 0.001) even after morning and sleep SBP were included in the analysis. Furthermore, a mediation analysis revealed that 28.3% (95% confidence interval, 14.9-41.7%; P < 0.001) of the association of Acti-3%ODI with UACR was explained by the mediation of morning and sleep SBP metrics. Conclusions: SDB and office SBP were independently and synergistically associated with UAE, which is considered a risk factor for chronic kidney disease and cardiovascular events. SDB may raise UAE not only by increasing BP but also by involving other pathologic pathways.

Rates of Comorbidities in Very Low Birth Weight Infants Fed an Exclusive Human Milk Diet Versus a Bovine Supplemented Diet.

Background: Our level III neonatal intensive care unit (NICU) implemented the use of an exclusive human milk diet (EHD) and sought to determine its effect on the severe co-morbidities of preterm infants as well as the potential cost-savings due to the anticipated reduction in these co-morbidities. Methods: A retrospective cohort study was completed to determine if an EHD statistically decreased the rate of co-morbidities including length of stay (LOS), days on total parental nutrition (TPN), rates of late onset sepsis, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity (ROP). Results: An EHD significantly decreased the odds of severe ROP (adjusted odds-ratio (aOR)=0.349; 95%CI [0.156, 0.739]; p=0.008) and late onset sepsis (aOR=0.323; 95%CI [0.123, 0.768]; p=0.014). Analysis of cost-effectiveness of an EHD relative to a BSD based on the incremental costs of these co-morbidities determined the net loss in direct hospital costs per patient were estimated to be $420 in 2016 US dollars; however, given the long-term health-care costs and non-pecuniary damages from the co-morbidities of severe ROP and sepsis this net loss appears negligible. Conclusion: This study found that an EHD significantly decreased the odds of severe ROP and late onset sepsis; though not significant, there was a positive trend in decreasing cases of medical NEC; our surgical NEC rates dropped to 0. The benefits of human milk are vital, and the costs are nominal.

Effects of the COVID-19 lockdown on sleep duration in children and adolescents: A survey across different continents.

BACKGROUND: A parent survey was conducted to assess the sleep habits of children residing in various countries before and during the SARS-CoV-2 pandemic. It was hypothesized that lockdown would be associated with increased sleep duration. METHODS: Outcomes were changes in bedtime, wake time, and sleep duration in the pandemic compared to before. Logistic regression was applied to evaluate the effects of age and covariates on outcomes. RESULTS: A total of 845 questionnaires completed from May 1 to June 10, 2020 were analyzed (45.8% female; age 3-17 years). During the pandemic, 23.1% of preschoolers, 46.2% of school-age children, and 89.8% of adolescents were going to bed after 10 p.m. on weekdays compared to 7.1%, 9.4%, and 57.1% respectively before the pandemic, with these proportions being higher on weekends. Likewise, 42.5% of preschoolers, 61.3% of school-age children, and 81.2% of adolescents were waking after 8 a.m. on weekdays (11.6%, 4.9%, and 10.3%, before) with these proportions being greater on weekends. Sleep duration did not change in 43% of participants on weekdays and in 46.2% on weekends. The 14-17 years group had fourfold increased odds for longer sleep duration on weekdays (p < .01), and children aged 6-13 years had twofold increased odds for longer sleep duration on weekends relative to the 3-5 years age group (p = .01). CONCLUSIONS: Although lockdown was associated with later bedtime and wake time, this shift did not alter sleep duration in more than 40% of children. Yet, compared to preschoolers, high school-aged children were more likely to sleep more on weekdays and primary school children on weekends.

Skeletal muscle specific mitochondrial dysfunction and altered energy metabolism in a murine model (oim/oim) of severe osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder with patients exhibiting bone fragility and muscle weakness. The synergistic biochemical and biomechanical relationship between bone and muscle is a critical potential therapeutic target, such that muscle weakness should not be ignored. Previous studies demonstrated mitochondrial dysfunction in the skeletal muscle of oim/oim mice, which model a severe human type III OI. Here, we further characterize this mitochondrial dysfunction and evaluate several parameters of whole body and skeletal muscle metabolism. We demonstrate reduced mitochondrial respiration in female gastrocnemius muscle, but not in liver or heart mitochondria, suggesting that mitochondrial dysfunction is not global in the oim/oim mouse. Myosin heavy chain fiber type distributions were altered in the oim/oim soleus muscle with a decrease (-33 to 50%) in type I myofibers and an increase (+31%) in type IIa myofibers relative to their wildtype (WT) littermates. Additionally, altered body composition and increased energy expenditure were observed oim/oim mice relative to WT littermates. These results suggest that skeletal muscle mitochondrial dysfunction is linked to whole body metabolic alterations and to skeletal muscle weakness in the oim/oim mouse.

The Flu Vaccination May Have a Protective Effect on the Course of COVID-19 in the Pediatric Population: When Does Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Meet Influenza?

Background In the midst of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a lot more chaos could be anticipated in the flu season due to the coexistence of SARS-CoV-2 and influenza with almost similar epidemiologic and clinical features. Could this become a "twindemic" or "syndemic" if there is any viral interference occurs? We investigated the effect of influenza and pneumococcal vaccines on the disease course of SARS-CoV-2 in the pediatric population and the possibility of viral interference. Material and methods After approval from Institutional Review Board, a retrospective electronic chart review on 20 years and younger SARS-CoV-2 polymerase chain reaction (PCR) positive patients who visited Arkansas Children's Hospital System between February 1 to August 30, 2020, was performed. The clinical data was collected along with influenza and pneumococcal vaccination status of these patients. Results The results showed that viral interference may have played a role in the current flu and coronavirus disease 2019 (COVID-19) twindemic. SARS-CoV-2 and influenza may have significantly affected each other's epidemiological features. Conclusion Understanding the relationship and co-existence of other viruses alongside SARS-CoV-2 and knowing the vaccination status of the host population may help in deploying the right strategies to get the best outcomes.