Identifying Patterns of Medical Intervention in Acute Respiratory Failure: A Retrospective Observational Study

IMPORTANCE:. Characterizing medical interventions delivered to ICU patients over time and their relationship to outcomes can help set expectations and inform decisions made by patients, clinicians, and health systems. OBJECTIVES:. To determine whether distinct and clinically relevant pathways of medical intervention can be identified among adult ICU patients with acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS:. Retrospective observational study using all-payer administrative claims data from 2012 to 2014. Patients were identified from the Healthcare Cost and Utilization Project State Inpatient Databases from Maryland, Massachusetts, Nevada, and Washington. MAIN OUTCOMES AND MEASURES:. Patterns of cumulative medical intervention delivery, over time, using temporal k-means clustering of interventions delivered up to hospital days 0, 5, 10, 20, and up to discharge. RESULTS:. A total of 12,175 admissions were identified and divided into training (75%; n = 9,130) and validation sets (25%; n = 3,045). Without applying a priori classification and using only medical interventions to cluster, we identified three distinct pathways of intervention accounting for 93.5% of training set admissions. We found 45.9% of admissions followed a “cardiac” intervention pathway (e.g., cardiac catheterization, cardioversion); 36.7% followed a “general” pathway (e.g., diagnostic interventions); and 17.4% followed a “prolonged” pathway (e.g., tracheostomy, gastrostomy). Prolonged pathway admissions had longer median hospital length of stay (13 d; interquartile range [IQR], 7.5–18.5 d) compared with cardiac (5; IQR, 2.5–7.5) and general (5; IQR, 3–7). In-hospital death occurred in 24.6% of prolonged pathway admissions compared with 17.9% of cardiac and 6.9% of general. Findings were confirmed in the validation set. CONCLUSIONS AND RELEVANCE:. Most ICU admissions for acute respiratory failure follow one of three clinically relevant pathways of medical intervention which are associated with hospitalization outcomes. This study helps define the longitudinal nature of critical care delivery, which can inform efforts to predict patient outcomes, communicate with patients and their families, and organize critical care resources

High-quality genetic mapping with ddRADseq in the non-model tree Quercus rubra

Abstract Background Restriction site associated DNA sequencing (RADseq) has the potential to be a broadly applicable, low-cost approach for high-quality genetic linkage mapping in forest trees lacking a reference genome. The statistical inference of linear order must be as accurate as possible for the correct ordering of sequence scaffolds and contigs to chromosomal locations. Accurate maps also facilitate the discovery of chromosome segments containing allelic variants conferring resistance to the biotic and abiotic stresses that threaten forest trees worldwide. We used ddRADseq for genetic mapping in the tree Quercus rubra, with an approach optimized to produce a high-quality map. Our study design also enabled us to model the results we would have obtained with less depth of coverage. Results Our sequencing design produced a high sequencing depth in the parents (248×) and a moderate sequencing depth (15×) in the progeny. The digital normalization method of generating a de novo reference and the SAMtools SNP variant caller yielded the most SNP calls (78,725). The major drivers of map inflation were multiple SNPs located within the same sequence (77% of SNPs called). The highest quality map was generated with a low level of missing data (5%) and a genome-wide threshold of 0.025 for deviation from Mendelian expectation. The final map included 849 SNP markers (1.8% of the 78,725 SNPs called). Downsampling the individual FASTQ files to model lower depth of coverage revealed that sequencing the progeny using 96 samples per lane would have yielded too few SNP markers to generate a map, even if we had sequenced the parents at depth 248×. Conclusions The ddRADseq technology produced enough high-quality SNP markers to make a moderately dense, high-quality map. The success of this project was due to high depth of coverage of the parents, moderate depth of coverage of the progeny, a good framework map, an optimized bioinformatics pipeline, and rigorous premapping filters. The ddRADseq approach is useful for the construction of high-quality genetic maps in organisms lacking a reference genome if the parents and progeny are sequenced at sufficient depth. Technical improvements in reduced representation sequencing (RRS) approaches are needed to reduce the amount of missing data

Interhospital Transfer of Patients With Acute Respiratory Failure in the United States: A Scoping Review

OBJECTIVES:. Interhospital transfer of patients with acute respiratory failure (ARF) is relevant in the current landscape of critical care delivery. However, current transfer practices for patients with ARF are highly variable, poorly formalized, and lack evidence. We aim to synthesize the existing evidence, identify knowledge gaps, and highlight persisting questions related to interhospital transfer of patients with ARF. DATA SOURCES:. Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, CINAHL Plus, and American Psychological Association. STUDY SELECTION:. We included studies that evaluated or described hospital transfers of adult (age > 18) patients with ARF between January 2020 and 2024 conducted in the United States. Using predetermined search terms and strategies, a total of 3369 articles were found across all databases. After deduplication, 1748 abstracts were screened by authors with 45 articles that advanced to full-text review. This yielded 16 studies that fit our inclusion criteria. DATA EXTRACTION:. The studies were reviewed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews by three authors. DATA SYNTHESIS:. Included studies were mostly retrospective analyses of heterogeneous patients with various etiologies and severity of ARF. Overall, transferred patients were younger, had high severity of illness, and were more likely to have commercial insurance compared with nontransferred cohorts. There is a paucity of data examining why patients get transferred. Studies that retrospectively evaluated outcomes between transferred and nontransferred cohorts found no differences in mortality, although transferred patients have a longer length of stay. There is limited evidence to suggest that patients transferred early in their course have improved outcomes. CONCLUSIONS:. Our scoping review highlights the sparse evidence and the urgent need for further research into understanding the complexity behind ARF transfers. Future studies should focus on defining best practices to inform clinical decision-making and improve downstream outcomes

Defining the Time-limited Trial for Patients with Critical Illness: An Official American Thoracic Society Workshop Report.

In critical care, the specific, structured approach to patient care known as a time-limited trial has been promoted in the literature to help patients, surrogate decision makers, and clinicians navigate consequential decisions about life-sustaining therapy in the face of uncertainty. Despite promotion of the time-limited trial approach, a lack of consensus about its definition and essential elements prevents optimal clinical use and rigorous evaluation of its impact. The objectives of this American Thoracic Society Workshop Committee were to establish a consensus definition of a time-limited trial in critical care, identify the essential elements for conducting a time-limited trial, and prioritize directions for future work. We achieved these objectives through a structured search of the literature, a modified Delphi process with 100 interdisciplinary and interprofessional stakeholders, and iterative committee discussions. We conclude that a time-limited trial for patients with critical illness is a collaborative plan among clinicians and a patient and/or their surrogate decision makers to use life-sustaining therapy for a defined duration, after which the patients response to therapy informs the decision to continue care directed toward recovery, transition to care focused exclusively on comfort, or extend the trials duration. The plans 16 essential elements follow four sequential phases: consider, plan, support, and reassess. We acknowledge considerable gaps in evidence about the impact of time-limited trials and highlight a concern that if inadequately implemented, time-limited trials may perpetuate unintended harm. Future work is needed to better implement this defined, specific approach to care in practice through a person-centered equity lens and to evaluate its impact on patients, surrogates, and clinicians

Timing of Intubation in Coronavirus Disease 2019: A Study of Ventilator Mechanics, Imaging, Findings, and Outcomes

Objectives:. Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design:. Retrospective cohort study. Setting:. Northwestern Memorial Hospital ICUs. Patients:. All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions:. Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results:. Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions:. The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation

Obesity, inflammatory and thrombotic markers, and major clinical outcomes in critically ill patients with COVID‐19 in the US

Objective This study aimed to determine whether obesity is independently associated with major adverse clinical outcomes and inflammatory and thrombotic markers in critically ill patients with COVID‐19. Methods The primary outcome was in‐hospital mortality in adults with COVID‐19 admitted to intensive care units across the US. Secondary outcomes were acute respiratory distress syndrome (ARDS), acute kidney injury requiring renal replacement therapy (AKI‐RRT), thrombotic events, and seven blood markers of inflammation and thrombosis. Unadjusted and multivariable‐adjusted models were used. Results Among the 4,908 study patients, mean (SD) age was 60.9 (14.7) years, 3,095 (62.8%) were male, and 2,552 (52.0%) had obesity. In multivariable models, BMI was not associated with mortality. Higher BMI beginning at 25 kg/m2 was associated with a greater risk of ARDS and AKI‐RRT but not thrombosis. There was no clinically significant association between BMI and inflammatory or thrombotic markers. Conclusions In critically ill patients with COVID‐19, higher BMI was not associated with death or thrombotic events but was associated with a greater risk of ARDS and AKI‐RRT. The lack of an association between BMI and circulating biomarkers calls into question the paradigm that obesity contributes to poor outcomes in critically ill patients with COVID‐19 by upregulating systemic inflammatory and prothrombotic pathways