Annals of the American Thoracic Society最新文献

Rationale: Although the mainstay of sepsis treatment is timely initiation of broad-spectrum antimicrobials, treatment delays are common, especially among patients who develop hospital-onset sepsis. The time of day has been associated with suboptimal clinical care in several contexts, but its association with treatment initiation among patients with hospital-onset sepsis is unknown. Objectives: Assess the association of time of day with antimicrobial initiation among ward patients with hospital-onset sepsis. Methods: This retrospective cohort study included ward patients who developed hospital-onset sepsis while admitted to five acute care hospitals in a single health system from July 2017 through December 2019. Hospital-onset sepsis was defined by the Centers for Disease Control and Prevention Adult Sepsis Event criteria. We estimated the association between the hour of day and antimicrobial initiation among patients with hospital-onset sepsis using a discrete-time time-to-event model, accounting for time elapsed from sepsis onset. In a secondary analysis, we fit a quantile regression model to estimate the association between the hour of day of sepsis onset and time to antimicrobial initiation. Results: Among 1,672 patients with hospital-onset sepsis, the probability of antimicrobial initiation at any given hour varied nearly fivefold throughout the day, ranging from 3.0% (95% confidence interval [CI], 1.8-4.1%) at 7 a.m. to 13.9% (95% CI, 11.3-16.5%) at 6 p.m., with nadirs at 7 a.m. and 7 p.m. and progressive decline throughout the night shift (13.4% [95% CI, 10.7-16.0%] at 9 p.m. to 3.2% [95% CI, 2.0-4.0] at 6 a.m.). The standardized predicted median time to antimicrobial initiation was 3.2 hours (interquartile range [IQR], 2.5-3.8 h) for sepsis onset during the day shift (7 a.m.-7 p.m.) and 12.9 hours (IQR, 10.9-14.9 h) during the night shift (7 p.m.-7 a.m.). Conclusions: The probability of antimicrobial initiation among patients with new hospital-onset sepsis declined at shift changes and overnight. Time to antimicrobial initiation for patients with sepsis onset overnight was four times longer than for patients with onset during the day. These findings indicate that time of day is associated with important care processes for ward patients with hospital-onset sepsis. Future work should validate these findings in other settings and elucidate underlying mechanisms to inform quality-enhancing interventions.

Rationale: The diagnostic yield of traditional ultrasound-guided pleural biopsy remains unsatisfactory, particularly when the pleural thickness is ⩽5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography (UE) has a better diagnostic yield than traditional ultrasound for malignant pleural effusion (MPE). However, studies on UE-guided pleural biopsies are lacking. Objectives: To evaluate the feasibility and safety of UE-guided pleural biopsy. Methods: In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness was ⩽5 mm with no pleural nodules were enrolled between July 2019 and August 2021. The diagnostic yield of UE-guided pleural biopsy for pleural effusion and its sensitivity for detecting MPE were evaluated. Results: Ninety-eight patients (mean age, 62.4 ± 13.2 yr; 65 men) were prospectively enrolled. The diagnostic yield of UE-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and its sensitivity for MPE was 88.7% (55/62). In addition, its sensitivity for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax. Conclusions: UE-guided pleural biopsy is a novel technique for diagnosing MPE with good diagnostic yield and sensitivity. Clinical trial registered with https://www.chictr.org.cn (ChiCTR2000033572).

Rationale: Cystic fibrosis (CF) is a genetic disease leading to progressive lung function loss and early mortality. Many clinical and demographic variables are associated with lung function decline, but little is known about the effects of prolonged periods of missed care. Objectives: To determine if missed care in the Cystic Fibrosis Foundation Patient Registry (CFFPR) is associated with decreased lung function at follow-up visits. Methods: Deidentified CFFPR data for 2004-2016 were analyzed, with the exposure of interest being ⩾12-month gap in CFFPR data. We modeled percentage predicted forced expiratory volume in 1 second using longitudinal semiparametric modeling with natural cubic splines for age (knots at quantiles) and with subject-specific random effects, adjusted for sex and CFTR (cystic fibrosis transmembrane conductance regulator) genotype, race, and ethnicity and included time-varying covariates for gaps in care, insurance type, underweight body mass index, CF-related diabetes status, and chronic infections. Results: A total of 24,328 individuals with 1,082,899 encounters in the CFFPR met inclusion criteria. In the cohort, 8,413 (35%) individuals had at least a single ⩾12-month episode of discontinuity, whereas 15,915 (65%) had continuous care. Of the encounters preceded by a 12-month gap, 75.8% occurred in patients 18 years and older. Compared with those with continuous care, those with a discontinuous care episode had a lower follow-up percentage predicted forced expiratory volume in 1 second at the index visit (-0.81%; 95% confidence interval, -1.00, -0.61) after adjustment for other variables. The magnitude of this difference was much greater (-2.1%; 95% confidence interval, -1.5, -2.7) in young adult F508del homozygotes. Conclusions: There was a high rate of ⩾12-month gap in care, especially in adults, documented in the CFFPR. Discontinuous care identified in the CFFPR was strongly associated with decreased lung function, especially in adolescents and young adults homozygous for the F508del CFTR mutation. This may have implications for identifying and treating people with lengthy gaps in care and may have implications for CFF care recommendations.

Rationale: Sarcoidosis is a racially disparate granulomatous disease likely caused by environmental exposures, genes, and their interactions. Despite increased risk in African Americans, few environmental risk factor studies in this susceptible population exist. Objectives: To identify environmental exposures associated with the risk of sarcoidosis in African Americans and those that differ in effect by self-identified race and genetic ancestry. Methods: The study sample comprised 2,096 African Americans (1,205 with and 891 without sarcoidosis) compiled from three component studies. Unsupervised clustering and multiple correspondence analyses were used to identify underlying clusters of environmental exposures. Mixed-effects logistic regression was used to evaluate the association of these exposure clusters and the 51 single-component exposures with risk of sarcoidosis. A comparison case-control sample of 762 European Americans (388 with and 374 without sarcoidosis) was used to assess heterogeneity in exposure risk by race. Results: Seven exposure clusters were identified, five of which were associated with risk. The exposure cluster with the strongest risk association was composed of metals (P < 0.001), and within this cluster, exposure to aluminum had the highest risk (odds ratio, 3.30; 95% confidence interval [95% CI], 2.23-4.09; P < 0.001). This effect also differed by race (P < 0.001), with European Americans having no significant association with exposure (odds ratio, 0.86; 95% CI, 0.56-1.33). Within African Americans, the increased risk was dependent on genetic African ancestry (P = 0.047). Conclusions: Our findings support African Americans having sarcoidosis environmental exposure risk profiles that differ from those of European Americans. These differences may underlie racially disparate incidence rates that are partially explained by genetic variation differing by African ancestry.

Rationale: Limited information exists about the epidemiology, outcomes, and predictors of weaning from mechanical ventilation in patients with spinal cord injury. Objectives: Our aim was to investigate predictors of weaning outcomes for patients with traumatic spinal cord injury (tSCI) and develop and validate a prognostic model and score for weaning success. Methods: This was a registry-based, multicentric cohort study including all adult patients with tSCI requiring mechanical ventilation (MV) and admitted to one of the intensive care units (ICUs) of the Trauma Registry at St. Michael's Hospital (Toronto, ON, Canada) and the Canadian Rick Hansen Spinal Cord Injury Registry between 2005 and 2019. The primary outcome was weaning success from MV at ICU discharge. Secondary outcomes included weaning success at Days 14 and 28, time to liberation from MV accounting for competing risk of death, and ventilator-free days at 28 and 60 days. Associations between baseline characteristics and weaning success or time to liberation from MV were measured using multivariable logistic and competing risk regressions. A parsimonious model to predict weaning success and ICU discharge was developed and validated via bootstrap. A prediction score for weaning success at ICU discharge was derived, and its discriminative ability was assessed using receiver operating characteristic curve analysis and compared with the Injury Severity Score (ISS). Results: Of 459 patients analyzed, 246 (53.6%), 302 (65.8%), and 331 (72.1%) were alive and free of MV at Day 14, Day 28, and ICU discharge, respectively; 54 (11.8%) died in the ICU. Median time to liberation from MV was 12 days. Factors associated with weaning success were Blunt injury (odds ratio [OR], 2.96; P = 0.010), ISS (OR, 0.98; P = 0.025), Complete syndrome (OR, 0.53; P = 0.009), age in Years (OR, 0.98; P = 0.003), and Cervical LEsion (OR, 0.60; P = 0.045). The BICYCLE score showed a greater area under the curve than the ISS (0.689 [95% confidence interval (CI), 0.631-0.743] vs. 0.537 [95% CI, 0.479-0.595]; P < 0.0001). Factors predicting weaning success also predicted time to liberation. Conclusions: In a large multicentric cohort, 72% of patients with tSCI were weaned and discharged alive from the ICU. Readily available admission characteristics can reasonably predict weaning success and help prognostication.

Rationale: Population-based data on the epidemiology of nontuberculosis mycobacterial (NTM) infections are limited, particularly with respect to variation in NTM infection among racial groups and socioeconomic strata. Wisconsin is one of a handful of states where mycobacterial disease is notifiable, allowing large, population-based analyses of the epidemiology of NTM infection in this state. Objectives: To estimate the incidence of NTM infection in Wisconsin adults, describe the geographic distribution of NTM infection across the state, identify the frequency and type of infection caused by different NTM species, and investigate associations between NTM infection and demographics and socioeconomic status. Methods: We conducted a retrospective cohort study using laboratory reports of all NTM isolates from Wisconsin residents submitted to the Wisconsin Electronic Disease Surveillance System from 2011 to 2018. For the analyses of NTM frequency, multiple reports from the same individual were enumerated as separate isolates when nonidentical, collected from different sites or collected more than one year apart. Results: A total of 8,135 NTM isolates from 6,811 adults were analyzed. Mycobacterium avium complex accounted for 76.4% of respiratory isolates. The M. chelonae-abscessus group was the most common species isolated from skin and soft tissue. The annual incidence of NTM infection was stable over the study period (from 22.1 per 100,000 to 22.4 per 100,000). The cumulative incidence of NTM infection among Black (224 per 100,000) and Asian (244 per 100,000) individuals was significantly higher compared with that among their White counterparts (97 per 100,000). Total NTM infections were significantly more frequent (P < 0.001) in individuals from disadvantaged neighborhoods, and racial disparities in the incidence of NTM infection generally remained consistent when stratified by measures of neighborhood disadvantage. Conclusions: More than 90% of NTM infections were from respiratory sites, with the vast majority caused by M. avium complex. Rapidly growing mycobacteria predominated as skin and soft tissue pathogens and were important minor respiratory pathogens. We found a stable annual incidence of NTM infection in Wisconsin between 2011 and 2018. NTM infection occurred more frequently in non-White racial groups and in individuals experiencing social disadvantage, suggesting that NTM disease may be more frequent in these groups as well.

Rationale: Poor adherence limits the effectiveness of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). A better understanding of CPAP adherence is needed to develop novel strategies to improve it. Objectives: To determine if the chronotype (morning, evening, or intermediate) of patients with OSA is associated with differences in CPAP adherence. If such an association exists, determine the mechanisms underlying this association. Methods: We performed a secondary analysis of the APPLES (Apnea Positive Pressure Long-term Efficacy Study) clinical trial. We assessed chronotype using the Morningness-Eveningness Questionnaire (MEQ) among participants randomized to the CPAP arm with daily adherence data (n = 469). Evening (MEQ ⩽ 41), intermediate (41 < MEQ < 59), and morning type (MEQ ⩾ 59) categories were the exposures. We modeled daily CPAP use (hours per night) over a 6-month period, using a linear mixed model, adjusted for covariates (e.g., age, sex, marital status). To assess mechanisms of the association, we performed mediation analyses using sleep duration, weekend catch-up sleep, depression, and other factors. Results: Most participants were obese men with severe OSA (body mass index of 32.3 ± 7.3 kg/m², 65% male, and apnea-hypopnea index 39.8 ± 24.6/h). Participants were 44% morning, 47% intermediate, and 8% evening chronotype. Participants with the morning chronotype reported the shortest sleep duration on weekends (7.3 vs. 7.6 and 7.9 h/night) compared with the intermediate and evening types. Participants with the morning chronotype exhibited a 40-min/night higher CPAP use (P = 0.001) than persons with the intermediate chronotype. This relationship was mildly attenuated (32.8 min/night; P = 0.011) after adjustment for covariates. None of the selected factors (e.g., sleep duration, weekend catch-up sleep) exhibited a significant mediation effect. Conclusions: Morning chronotype is associated with a clinically meaningful increase in CPAP adherence compared with other chronotypes. Mechanisms of this association require further study. Chronotype may be a novel predictor of CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT00051363).