Exploring Heterogeneity in Cost-Effectiveness Using Machine Learning Methods: A Case Study Using the FIRST-ABC Trial.

OBJECTIVE: The aim of this study was to explore heterogeneity in the cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with continuous positive airway pressure (CPAP) in children following extubation. DESIGN: Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the individual and subgroup levels using a causal forest approach, alongside a seemingly unrelated regression (SUR) approach for comparison. SETTINGS: FIRST-ABC is a noninferiority randomized controlled trial (ISRCTN60048867) including children in UK paediatric intensive care units, which compared HFNC with CPAP as the first-line mode of noninvasive respiratory support. PATIENTS: In the step-down FIRST-ABC, 600 children clinically assessed to require noninvasive respiratory support were randomly assigned to HFNC and CPAP groups with 1:1 treatment allocation ratio. In this analysis, 118 patients were excluded because they did not consent to accessing their medical records, did not consent to follow-up questionnaire or did not receive respiratory support. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study is the incremental net monetary benefit (INB) of HFNC compared with CPAP using a willingness-to-pay threshold of £20,000 per QALY gain. INB is calculated based on total costs and quality adjusted life years (QALYs) at 6 months. The findings suggest modest heterogeneity in cost-effectiveness of HFNC compared with CPAP at the subgroup level, while greater heterogeneity is detected at the individual level. CONCLUSIONS: The estimated overall INB of HFNC is smaller than the INB for patients with better baseline status suggesting that HFNC can be more cost-effective among less severely ill patients.

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Management of obstructive sleep apnoea in primary care.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in the community and is increasing in prevalence. Primary care plays a pivotal role in the diagnosis and management of OSA. OBJECTIVE: This article focuses on the management options for a patient with an established diagnosis of OSA and provides a guide for driving licensing requirements. Indications for continuous positive airway pressure (CPAP) are discussed and tips provided to consider when conducting a review appointment, including trouble shooting. DISCUSSION: There are several treatment options available for patients with an established diagnosis of OSA. Selecting the optimal therapy involves aligning the symptoms and severity of OSA with the presence of comorbidities. CPAP is a highly effective therapy for symptomatic adults with moderate-to-severe OSA and for some symptomatic patients with mild OSA. Early trouble shooting of side effects and using supportive interventions increases the probability of long-term adherence, which is key to symptomatic improvement.

Management of neonates with respiratory distress syndrome in resource-limited settings.

In South Africa, prematurity stands as one of the foremost causes of neonatal mortality. A significant proportion of these deaths occur because of respiratory distress syndrome of prematurity. The implementation of non-invasive respiratory support, such as continuous positive airway pressure (CPAP), has demonstrated both safety and efficacy in reducing mortality rates and decreasing the need for mechanical ventilation. Given the absence of blood gas analysers and limited radiological services in many district hospitals, the severity of respiratory distress is often assessed through observation of the infant's work of breathing and the utilisation of bedside scoring systems. Based on the work of breathing, non-invasive therapy can be commenced timeously. While evidence supporting the use of high-flow nasal cannula as a primary treatment for respiratory distress syndrome remains limited, it may be considered as an alternative, provided that CPAP machines are available. The purpose of this article is to advocate the use of non-invasive therapy in low resource-limited settings and describe the indications, contraindications, complications, and application of CPAP therapy. This would benefit healthcare workers, especially in low-care settings and district hospitals.

Combination Therapies with an Oral Appliance in the Management of Obstructive Sleep Apnea.

Combination therapy (CT) with a mandibular advancement device (MAD) and positive airway pressure (PAP) has been advocated for patients for whom neither MAD nor PAP alone provides an efficacious and tolerated therapy. This article reviews the small and limited, but growing body of evidence in support of CT and highlights details in its implementation. In most studies, CT was found to be preferred by many, but not all PAP-intolerant patients. CT can be more efficacious than either MAD or PAP alone.

Surfactant administration methods for premature newborns: LISA vs. INSURE comparative analysis.

INTRODUCTION: Respiratory Distress Syndrome (RDS) is the most common respiratory disorder among premature infants. The use of surfactant has significantly reduced respiratory complications and mortality. There are two conventional methods for administering surfactant: Intubate-Surfactant-Extubate (INSURE) and Less Invasive Surfactant Administration (LISA). This study aims to compare the effects of surfactant administration using these two methods on the treatment outcomes of premature newborns. MATERIALS AND METHODS: In this retrospective cohort study, we included 100 premature newborns with RDS and spontaneous breathing who were admitted to the Neonatal Intensive Care Unit of Besat Hospital in Sanandaj city in 2021. Exclusion criteria comprised congenital anomalies and the needing for intubation for resuscitation at birth. The outcomes of epmericaly trated with two methods were compared: the LISA (50 neonates) and the INSURE (50 neonates). Our interesting outcomes were needing for mechanical ventilation, duration of ventilation, pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia. Finally, we entered the data into STATA-14 statistical software and analyzed it using chi-square and t-tests. RESULTS: In this study, 69% of the neonates were boys. The LISA group exhibited significantly lower rates of need for mechanical ventilation (P = 0.003) and ventilation duration (P < 0.001) compared to the INSURE group. Conversely, there were no significant differences between the two groups (P > 0.05) in terms of pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia rates. CONCLUSION: The results of this study suggest that the LISA method is a safe and non-invasive approach for surfactant administration. Notably, it resulted in a reduced need for mechanical ventilation and decreased ventilation duration compared to the INSURE method.

Understanding adherence to continuous positive airway pressure in patients with obstructive sleep apnea post-stroke: A prospective study based on the Andersen model.

Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) post-stroke is often problematic, despite potential benefits. This study aimed to evaluate CPAP adherence in patients with OSA post-stroke based on the Andersen behavioral model of health services utilization. A total of 227 eligible participants were recruited from a Chinese hospital. After baseline assessment, participants were followed for 6 months to determine short-term CPAP adherence. Those with good short-term adherence were followed for an additional 6 months to explore long-term adherence and influencing factors. Short-term CPAP adherence rate was 33%. Being married or living with a partner, having an associate degree or baccalaureate degree or higher, and stronger health beliefs independently predicted short-term CPAP adherence. Only 25% of participants from the adherent group showed good long-term adherence. The factor associated with long-term CPAP adherence was participants not using alcohol. Adherence to CPAP is suboptimal among patients having OSA post-stroke. Addressing unfavorable predisposing factors and modifying health beliefs are suggested.

Sleep Apnea and Heart Failure-Current State-of-The-Art.

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.

Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial.

BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.

Role of Sleep-Disordered Breathing and Epicardial Connections in the Recurrence of Atrial Fibrillation.

The presence of epicardial connections (ECs) between the pulmonary veins (PVs) and atrium may contribute to atrial fibrillation (AF) recurrence. This study aimed to determine the impact of sleep-disordered breathing (SDB) on the presence of ECs and the interplay between SDB and ECs on AF recurrence.We retrospectively reviewed 400 consecutive non-valvular AF patients. Among them, 235 patients exhibiting a 3% oxygen desaturation index (ODI) of ≥ 10 events/hour underwent polysomnography to evaluate the SDB severity, measured by the apnea-hypopnea index (AHI). To facilitate the ablation of AF and ECs, a high-density mapping catheter (HDMC) was employed. AF recurrence was evaluated over a 12-month period post-AF ablation.The key findings included: 1) 63% of AF patients with ECs had SDB with an AHI ≥ 20 events/hour. 2) Despite achieving complete PV isolations and precise EC ablation using an HDMC, SDB presence was associated with an increased AF recurrence. 3) Continuous positive airway pressure therapy for SDB improved AF recurrence among the AF patients with both ECs and SDB (57% versus 73%; P = 0.016). 4) AHI (odds ratio [OR] = 1.91, ≥ 28.4 events/hour) and left atrial volume (LAV) (OR = 1.42, ≥ 128.3 mL) were independent predictors of the presence of ECs, and AHI (OR = 1.44, ≥ 27.8 events/hour) was an independent predictor of the presence of AF recurrence.It is essential for physicians to recognise the potential complexity of ECs and SDB in AF patients. Thus, screening and treating SDB in AF patients presenting with ECs might play a pivotal role in suppressing AF recurrence.

Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Obstructive Sleep Apnea Effects on Chronic Airway Disease Exacerbations-Missed Opportunities for Improving Outcomes in Chronic Obstructive Pulmonary Disease and Asthma.

In patients with chronic obstructive pulmonary disease (COPD) and asthma, exacerbations determine the natural history of both diseases. Patients with both respiratory diseases who suffer from obstructive sleep apnea (OSA) as a comorbidity (overlap syndromes) have a higher risk of exacerbations and hospitalization. In cases of OSA/COPD and OSA/asthma, continuous positive airway pressure treatment is indicated. Adequate adherence to therapy appears to reduce exacerbations and their severity, especially in OSA/COPD overlap. However, there is a lack of randomized trials that definitively demonstrate this evidence.

Targeting Hypercapnia in Chronic Lung Disease and Obesity Hypoventilation: Benefits and Challenges.

Hypoventilation is a complication that is not uncommon in chronic obstructive pulmonary disease and calls for both medical treatment of the underlying disease and, frequently, noninvasive ventilation either during exacerbations requiring hospitalization or in a chronic state in the patient at home. Obesity hypoventilation syndrome by definition is associated with ventilatory failure and hypercapnia. It may or may not be accompanied by obstructive sleep apnea, which when detected becomes an additional target for positive airway pressure treatment. Intensive research has not completely resolved the best choice of treatment, and the simplest modality, continuous positive airway pressure, may still be entertained.

Asthma and obstructive sleep apnea: Unveiling correlations and treatable traits for comprehensive care.

Asthma and obstructive sleep apnea (OSA) are common respiratory disorders. They share characteristics such as airway obstruction, poor sleep quality, and low quality of life. They are often present as comorbidities, along with obesity, gastroesophageal reflux disease (GERD), and allergic rhinitis (AR), which impacts the disease's control. In recent years, there has been discussion about the association between these conditions and their pathophysiological and clinical consequences, resulting in worse health outcomes, increased healthcare resource consumption, prolonged hospital stays, and increased morbidity and mortality. Some studies demonstrate that treatment with continuous positive airway pressure (CPAP) can have a beneficial effect on both pathologies. This review summarizes the existing evidence of the association between asthma and OSA at their pathophysiological, epidemiological, clinical, and therapeutic levels. It intends to raise awareness among healthcare professionals about these conditions and the need for further research.

Chronic Cough and Obstructive Sleep Apnea.

Chronic cough, defined as a cough lasting more than 8 weeks, is a common medical condition occurring in 5% to 10% of the population. Its overlap with another highly prevalent disorder, obstructive sleep apnea (OSA), is therefore not surprising. The relationship between chronic cough and OSA extends beyond this overlap with higher prevalence of OSA in patients with chronic cough than in the general population. The use of continuous positive airway pressure can result in improvement in chronic cough although further studies are needed to understand which patients will experience benefit in their cough from the treatment of comorbid OSA.

Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.

Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2 / Relationship between obstructive sleep apnea and type 2 diabetes mellitus

Introducción: La asociación entre la apnea obstructiva del sueño (AOS) y el metabolismo de la glucosa sigue siendo controvertida. Este estudio investiga la relación entre la AOS y la diabetes mellitus tipo 2 (DM) y prediabetes (preDM) incidentes, así como el efecto del tratamiento con presión positiva continua en la vía aérea (CPAP) a largo plazo. Métodos: Estudio de seguimiento en cohorte retrospectiva clínica de pacientes con AOS y controles seleccionados de manera aleatoria. Los datos sobre DM incidente y preDM, así como de la CPAP se obtuvieron de los registros hospitalarios. La relación entre AOS basal y la DM incidente se examinó con modelos de regresión de Cox. Resultados: De un total de 356 pacientes, 169 con AOS y 187 controles fueron seguidos por una mediana de 98 meses; 47 enfermos (13,2%) desarrollaron DM y 43 (12,1%) preDM. La incidencia acumulada a los cinco años de DM fue de 10,7% (6,5-13,9%). De los sujetos con preDM en la muestra basal, 87% evolucionaron a DM incidente. Se demuestra que el índice de masa corporal (IMC), la hipoxia nocturna y el índice de apnea hipopnea (IAH) son factores de riesgo para el desarrollo de DM, y que la CPAP los disminuye. Conclusiones: Los pacientes con AOS tienen mayor probabilidad de desarrollar DM. Los factores de riesgo implicados son el IMC, la hipoxia nocturna y el IAH. El uso regular de CPAP a largo plazo se asoció con una disminución de estos. (AU)

Introduction: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. Methods: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. Results: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5–13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. Conclusions: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk. (AU)