Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality.

OBJECTIVE: A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). METHODS: Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs. RESULTS: In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively. CONCLUSION: Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD.

Sepsis and acute respiratory failure in patients with cancer: how can we improve care and outcomes even further?

PURPOSE OF REVIEW: Care and outcomes of critically ill patients with cancer have improved over the past decade. This selective review will discuss recent updates in sepsis and acute respiratory failure among patients with cancer, with particular focus on important opportunities to improve outcomes further through attention to phenotyping, predictive analytics, and improved outcome measures. RECENT FINDINGS: The prevalence of cancer diagnoses in intensive care units (ICUs) is nontrivial and increasing. Sepsis and acute respiratory failure remain the most common critical illness syndromes affecting these patients, although other complications are also frequent. Recent research in oncologic sepsis has described outcome variation - including ICU, hospital, and 28-day mortality - across different types of cancer (e.g., solid vs. hematologic malignancies) and different sepsis definitions (e.g., Sepsis-3 vs. prior definitions). Research in acute respiratory failure in oncology patients has highlighted continued uncertainty in the value of diagnostic bronchoscopy for some patients and in the optimal respiratory support strategy. For both of these syndromes, specific challenges include multifactorial heterogeneity (e.g. in etiology and/or underlying cancer), delayed recognition of clinical deterioration, and complex outcomes measurement. SUMMARY: Improving outcomes in oncologic critical care requires attention to the heterogeneity of cancer diagnoses, timely recognition and management of critical illness, and defining appropriate ICU outcomes.

Clinician Perspectives on Barriers and Enablers to Implementing an Inpatient Oncology Early Warning System: A Mixed-Methods Study.

PURPOSE: To elicit end-user and stakeholder perceptions regarding design and implementation of an inpatient clinical deterioration early warning system (EWS) for oncology patients to better fit routine clinical practices and enhance clinical impact. METHODS: In an explanatory-sequential mixed-methods study, we evaluated a stakeholder-informed oncology early warning system (OncEWS) using surveys and semistructured interviews. Stakeholders were physicians, advanced practice providers (APPs), and nurses. For qualitative data, we used grounded theory and thematic content analysis via the constant comparative method to identify determinants of OncEWS implementation. RESULTS: Survey respondents generally agreed that an oncology-focused EWS could add value beyond clinical judgment, with nurses endorsing this notion significantly more strongly than other clinicians (nurse: median 5 on a 6-point scale [6 = strongly agree], interquartile range 4-5; doctors/advanced practice providers: 4 [4-5]; P = .005). However, some respondents would not trust an EWS to identify risk accurately (n = 36 [42%] somewhat or very concerned), while others were concerned that institutional culture would not embrace such an EWS (n = 17 [28%]).Interviews highlighted important aspects of the EWS and the local context that might facilitate implementation, including (1) a model tailored to the subtleties of oncology patients, (2) transparent model information, and (3) nursing-centric workflows. Interviewees raised the importance of sepsis as a common and high-risk deterioration syndrome. CONCLUSION: Stakeholders prioritized maximizing the degree to which the OncEWS is understandable, informative, actionable, and workflow-complementary, and perceived these factors to be key for translation into clinical benefit.

Use of Inhaled Epoprostenol in Patients With COVID-19 Receiving Humidified, High-Flow Nasal Oxygen Is Associated With Progressive Respiratory Failure.

BACKGROUND: The clinical benefit of using inhaled epoprostenol (iEpo) through a humidified high-flow nasal cannula (HHFNC) remains unknown for patients with COVID-19. RESEARCH QUESTION: Can iEpo prevent respiratory deterioration for patients with positive SARS-CoV-2 findings receiving HHFNC? STUDY DESIGN AND METHODS: This multicenter retrospective cohort analysis included patients aged 18 years or older with COVID-19 pneumonia who required HHFNC treatment. Patients who received iEpo were propensity score matched to patients who did not receive iEpo. The primary outcome was time to mechanical ventilation or death without mechanical ventilation and was assessed using Kaplan-Meier curves and Cox proportional hazard ratios. The effects of residual confounding were assessed using a multilevel analysis, and a secondary analysis adjusted for outcome propensity also was performed in a multivariable model that included the entire (unmatched) patient cohort. RESULTS: Among 954 patients with positive SARS-CoV-2 findings receiving HHFNC therapy, 133 patients (13.9%) received iEpo. After propensity score matching, the median number of days until the composite outcome was similar between treatment groups (iEpo: 5.0 days [interquartile range, 2.0-10.0 days] vs no-iEpo: 6.5 days [interquartile range, 2.0-11.0 days]; P = .26), but patients who received iEpo were more likely to meet the composite outcome in the propensity score-matched, multilevel, and multivariable unmatched analyses (hazard ratio, 2.08 [95% CI, 1.73-2.50]; OR, 4.72 [95% CI, 3.01-7.41]; and OR, 1.35 [95% CI, 1.23-1.49]; respectively). INTERPRETATION: In patients with COVID-19 receiving HHFNC therapy, use of iEpo was associated with the need for invasive mechanical ventilation.

Prompting physicians to address a daily checklist and process of care and clinical outcomes: a single-site study.

RATIONALE: Checklists may reduce errors of omission for critically ill patients. OBJECTIVES: To determine whether prompting to use a checklist improves process of care and clinical outcomes. METHODS: We conducted a cohort study in the medical intensive care unit (MICU) of a tertiary care university hospital. Patients admitted to either of two independent MICU teams were included. Intervention team physicians were prompted to address six parameters from a daily rounding checklist if overlooked during morning work rounds. The second team (control) used the identical checklist without prompting. MEASUREMENTS AND MAIN RESULTS: One hundred and forty prompted group patients were compared with 125 control and 1,283 preintervention patients. Compared with control, prompting increased median ventilator-free duration, decreased empirical antibiotic and central venous catheter duration, and increased rates of deep vein thrombosis and stress ulcer prophylaxis. Prompted group patients had lower risk-adjusted ICU mortality compared with the control group (odds ratio, 0.36; 95% confidence interval, 0.13-0.96; P = 0.041) and lower hospital mortality compared with the control group (10.0 vs. 20.8%; P = 0.014), which remained significant after risk adjustment (odds ratio, 0.34; 95% confidence interval, 0.15-0.76; P = 0.008). Observed-to-predicted ICU length of stay was lower in the prompted group compared with control (0.59 vs. 0.87; P = 0.02). Checklist availability alone did not improve mortality or length of stay compared with preintervention patients. CONCLUSIONS: In this single-site, preliminary study, checklist-based prompting improved multiple processes of care, and may have improved mortality and length of stay, compared with a stand-alone checklist. The manner in which checklists are implemented is of great consequence in the care of critically ill patients.

Pulmonary Arterial Hypertension in Pregnancy.

Pulmonary arterial hypertension is a rare disease that predominantly affects women. The pathophysiology of the disease is complex, with both genetic and hormonal influences. Pregnancy causes significant physiologic changes that may not be well tolerated with underlying pulmonary arterial hypertension, in particular leading to volume overload and increased pulmonary pressures. A multidisciplinary approach and careful monitoring are essential for appropriate management of pulmonary arterial hypertension during pregnancy. Nonetheless, outcomes are still poor, and pregnancy is considered a contraindication in patients with pulmonary arterial hypertension.

Bloodstream Infections and Delayed Antibiotic Coverage Are Associated With Negative Hospital Outcomes in Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Bloodstream infections (BSIs) are common after hematopoietic stem cell transplantation (HSCT) and are associated with increased long-term morbidity and mortality. However, short-term outcomes related to BSI in this population remain unknown. More specifically, it is unclear whether choices related to empiric antimicrobials for potentially infected patients are associated with patient outcomes. RESEARCH QUESTION: Are potential delays in appropriate antibiotics associated with hospital outcomes among HSCT recipients with BSI? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study at a large comprehensive inpatient academic cancer center between January 2014 and June 2017. We identified all admissions for HSCT and prior recipients of HSCT. We defined potential delay in appropriate antibiotics as > 24 h between positive blood culture results and the initial dose of an antimicrobial with activity against the pathogen. RESULTS: We evaluated 2,751 hospital admissions from 1,086 patients. Of these admissions, 395 (14.4%) involved one or more BSIs. Of these 395 hospitalizations, 44 (11.1%) involved potential delays in appropriate antibiotics. The incidence of mortality was higher in BSI hospitalizations than in those without BSI (23% vs 4.5%; P < .001). In multivariable analysis, BSI was an independent predictor of mortality (OR, 8.14; 95% CI, 5.06-13.1; P < .001). Mortality was higher for admissions with potentially delayed appropriate antibiotics than for those with appropriate antibiotics (48% vs 20%; P < .001). Potential delay in antibiotics was also an independent predictor of mortality in multivariable analysis (OR, 13.8; 95% CI, 5.27-35.9; P < .001). INTERPRETATION: BSIs were common and independently associated with increased morbidity and mortality. Delays in administration of appropriate antimicrobials were identified as an important factor in hospital morbidity and mortality. These findings may have important implications for our current practice of empiric antibiotic treatment in HSCT patients.

Factors Associated With Clinical Deterioration Among Patients Hospitalized on the Wards at a Tertiary Cancer Hospital.

PURPOSE: Patients hospitalized outside the intensive care unit (ICU) frequently experience clinical deterioration. Little has been done to describe the landscape of clinical deterioration among inpatients with cancer. We aimed to describe the frequency of clinical deterioration among patients with cancer hospitalized on the wards at a major academic hospital and to identify independent risk factors for clinical deterioration among these patients. METHODS: This was a retrospective cohort study at a 1,300-bed urban academic hospital with a 138-bed inpatient cancer center. We included consecutive admissions to the oncology wards between January 1, 2014, and June 30, 2017. We defined clinical deterioration as the composite of ward death and transfer to the ICU. RESULTS: We evaluated 21,219 admissions from 9,058 patients. The composite outcome occurred during 1,945 admissions (9.2%): 1,365 (6.4%) had at least one ICU transfer, and 580 (2.7%) involved ward death. Logistic regression identified several independent risk factors for clinical deterioration, including the following: age (odds ratio [OR], 1.33 per decade; 95% CI, 1.07 to 1.67), male sex (OR, 1.15; 95% CI, 1.05 to 1.33), comorbidities, illness severity (OR, 1.11; 95% CI, 1.10 to 1.13), emergency admission (OR, 1.45; 95% CI, 1.26 to 1.67), hospitalization on particular wards (OR, 1.525; 95% CI, 1.326 to 1.67), bacteremia (OR, 1.24; 95% CI, 1.01 to 1.52), fungemia (OR, 3.76; 95% CI, 1.90 to 7.41), tumor lysis syndrome (OR, 3.01; 95% CI, 2.41 to 3.76), and receipt of antimicrobials (OR, 2.04; 95% CI, 1.72 to 2.42) and transfusions (OR, 1.65; 95% CI, 1.42 to 1.92). CONCLUSION: Clinical deterioration was common; it occurred in more than 9% of admissions. Factors independently associated with deterioration included comorbidities, admission source, infections, and blood product transfusion.