Intrapleural tissue plasminogen activator (tPA) plus deoxyribonuclease (DNase) improves drainage in pleural infection, but the optimal administration sequence is uncertain. We evaluated whether concurrent co-instillation of tPA/DNase is associated with improved effectiveness or altered safety compared with sequential administration in patients with infectious pleural effusions. We performed a retrospective cohort study at a tertiary hospital in Southern California including adults who received intrapleural tPA and DNase (August 2017-August 2025). We restricted our analysis to suspected or confirmed infectious pleural effusions. Exposure was concurrent co-instillation (single dwell) versus sequential administration (tPA followed 1 hour later by DNase with separate dwells). Primary outcomes were radiographic resolution on follow-up chest CT as documented in contemporaneous radiology reports, need for surgical intervention (VATS/open decortication), and hospital length of stay. Multivariable logistic regression adjusted for age, sex, body mass index, chest tube size, early therapy initiation (<24 hours from chest tube placement), and chest tube placement method. Safety endpoints included analgesic utilization (from medication administration records) and serial hemoglobin trends and transfusion. Among 233 treated patients, 210 met criteria for infectious pleural effusions (sequential n = 149; concurrent n = 61). Radiographic resolution occurred more frequently with concurrent versus sequential therapy (80% vs 52%) and remained independently associated with concurrent administration after adjustment (adjusted OR 4.70, 95% CI 2.18-10.10). Surgical intervention occurred in 25% overall and was less frequent with concurrent therapy (13% vs 30%); concurrent administration was associated with lower adjusted odds of surgery (adjusted OR 0.30, 95% CI 0.13-0.70). Median length of stay was 10 days (IQR 7-15) with concurrent therapy versus 12 days (IQR 9-16) with sequential therapy (P = .059). Analgesic utilization during therapy did not differ meaningfully between strategies. Hemoglobin trajectories and transfusion rates were similar, and transfusion during therapy was rare. In this single-center cohort of infectious pleural effusions, concurrent intrapleural tPA/DNase administration was associated with higher radiographic resolution and lower surgical referral compared with sequential dosing, without evidence of increased analgesic burden or bleeding-related safety signals. Prospective comparative studies are warranted to confirm causality and identify patients most likely to benefit.

Black and Hispanic people with CF (PwCF) experience worse health outcomes related to pulmonary disease compared to White, non-Hispanic PwCF. Improving outcomes in minoritized PwCF is a crucial need in the CF community, but prior evidence suggests that these communities are underrepresented in CF clinical research. To determine whether CF clinical studies are representative of the overall CF population. The study cohort included participants from recent cystic fibrosis transmembrane conductance regulator modulator studies (CHEC-SC, PROMISE, PROSPECT, and GOAL). Persons seen at the same centers who were eligible for these studies based on inclusion and exclusion criteria, but who did not enroll in these studies were used as a comparator cohort from the CFF Patient Registry (CFFPR). Rates of study enrollment were assessed separately for Black race and Hispanic ethnicity versus non-Hispanic White PwCF. Propensity weighted Poisson regression models were used to account for potential confounders in the relationship between race and study participation. Demographic characteristics were compared between 3,594 PwCF in the four modulator studies with 14,888 individuals from the CFFPR who were eligible, but did not enroll. Enrollees were younger (median age 19 years), more likely to have had at least three clinic visits per year, and live within 30 miles of the study site. Black and Hispanic PwCF were less likely to have private insurance and less likely to live far from study centers. Multivariable analysis revealed that Black individuals were significantly less likely than non-Hispanic White individuals to enroll in CHEC-SC and PROMISE, with a 17% and 32% lower likelihood, respectively. Hispanic individuals had a 34% lower enrollment rate than non-Hispanic White individuals in PROMISE but higher enrollment in PROSPECT. Differences in enrollment rates were greater at sites with fewer minority participants. These results suggest that Black and Hispanic PwCF are, overall, significantly less likely to be included in CF clinical research than non-Hispanic White PwCF. Future research is needed to better understand if these differences are upheld in studies with varying inclusion/exclusion criteria and clinical sites.

Multiple studies have shown that symptom-based subtypes of obstructive sleep apnea (OSA) exist and are generalizable to clinical and population-based samples of different race/ethnic and regional backgrounds. However, there have not been studies evaluating the generalizability within a clinical sample of Chinese ancestry. Thus, the aim of the current study was to investigate the generalizability of symptom-based subtypes within clinical patients from China. This is a cross-sectional, multi-center study of patients with OSA from international sleep centers participating in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Two Chinese cohorts were collected: 666 patients from Peking University People's Hospital (PKUPH) and 503 patients from other China sites (Peking University International Hospital, Taiwan, and Shanghai). In addition, 694 White patients were included from 7 sites across 5 countries (Iceland, Germany [Berlin], Australia [Sydney, Perth], Brazil, and the United States [Ohio State University and University of Pennsylvania]). Symptom-based subtypes were determined using a latent class analysis (LCA) of 18 self-reported symptom variables and 3 comorbidities. A total of 1,863 patients were included in the LCA. The previously described 5 symptom subtype (disturbed sleep, minimal symptoms, excessively sleepy, moderately sleepy, and upper airway symptoms dominant) were optimal in the PKUPH site, other China sites, and White patients from SAGIC. Chinese patients had higher prevalence of the minimal symptoms subtype (P < .001) compared to White patients. Among the five subtypes, the excessively sleepy subtype exhibited the highest AHI, and ODI. : Based on the included symptoms and comorbidities, five subtypes provided the optimal groupings across both Chinese and White patients in SAGIC. Chinese patients were more likely to present with fewer symptoms. These data further enhance understanding of the generalizability of OSA symptom subtypes across ethnically diverse backgrounds, and pave the way for precision management of OSA in the future.

Quetiapine is commonly prescribed "off-label" to people with insomnia symptoms. People with undiagnosed obstructive sleep apnea (OSA) frequently report insomnia symptoms, particularly difficulties maintaining sleep. In 2023, 10.7 million prescriptions were dispensed for quetiapine in the United States. Yet, there is limited information regarding the effects of quetiapine on sleep, breathing, and next-day performance in people with OSA. To determine the effects of 50 mg of quetiapine versus placebo on OSA severity and other polysomnographic parameters plus next day vigilance and driving simulator performance in people with OSA who also reported difficulty maintaining sleep. We performed a double-blind, randomized, placebo-controlled, cross-over study (NCT05303935) in 15 people with OSA and difficulty maintaining sleep. Participants were studied overnight via polysomnography twice ∼1 week apart and received either 50 mg of quetiapine or placebo (order randomized) just prior to sleep. A 10-minute psychomotor vigilance task (PVT) and 30-minute driving simulator test were performed each morning. Compared to placebo, quetiapine reduced the apnea/hypopnea index (primary outcome) ([Mean ± SD] 27 ± 16 vs. 20 ± 12 events/h, P = .009), arousal index (32 ± 16 vs. 25 ± 9 arousals/h, P = .012), and increased sleep efficiency (80 ± 11 vs. 87 ± 9%, P < .001) without worsening hypoxemia (mean overnight SpO2 94.7 ± 1.2 vs. 94.5 ± 1.5%, P = .38). However, next morning vigilance (median PVT reaction time 336 ± 48 vs. 382 ± 84 ms, P = .008) and driving simulator performance (steering deviation 72 ± 38 vs. 96 ± 53 cm, P < .01) were significantly impaired with quetiapine. Consistent with a hypnotic effect, a single night of low-dose quetiapine reduced OSA severity as measured via the apnea/hypopnea index and increased sleep efficiency without worsening overnight hypoxemia. However, there was evidence of next day impairment in vigilance and driving simulator performance. NCT05303935. National Health and Medical Research Council of Australia (1196261).

The exclusion of Spanish-speaking participants in psychobehavioral trials among critical illness survivors limits the generalizability of evidence-based interventions. However, adapting interventions for inclusivity is challenging and few examples exist in the field for replication. To describe the cultural and linguistic adaptation of the Blueprint mobile app-based adaptive coping skills intervention to Spanish for inclusion in a multicenter trial, its usability testing, and lessons learned from the process. A multidisciplinary team of native English and Spanish speakers conducted an iterative three-step adaptation. Step 1 involved an initial cultural and linguistic adaptation of key scripted content of an existing psychobehavioral intervention for critical illness survivors ("Blueprint") to Spanish by a group that included community members, members of a Latino-serving health advocacy group, and clinicians. In Step 2, bilingual trial network members created final versions of all text and images, which were then professionally produced for an equivalent Spanish language version of the Blueprint mobile application. Step 3 involved a formal usability test of the final Spanish version among bilingual participants (n = 10) by comparing observed to target values of the Systems Usability Scale (SUS). The team successfully developed adaptations of 35 elements of audio, video, and text content. The mean SUS score of 83.1 (10.7 SD) exceeded our a priori usability target of 80. Key lessons learned included that translation software is inadequate to comprehensively incorporate cultural norms, diverse dialect representation is essential, extensive time and expense is required, and consensus must be balanced against cost and time constraints. We conducted a successful cultural and linguistic adaptation of an English language psychobehavioral intervention to a highly usable Latin American Spanish version using a methodologically rigorous process. Lessons learned from this project can assist researchers seeking to increase the number of Spanish language psychobehavioral interventions and the generalizability of future trials.

Advanced polysomnographic (PSG) metrics reflecting the physiological causes and consequences of sleep apnea may enable precision medicine in research settings, but their feasibility in routine clinical practice has yet to be demonstrated. Assess (1) the generalizability of PSG metrics from research to clinical cohort, and (2) their associations with a broad range of comorbid diseases, many of which have not been previously examined. PSG metrics including endotypes (eg, loop gain) and physiological burdens (eg, hypoxic burden) were estimated from diagnostic polysomnographs of 6,427 participants at Mass General Brigham (MGB; Boston, MA). Comorbid conditions analyzed from MGB's medical record system included 9 representative cardio-metabolic and respiratory diseases, as well as 408 prevalent diseases. Associations were assessed using modified Poisson and LASSO regression. The sample included 62% females, age: 52.9 ± 16.8 years, and apnea-hypopnea index (AHI) 21.4 ± 15.9 events/hr. Associations between endotypes and demographics/obesity-related factors were consistent with prior observational studies (median difference in β = 0.03SD). After adjusting for AHI, older age was associated with lower heart rate (-0.40SD) and arousal burdens (-0.23SD), while higher BMI was associated with increased hypoxic burden (0.25SD). Having demonstrated that there is reasonable concordance with published data, our subsequent analysis identified distinct and clinically meaningful associations between advanced PSG metrics and comorbid conditions. Specifically, elevated loop gain, ventilatory burden, and hypoxic burden were associated with hypertension, diabetes, and renal failure; increased ventilatory instability was associated with cardiovascular disease; and reduced collapsibility and ventilatory instability with chronic airway obstruction. Even after LASSO-based selection, no single PSG metric consistently predicted risk across all comorbidities; ventilatory instability showed the most associations among endotypic traits, and heart rate burden among physiological burdens, underscoring the heterogeneity of OSA pathophysiology. Phenome-wide analyses of a large clinical cohort demonstrate the real-world feasibility and clinical relevance of extracting advanced PSG metrics, supporting their potential to identify personalized, mechanism-specific intervention targets for sleep apnea.

Recent randomized controlled trials failed to show cardiovascular benefits of treating obstructive sleep apnea (OSA) in intention-to-treat analyses which has been a matter of debate since publication of the results. To address whether untreated OSA persists after one year in adults with coronary artery disease (CAD) following revascularization and to explore whether major cardiovascular and cerebrovascular events (MACCEs) differ between the patients who persist vs improve in OSA severity. The study population included 119 CAD patients with moderate to severe OSA from the RICCADSA trial. All participants had an apnea-hypopnea index (AHI) ≥ 15/h and were randomized to no continuous positive airway pressure (CPAP) therapy (n = 81) or were not using the device (n = 38). Patients without OSA (AHI < 5/h) at baseline (n = 85) were included as a control group. Home sleep apnea tests were performed at baseline and after one year. The median AHI decreased from 24.5 (19.4-36.0/h) to 15.1 (8.2-27.3/h) and Oxygen Desaturation Index (4%) decreased from 14.8 (7.3-22.9/h) to 6.6/h (2.7-14.4/h) after one year (P < .001 for both). In all, 73 (61.3%) improved in OSA severity (59 had AHI 5-14.9/h and 14 had AHI < 5/h) whereas 46 (38.7%) had persistent OSA. The control group had a median AHI 4.4 (2.9-7.9/h) after one year. N-Terminal Pro-B-Type Natriuretic Peptide values decreased significantly in the overall cohort, with similar directional trends across OSA trajectory groups. The patients with improvement in OSA had significantly lower risk for MACCEs (Hazard Ratio 0.25, %95 CI 0.08-0.76; P = .015) compared to the patients with persistent OSA. Most of the CAD patients with moderate to severe OSA improve in OSA severity one year after revascularization, probably due to the improved cardiac function, and have a decreased risk for MACCEs compared to individuals with persistent OSA. Identifying patients with persistent OSA after revascularization may help target those most likely to benefit from focused intervention, particularly in settings where CPAP therapy is not initiated or is poorly tolerated.