Evaluating pharmacological treatments for excessive daytime sleepiness in obstructive sleep apnea: A comprehensive network meta-analysis and systematic review.

Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS). Pharmacotherapy offers a potential treatment approach for EDS in OSA patients. This systematic review and meta-analysis aimed to assess the efficacy and safety of pharmacological interventions for alleviating EDS in patients with OSA. Following PRISMA guidelines, we included randomized controlled trials investigating pharmacological treatments for EDS in adult OSA until August 2023. We conducted meta-analysis, subgroup, and meta-regression analyses using a random effects model. Finally, a network meta-analysis synthesized direct and indirect evidence, followed by a comprehensive safety analysis. We included 32 articles in the meta-analysis (n = 3357). Pharmacotherapy showed a significant improvement in the Epworth Sleepiness Scale (ESS) score (Mean Difference (MD) -2.73, (95 % Confidence Interval (CI) [-3.25, -2.20], p < 0.01) and Maintenance of Wakefulness Test (MWT) score (MD 6.00 (95 % CI [2.66, 9.33] p < 0.01). Solriamfetol, followed by Pitolisant and modafinil, exhibited the greatest ESS reduction, while Danavorexton, followed by Solriamfetol and MK-7288, had the strongest impact on MWT. MK-7288 had the most total adverse events (AEs), followed by Danavorexton and armodafinil. Pharmacological Interventions significantly alleviate EDS in OSA patients but with heterogeneity across medications. Treatment decisions should involve a personalized assessment of patient factors and desired outcomes.

Pneumatic stenting in the surgical candidacy assessment for cough variant expiratory central airway collapse.

Expiratory Central Airway Collapse (ECAC) is a multifactorial, underdiagnosed entity that poses unique challenges. Airway stenting is used as a predictor for successful outcomes after central airway stabilization surgery via tracheobronchoplasty (TBP). This approach may pose suboptimal performance in certain ECAC variants. We hypothesize that Continuous Positive Airway Pressure (CPAP), used as a pneumatic stent, could be a non-invasive alternative to evaluate surgical candidacy in cough-predominant ECAC presentations. We report on a 67-year-old female with a history of chronic cough and confirmed ECAC. After optimization of medical therapy without significant relief and unsuccessful stent trial. We opted to perform CPAP trial during exercise, the patient exercised on a treadmill, and CPAP was applied at two levels (9 cmH2O, 11 cmH2O). The use of CPAP was associated with resolution of cough and a decrease in exercise-related perceived exertion. Applying CPAP during exercise may be a promising alternative to stent trials to determine patients' candidacy for surgical management of cough-predominant ECAC.

A prospective, comparative trial of standard and breath-actuated nebulizer: efficacy, safety, and satisfaction.

BACKGROUND: Nebulized drug delivery is a cornerstone of therapy for obstructive lung disease, but the ideal nebulizer design is uncertain. The breath-actuated nebulizer (BAN) may be superior to conventional nebulizers. This study compared the BAN to standard nebulizer with regard to efficacy, safety, and patient and respiratory therapist (RT) satisfaction. METHODS: Adults admitted to the hospital and for whom nebulizer therapy was prescribed were enrolled. Subjects were randomly assigned to either AeroEclipse II or standard nebulizer and were surveyed at the completion of each treatment. BAN delivered albuterol 2.5 mg or albuterol 2.5 mg plus ipratropium 0.25 mg. Standard nebulizer delivered albuterol 2.5 mg or albuterol plus ipratropium 0.5 mg. An RT assessed each subject's heart rate, respiratory rate, and peak expiratory flow rate prior to and following treatment. Treatment time and adverse events were recorded. Each RT was asked to assess his/her satisfaction with each of the nebulizers. RESULTS: Twenty-eight subjects were studied. The mean age was 69 years. Fifty-four percent of the subjects indicated that overall the BAN was superior to conventional nebulizer therapy; 68% indicated that duration was preferable with the BAN. RTs were more satisfied with the BAN, based on overall performance, treatment duration, and ease of use. There were no significant differences in heart rate, peak expiratory flow rate, or respiratory rate before or after nebulization therapy with either device. The duration of treatment was significantly lower with the BAN (4.1 min vs 9.9 min, P < .001). Additionally, the BAN was associated with a lower occurrence of adverse events. CONCLUSIONS: Patients and RTs expressed greater satisfaction with the BAN, compared with standard nebulizer. Pre- and post-treatment vital signs did not differ between groups, but use of the BAN was associated with a shorter duration and a lower occurrence of adverse events. Taken together, these data support the use of the BAN for nebulized medication delivery.

A comparison of 2 visual methods for classifying obstructive vs central hypopneas.

STUDY OBJECTIVES: Rules for classifying apneas as obstructive, central, or mixed are well established. Although hypopneas are given equal weight when calculating the apnea-hypopnea index, classification is not standardized. Visual methods for classifying hypopneas have been proposed by the American Academy of Sleep Medicine and by Randerath et al (Sleep. 2013;36[3]:363-368) but never compared. We evaluated the clinical suitability of the 2 visual methods for classifying hypopneas as central or obstructive. METHODS: Fifty hypopnea-containing polysomnographic segments were selected from patients with clear obstructive or clear central physiology to serve as standard obstructive or central hypopneas. These 100 hypopnea-containing polysomnographic segments were deidentified, randomized, and scored by 2 groups. We assigned 1 group to use the American Academy of Sleep Medicine criteria and the other the Randerath algorithm. After a washout period, re-randomized hypopnea-containing polysomnographic segments were scored using the alternative method. We determined the accuracy (agreement with standard), interrater (Fleiss's κ), and intrarater agreement (Cohen's κ) for obtained scores. RESULTS: Accuracy of the 2 methods was similar: 67% vs 69.3% for Randerath et al and the American Academy of Sleep Medicine, respectively. Cohen's κ was 0.01-0.75, showing that some raters scored similarly using the 2 methods, while others scored them markedly differently. Fleiss's κ for the American Academy of Sleep Medicine algorithm was 0.32 (95% confidence interval, 0.29-0.36) and for the Randerath algorithm was 0.27 (95% confidence interval, 0.23-0.30). CONCLUSIONS: More work is needed to discover a noninvasive way to accurately characterize hypopneas. Studies like ours may lay the foundation for discovering the full spectrum of physiologic consequences of obstructive sleep apnea and central sleep apnea.

Occult lymph node metastasis in radiologic stage I non-small cell lung cancer: The role of endobronchial ultrasound.

RATIONALE: The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is currently recommended for staging non-small cell lung cancer (NSCLC) in centrally located tumors, tumors >3 cm, or with radiologic evidence of lymph node (LN) metastasis. Current guidelines do not recommend staging EBUS-TBNA in patients with stage I NSCLC who do not have any of the aforementioned conditions. OBJECTIVE: We hypothesize that using EBUS-TBNA is useful for detecting occult metastasis in radiologic stage I NSCLC. METHODS: In this single-center, retrospective study, charts of patients ≥18 years old who underwent staging EBUS-TBNA from January 2005 to May 2019 were reviewed. Only patients with combined positron-emission tomography and computed tomography (PET/CT) scans consistent with radiologic stage I NSCLC were included. Identified variables included: age, gender, personal history of any cancer, smoking history, tumor location, tumor centrality, tumor size, tumor PET activity, histopathologic type of NSCLC, and LN biopsy results. Patients whose LN samples showed a diagnosis other than NSCLC were excluded. The association between LN positivity, and each of the variables was assessed using Pearson's correlation for categorical variables, and logistic regression analysis for continuous variables. RESULTS: From the 2,892 initially screened patients, 188 were included. Of those, 13 (6.9%; 95% CI, 4%-11%) had a malignancy-positive LN biopsy. The number needed to test (NNT) in order to detect one case of any occult metastasis was 15. Among the included variables, a significant association was found between LN positivity and tumor centrality, with central tumors found in 61.5% of patients with positive LN (n = 8) (p < 0.01). This association stayed significant after adjusting for age, gender, smoking history, tumor size, tumor location, and PET activity (p = 0.015). Among patients with malignancy-positive LN biopsies, five (38.5%; 95% CI, 17.6%-64.6%) were upstaged to N1, and eight (61.5%; 95% CI, 35.4%-82.4%) were upstaged to N2, with NNT of 23 to detect one case of occult N2 metastasis. Subgroup analysis comparing LN-positive patients based on their N stage did not show statistically significant association with any of the variables. CONCLUSION: Based on our results and along with the existing evidence, EBUS-TBNA should be recommended as part of the routine staging in all patients with radiologic stage I NSCLC.

Prevalence of restless legs syndrome in blood donors.

Iron deficiency anemia has been linked to restless legs syndrome (RLS) and regular blood donation may lead to iron deficiency. It has been reported that blood donations may be associated with RLS. A recent study from Sweden found that 25% of the women donors were affected by RLS. However, this type of study has not been replicated in the United States. We conducted a study in our blood donation unit between September and October 2008. To identify those with RLS, we used the RLS diagnostic index questionnaire by Benes et al. The proportion of blood donors with RLS was estimated and the number of blood donations and hemoglobin levels were compared according to RLS status. One hundred and fifty one patients were interviewed; 7 patients who donated only platelets were excluded, leaving 144 patients for analysis. There were 13 (9.0%, 95% confidence interval [CI]: 4.9-14.9%) patients with RLS. Of these, 7 (4.9%, 95% CI: 2.0-9.8%) had possible RLS and 6 (4.2%, 95% CI: 1.5-8.9%) had major or clinically relevant RLS. There was no dramatic association between RLS and number of blood donations or hemoglobin level (all P >or= 0.21). In our sample of blood donors in the United States, the prevalence of major RLS was 4%. We could not demonstrate an association between RLS and the frequency of blood donation or hemoglobin level in our relatively small sample; a larger sample is needed to better identify any associations.

Prevalence of acute vasoresponsiveness in patients with pulmonary hypertension: treatment implications.

OBJECTIVE: Pulmonary hypertension (PH) is a serious and often progressive disorder that results in right ventricular dysfunction. The general reported rate of patients who are responders is 10%-26%. More recently, using the current criteria, the rate of acute vasodilator response was as low as 6%. This study used the most current guidelines to assess the prevalence of acute vasoresponsiveness in patients with PH. METHODS: A retrospective chart review of 618 patients seen in the PH clinic at the Mayo Clinic Jacksonville from 1991 to June 2008 was conducted. We assessed the prevalence of acute vasoresponsiveness in patients with PH who had undergone vasodilator trial with epoprostenol or nitric oxide, using the current accepted criteria. RESULTS: One hundred and seventy-six patients who underwent a vasodilator trial that had complete hemodynamic data were identified. The average age was 61 +/- 14 years and most were women (67%). The PH was severe with most patients in the World Health Organization (WHO) functional class III-IV (82%), and an average mean pulmonary artery pressure of 48 +/- 11 mm Hg. Although the study group included all WHO diagnostic groups, 69% were diagnosed as Group I pulmonary arterial hypertension. We found an overall prevalence of response to acute vasodilator therapy to be 26%. CONCLUSION: Using the most current criteria to identify acute responders to vasodilator therapy in PH patients, we found a slightly higher rate of "responders" than previously reported. Acute vasodilator testing identifies a clinically important group who may benefit from calcium channel blockers (CCBs), and this study confirms that a significant percentage of PH patients are acutely vasoresponsive.

Catamenial pneumothorax with umbilical and diaphragmatic endometriosis: a case report and review of the literature.

A 44-year-old female presented with a history of recurrent right-sided pneumothoraces, uterine fibroids, and a palpable lump in her navel. Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and resection of the umbilical nodule was performed. Intraoperative inspection of the right hemidiaphragm revealed adherent brownish-blue nodules without any associated diaphragmatic defects and a similar-appearing nodule at the umbilicus. She had no symptoms of pelvic endometriosis, nor did surgical exploration reveal any. Her postoperative course was uneventful and she denied recurrent pneumothorax at 12-month followup. Recurrent pneumothoraces in women of a reproductive age should raise the suspicion of thoracic endometriosis. Failure to establish the diagnosis prevents appropriate curative interventions.

Disseminated Mycobacterium interjectum Infection with Bacteremia, Hepatic and Pulmonary Involvement Associated with a Long-Term Catheter Infection.

We present a 49-year-old female with one year of intermittent fevers, chills, night sweats, and significant weight loss. Liver and lung biopsy showed evidence of a granulomatous process. Blood and liver biopsy cultures yielded growth of presumed Mycobacterium interjectum, thought to be related to a disseminated long-term central venous catheter infection. She successfully received one year of combined antimicrobial therapy after catheter removal without recurrence of disease. M. interjectum has been previously described as a cause of lymphadenitis in healthy children and associated with pulmonary disease in adults, although other localized infections have been reported. This is the first case described of a disseminated M. interjectum infection with bacteremia, hepatic and pulmonary involvement associated with a long-term catheter infection.

Survey of restless legs syndrome in a pulmonary hypertension population.

INTRODUCTION: The prevalence of restless legs syndrome (RLS) varies from 5% to 24% in the general population and is associated with a variety of medical disorders. However, the association between RLS and pulmonary hypertension (PH) is unknown. OBJECTIVES: To determine the prevalence of RLS in PH patients. METHODS: A cross-sectional questionnaire was given to patients with PH who attended the Pulmonary Hypertension Association conference. We used the RLS Diagnostic Index questionnaire. Demographic data included age, gender, height, weight, body mass index (BMI), medication list, PH World Health Organization (WHO) diagnosis group and current WHO functional class. RESULTS: The study included 128 PH patients. Most were females (86.8%) with a mean age of 49.68 years [standard deviation (SD) 14.24]. The mean BMI was 31.3 (SD 20.46). One hundred and twenty-one patients (93.75%) were classified as WHO group 1 (pulmonary arterial hypertension). Three patients were identified in WHO group 3 (hypoxemic states), four patients in group 4 (chronic thromboemboli) and one patient in group 5 (2.3%, 3.1% and 0.8%, respectively). Definite RLS was found in 16 of 128 patients with PH resulting in a prevalence of 12.5%, possible RLS in 39 of 128 patients (30.46%) and no RLS in 73 (57.03%) patients. CONCLUSION: The prevalence of RLS is not increased in PH. There is a high prevalence of possible RLS in our study. The overall prevalence of combined definite and possible RLS is significant. Future research is needed to assess more patients with PH and the association or correlation with RLS.

Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension.

INTRODUCTION: A reduced diffusing capacity of the lung for carbon monoxide (DLCO) measured during a pulmonary function test can suggest pulmonary arterial hypertension (PAH). The DLCO has been reported to weakly correlate with pulmonary hemodynamics. OBJECTIVE: To determine whether the relationship between the DLCO and pulmonary arterial pressures can be strengthened by normalizing the DLCO to spirometric variables. PATIENT AND METHODS: Patients were seen at a tertiary care referral center. Consecutive subjects who underwent right heart catheterization (RHC) for the evaluation of suspected PAH from 01 January 1991 through 01 October 2006 were identified. Pulmonary function testing (PFT) data performed within 60 days of the RHC was collected. Spearman rank correlation between PFT and RHC variables was calculated. RESULTS: One hundred thirty-eight patients who had an RHC performed had complete PFTs available. No significant correlation was identified between the mean pulmonary artery pressure and the pulmonary vascular resistance against the DLCO, nor the DLCO when normalized to: forced expiratory volume in 1 s, forced vital capacity, total lung capacity or alveolar volume. Spirometric subgroups were identified by standard definitions of restrictive and/or obstructive ventilatory defects. Clinical subgroups were classified based on the clinically diagnosed cause of the patient's PAH. Again, no significant correlation was identified between the PFT variables and RHC measurements in these stratified subgroups. CONCLUSION: In patients with suspected PAH, invasive hemodynamic measurements of PAH do not correlate with PFT variables, even when corrected for spirometric volumes, and regardless of the subgroup of ventilatory physiology or clinical diagnosis.

Utility of d-dimer in the diagnosis of patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of severe pulmonary hypertension (PH). D-dimer, a degradation product of fibrin, has been used as a marker for various diseases. In patients with idiopathic pulmonary arterial hypertension there is evidence to suggest that D-dimer levels are associated with disease severity; however, data regarding D-dimer in patients with CTEPH are lacking. OBJECTIVE: To assess the significance of D-dimer in patients with CTEPH. PATIENTS AND METHODS: Retrospective chart review of 618 patients seen at our PH clinic from 1991 to June 2008. Data collection focused on patients diagnosed with CTEPH, D-dimer levels, demographics, clinical, and hemodynamics. We compared D-dimer levels in CTEPH patients or World Health Organization (WHO) diagnostic group 4 with PH patients in WHO group 1. RESULTS: Thirty-four patients with confirmed CTEPH were identified, of these 19 had D-dimer levels and 7 were positive. Of the 234 patients in WHO group 1 excluding patients with portopulmonary hypertension (n = 54) and pulmonary venoocclusive disease (n = 2) 97 had D-dimer levels and 52 were positive. We found an estimated sensitivity of the D-dimer test in diagnosing CTEPH was 37% while the estimated specificity was 46%. The positive predictive value and negative predictive value were 12% and 79% respectively. CONCLUSION: D-dimer is an insensitive and nonspecific test for the diagnosis of CTEPH. Despite a high negative predictive value D-dimer alone cannot be used to rule out CTEPH in patients with PH.