Comparison of Caregiver- and Child-Reported Quality of Life in Children With Sleep-Disordered Breathing

Objective. Caregivers frequently report poor quality of life(QOL) in children with sleep-disordered breathing (SDB).Our objective is to assess the correlation between care-giver- and child-reported QOL in children with mild SDBand identify factors associated with differences between caregiver and child report. Study Design. Analysis of baseline data from a multi-institutional randomized trialSetting. Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index\3) were randomized to observation or adenotonsillectomy. Methods. The Pediatric Quality of Life Inventory (Peds QL)assessed baseline global QOL in participating children 5 to12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report. Results. Peds QL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQLscore was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P \ .001). The agreement between caregiver and child total Peds QL scores was poor, with intraclass correlation coefficients of 0.03 (95%CI, –0.09 to 0.15) for children 5 to 7 years old and 0.21(95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report. Conclusion. Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics

Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma.Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered.Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations.Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice.Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence. </p

The mothers, Omega-3 and mental health study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD.</p> <p>Methods/Design</p> <p>The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat.</p> <p>Discussion</p> <p>This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk.</p> <p>Trial registration</p> <p>Clinical trial registration number: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981877">NCT00711971</a></p

Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance

Geography, generalisability, and susceptibility in clinical trials

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The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma

Increased Expression of RhoA in Epithelium and Smooth Muscle of Obese Mouse Models: Implications for Isoprenoid Control of Airway Smooth Muscle and Fibroblasts

The simultaneous rise in the prevalence of asthma and obesity has prompted epidemiologic studies that establish obesity as a risk factor for asthma. The alterations in cell signaling that explain this link are not well understood and warrant investigation so that therapies that target this asthma phenotype can be developed. We identified a significant increase in expression of the small GTPase RhoA in nasal epithelial cells and tracheal smooth muscle cells from leptin-deficient (ob/ob) mice compared to their wild-type counterparts. Since RhoA function is dependent on isoprenoid modification, we sought to determine the role of isoprenoid-mediated signaling in regulating the viability and proliferation of human airway smooth muscle cells (ASM) and normal human lung fibroblasts (NHLF). Inhibiting isoprenoid signaling with mevastatin significantly decreased the viability of ASM and NHLF. This inhibition was reversed by geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP), suggesting specificity to the Rho GTPases. Conversely, increasing isoprenoid synthesis significantly increased ASM proliferation and RhoA protein expression. RhoA expression is inherently increased in airway tissue from ob/ob mice, and obesity-entrained alterations in this pathway may make it a novel therapeutic target for treating airway disease in the obese population

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study

Guilbert TW, Murphy KR, Hamelmann E, et al. Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study. Journal of Asthma and Allergy . 2024;17:81-87.Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils >= 150 cells/mu L or fractional exhaled nitric oxide >= 20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (>= 5% or >= 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV(1)) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV(1) to Week 12. Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of >= 5% in ppFEV(1); 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV(1) >= 10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P= 5%. Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV(1), with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV(1) response at Week 12

Improving Surveillance and Epidemic Response in Ohio Childcare Settings

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021. Additionally, active surveillance with self-administered reverse transcriptase&ndash;polymerase chain reaction (RT-PCR) tests were conducted among staff at 46 childcare programs. Finally, six zoom-based focus groups with program administrators were used to gain feedback. Staff and children in childcare settings contributed 0.38% and 0.15% of the COVID-19 cases in Ohio during this timeframe, respectively. RT-PCR testing identified 3 unrecognized cases (0.88% of tests), and all occurred when the statewide positivity rate was &gt;5%. Focus groups revealed that access to affordable cleaning supplies, masks, and reliable staffing were critical. Perhaps most importantly, we conclude that expanding the incident reporting system to include a childcare census would allow for the tracking of future health problems with highly valuable incidence rate estimations

Dupilumab improves lung function responder rates in children with type 2 asthma in the VOYAGE study

Guilbert T, Fiocchi AG, Murphy KR, et al. Dupilumab improves lung function responder rates in children with type 2 asthma in the VOYAGE study. In: ERS International Congress 2023 abstracts. European Respiratory Journal. Vol 62. Sheffield: European Respiratory Society; 2023.Introduction: Persistent lung function impairment in children with asthma is associated with impaired quality of life and risk of exacerbation. In phase 3 LIBERTY ASTHMA VOYAGE (NCT02948959), add-on dupilumab (DPL) was generally well tolerated and significantly reduced the annualized rate of severe exacerbations (AER) and improved lung function in children. Aims and objectives: To evaluate lung function responder rates at Week (Wk)12 and Wk52 of VOYAGE. Methods: Children 6–11 years with uncontrolled, moderate-to-severe, type 2 asthma (baseline [BL] blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) were randomized to dupilumab 100mg/200mg (based on bodyweight) q2w or volume-matched placebo for 52 wks. Endpoints: least squares mean (LSM) change from BL in % predicted pre-BD FEV1 (ppFEV1) at Wk12 and 52; proportion of patients with ≥10% improvement in ppFEV1 at Wk12 and 52; and AER in those responders. Results: ppFEV1 was significantly improved with DPL vs placebo (PBO) at Wk12 (LSM difference [95% CI] 5.20 [2.14–8.26]; P= 0.0009) and Wk52 (7.79 [4.36–11.22]; P<0.0001). A ≥10% ppFEV1 improvement was achieved at Wk12 in 44.9% (n=106; [38.5–51.5]) vs 31.6% (n=36; [23.2–40.9]; P=0.0173) and at Wk52 in 47.5% (n=112; [40.9–54.0]) vs 28.1% (n=32; [20.1–37.3]; P=0.0006) of patients receiving DPL vs PBO, respectively. DPL vs PBO significantly decreased the AER in patients achieving ≥10% ppFEV1 improvement, 0.304 (n=106; [0.185–0.500]) vs 0.744 (n=36; [0.424–1.308]; P=0.0103), respectively