Acute respiratory distress syndrome readmissions: A nationwide cross-sectional analysis of epidemiology and costs of care.

BACKGROUND: Acute Respiratory Distress Syndrome affects approximately 10% of patients admitted to intensive care units internationally, with as many as 40%-52% of patients reporting re-hospitalization within one year. RESEARCH QUESTION/AIM: To describe the epidemiology of patients with acute respiratory distress syndrome who require 30-day readmission, and to describe associated costs. STUDY DESIGN AND METHODS: A cross-sectional analysis of the 2016 Healthcare Cost and Utilization Project's Nationwide Readmission Database, which is a population-based administrative database which includes discharge data from U.S. hospitals. Inclusion criteria: hospital discharge records for adults age > 17 years old, with a diagnosis of ARDS on index admission, with associated procedure codes for endotracheal intubation and/or invasive mechanical ventilation, who were discharged alive. Primary exposure is adult hospitalization for meeting criteria as described. The primary outcome measure is 30-day readmission rate, as well as patient characteristics and time distribution of readmissions. RESULTS: Nationally, 25,170 admissions meeting criteria were identified. Index admission mortality rate was 37.5% (95% confidence interval [CI], 36.2-38.8). 15,730 records of those surviving hospitalization had complete discharge information. 30-day readmission rate was 18.4%, with 14% of total readmissions occurring within 2 calendar days of discharge; these early readmissions had higher mortality risk (odds ratio 1.82, 95% CI 1.05-6.56) compared with readmission in subsequent days. For the closest all-cause readmission within 30 days, the mean cost was $26,971, with a total national cost of over $75.6 million. INTERPRETATION: Thirty-day readmission occurred in 18.4% of patients with acute respiratory distress syndrome in this sample, and early readmission is strongly associated with increased mortality compared to late readmission. Further research is needed to clarify whether the rehospitalizations or associated mortalities are preventable.

Improved outcomes over time for adult COVID-19 patients with acute respiratory distress syndrome or acute respiratory failure.

BACKGROUND: COVID-19's pulmonary manifestations are broad, ranging from pneumonia with no supplemental oxygen requirements to acute respiratory distress syndrome (ARDS) with acute respiratory failure (ARF). In response, new oxygenation strategies and therapeutics have been developed, but their large-scale effects on outcomes in severe COVID-19 patients remain unknown. Therefore, we aimed to examine the trends in mortality, mechanical ventilation, and cost over the first six months of the pandemic for adult COVID-19 patients in the US who developed ARDS or ARF. METHODS AND FINDINGS: The Vizient Clinical Data Base, a national database comprised of administrative, clinical, and financial data from academic medical centers, was queried for patients ≥ 18-years-old with COVID-19 and either ARDS or ARF admitted between 3/2020-8/2020. Demographics, mechanical ventilation, length of stay, total cost, mortality, and discharge status were collected. Mann-Kendall tests were used to assess for significant monotonic trends in total cost, mechanical ventilation, and mortality over time. Chi-square tests were used to compare mortality rates between March-May and June-August. 110,223 adult patients with COVID-19 ARDS or ARF were identified. Mean length of stay was 12.1±13.3 days and mean total cost was $35,991±32,496. Mechanical ventilation rates were 34.1% and in-hospital mortality was 22.5%. Mean cost trended downward over time (p = 0.02) from $55,275 (March) to $18,211 (August). Mechanical ventilation rates trended down (p<0.01) from 53.8% (March) to 20.3% (August). Overall mortality rates also decreased (p<0.01) from 28.4% (March) to 13.7% (August). Mortality rates in mechanically ventilated patients were similar over time (p = 0.45), but mortality in patients not requiring mechanical ventilation decreased from March-May compared to June-July (13.5% vs 4.6%, p<0.01). CONCLUSIONS: This study describes the outcomes of a large cohort with COVID-19 ARDS or ARF and the subsequent decrease in cost, mechanical ventilation, and mortality over the first 6 months of the pandemic in the US.

Equitably Allocating Resources during Crises: Racial Differences in Mortality Prediction Models.

Rationale: Crisis standards of care (CSCs) guide critical care resource allocation during crises. Most recommend ranking patients on the basis of their expected in-hospital mortality using the Sequential Organ Failure Assessment (SOFA) score, but it is unknown how SOFA or other acuity scores perform among patients of different races. Objectives: To test the prognostic accuracy of the SOFA score and version 2 of the Laboratory-based Acute Physiology Score (LAPS2) among Black and white patients. Methods: We included Black and white patients admitted for sepsis or acute respiratory failure at 27 hospitals. We calculated the discrimination and calibration for in-hospital mortality of SOFA, LAPS2, and modified versions of each, including categorical SOFA groups recommended in a popular CSC and a SOFA score without creatinine to reduce the influence of race. Measurements and Main Results: Of 113,158 patients, 27,644 (24.4%) identified as Black. The LAPS2 demonstrated higher discrimination (area under the receiver operating characteristic curve [AUC], 0.76; 95% confidence interval [CI], 0.76-0.77) than the SOFA score (AUC, 0.68; 95% CI, 0.68-0.69). The LAPS2 was also better calibrated than the SOFA score, but both underestimated in-hospital mortality for white patients and overestimated in-hospital mortality for Black patients. Thus, in a simulation using observed mortality, 81.6% of Black patients were included in lower-priority CSC categories, and 9.4% of all Black patients were erroneously excluded from receiving the highest prioritization. The SOFA score without creatinine reduced racial miscalibration. Conclusions: Using SOFA in CSCs may lead to racial disparities in resource allocation. More equitable mortality prediction scores are needed.

Prolonged Hospitalization Following Acute Respiratory Failure.

BACKGROUND: A better understanding of the clinical features associated with prolonged hospitalization in acute respiratory failure may allow for better-informed care planning. RESEARCH QUESTION: What are the incidence, mortality, cost, and clinical determinants of prolonged hospitalization among patients with acute respiratory failure (ARF)? STUDY DESIGN AND METHODS: Using the National Inpatient Sample data from 2004 to 2014, we identified adults 18 years and older with International Classification of Diseases, 9th edition (ICD-9) codes for ARF requiring mechanical ventilation for at least 2 days (ICD-9 518.81 or 518.82, 96.7 or 96.04, and 96.05). Outcomes studied included incidence, in-hospital mortality, cost of hospitalization, and associated patient-level and hospital-level characteristics. Trends were assessed by logistic regression, linear regression, and general linear modeling with Poisson distribution. RESULTS: Of the 5,539,567 patients with ARF, 77,665 (1.4%) had a prolonged length of stay (pLOS), defined as ≥ 60 days. Among those with pLOS, 52,776 (68%) survived to discharge. Over the study period, the incidence of pLOS decreased by 48%, in-patient mortality decreased by 18%, per-patient cost of care rose, but the percentage of the total cost of ARF care consumed by patients with pLOS did not significantly decrease (P = .06). Prolonged LOS was more likely to occur in urban teaching hospitals (OR, 6.8; 95% CI, 4.6-10.2; P < .001), hospitals located in the northeastern United States (OR, 3.6; 95% CI, 3.0-4.3; P < .001), and among patients with Medicaid insurance coverage (OR, 2.1; 95% CI, 1.9-2.4; P < .001). INTERPRETATION: From 2004 to 2014, incidence and mortality decreased among patients with ARF and pLOS, and although per-patient costs rose, the percentage of total cost of care remained stable. There is substantial variation in length of stay for patients with ARF by US region, hospital teaching status, and patient insurance coverage.

Financial Toxicity After Acute Respiratory Distress Syndrome: A National Qualitative Cohort Study.

OBJECTIVES: The financial burdens and subsequent related distress of medical care, referred to as financial toxicity, may limit access to beneficial treatments. However, financial toxicity after acute care is less described-and may be an important but underexplored mechanism preventing full recovery after critical illnesses such as acute respiratory distress syndrome. We sought to identify the mechanisms by which financial toxicity manifested in patients with acute respiratory distress syndrome, protective factors against such toxicity, and the consequences of financial toxicity to survivors' lives following acute respiratory distress syndrome. DESIGN: We conducted semistructured interviews following patients' hospitalization and during recovery as an ancillary study to a multicenter randomized clinical trial in acute respiratory distress syndrome. Patients were 9-16 months post randomization at the time of interview. SETTING AND PARTICIPANTS: The Reevaluation Of Systemic Early Neuromuscular Blockade trial examined the use of early neuromuscular blockade in mechanically ventilated patients with moderate/severe acute respiratory distress syndrome. We recruited consecutive surviving patients who were English speaking, consented to follow-up, and were randomized between December 11, 2017, and May 4, 2018 (n = 79) from 29 U.S. sites. MEASUREMENTS AND MAIN RESULTS: We asked about patients' perceptions of financial burden(s) that they associated with their acute respiratory distress syndrome hospitalization. Forty-six of 79 eligible acute respiratory distress syndrome survivors (58%) participated (from 22 sites); their median age was 56 (interquartile range 47-62). Thirty-one of 46 reported at least one acute respiratory distress syndrome-related financial impact. Financial toxicity manifested via medical bills, changes in insurance coverage, and loss of employment income. Respondents reported not working prior to acute respiratory distress syndrome, using Medicaid or Medicare, or, conversely, generous work benefits as factors which may have limited financial burdens. Patients reported multiple consequences of acute respiratory distress syndrome-related financial toxicity, including harms to their mental and physical health, increased reliance on others, and specific material hardships. CONCLUSIONS: Financial toxicity related to critical illness is common and may limit patients' emotional, physical, and social recovery after acute respiratory distress syndrome hospitalization for at least a year.

Association of Economic Status and Mortality in Patients with Acute Respiratory Distress Syndrome.

The high cost of treatment for acute respiratory distress syndrome (ARDS) is a concern for healthcare systems, while the impact of patients' socio-economic status on the risk of ARDS-associated mortality remains controversial. This study investigated associations between patients' income at the time of ARDS diagnosis and ARDS-specific mortality rate after treatment initiation. Data from records provided by the National Health Insurance Service of South Korea were used. Adult patients admitted for ARDS treatment from 2013 to 2017 were included in the study. Patients' income in the year of diagnosis was evaluated. A total of 14,600 ARDS cases were included in the analysis. The 30-day and 1-year mortality rates were 48.6% and 70.3%, respectively. In multivariable Cox regression model, we compared income quartiles, showing that compared to income strata Q1, the Q2 (P = 0.719), Q3 (P = 0.946), and Q4 (P = 0.542) groups of income level did not affect the risk of 30-day mortality, respectively. Additionally, compared to income strata Q1, the Q2 (P = 0.762), Q3 (P = 0.420), and Q4 (P = 0.189) strata did not affect the risk of 1-year mortality. Patient income at the time of ARDS diagnosis did not affect the risk of 30-day or 1-year mortality in the present study based on South Korea's health insurance data.

Effect of comorbidities on direct cost among type 2 diabetes mellitus (T2DM) patients in tertiary care government hospital in Uttarakhand, India: A primary data analysis of out of pocket expenditure.

BACKGROUND AND AIMS: The objective of present study was to estimate and compare the direct cost between diabetics and age and gender matched non-diabetics. It also aimed to estimate and compare the effect of various comorbidities on direct cost between cases and controls, while simultaneously trying to determine the predictors of direct cost among T2DM patients. METHODS: A hospital-based pair matched case-control study was conducted in a tertiary care hospital in Garhwal division of Uttarakhand, India to accomplish the objectives of study. Regression analysis was applied to determine the predictors of direct cost among diabetics. RESULTS: Mean annual direct cost among diabetics was estimated to be US$ 104.6 (Indian Rupees (INR) 7338.9)) in comparison to US$ 27.8 (INR 1905.8) among non-diabetics. The total cost among cases was significantly higher than controls, if they had comorbidities from CVS, nervous, ophthalmic, respiratory and musculoskeletal system. Gender, education, duration of diabetes and number of comorbidities were significant predictors in estimating the direct cost among cases. For each one-year increase in duration of diabetes, direct cost increased by 13.1 unit. CONCLUSIONS: The study provides us conclusive evidence of significantly higher expenditure among diabetics in comparison to non-diabetics. An effect on direct cost among diabetics was observed with types and increasing number of comorbidities.

Mortality and costs following extracorporeal membrane oxygenation in critically ill adults: a population-based cohort study.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in critically ill patients. Little is known about population-level short- and long-term outcomes following ECMO, including healthcare use and health system cost across a wide range of sectors. METHODS: Population-based cohort study in Ontario, Canada (October 1, 2009-March 31, 2017) of adult patients (≥ 18 years) receiving ECMO for cardiorespiratory support. We captured outcomes through linkage to health administrative databases. Primary outcome was mortality during hospitalization, as well as at 7 days, 30 days, 1 year, 2 years, and 5 years following ECMO initiation. We analyzed health system costs (in Canadian dollars) in the 1 year following the date of the index admission. RESULTS: A total of 692 patients were included. Mean (standard deviation [SD]) age was 51.3 (16.0) years. Median (interquartile range [IQR]) time to ECMO initiation from date of admission was 2 (0-9) days. In-hospital mortality was 40.0%. Mortality at 1 year, 2 years, and 5 years was 45.1%, 49.0%, and 57.4%, respectively. Among survivors, 78.4% were discharged home, while 21.2% were discharged to continuing care. Median (IQR) total costs in the 1 year following admission among all patients were Canadian $130,157 (Canadian $58,645-Canadian $240,763), of which Canadian $91,192 (Canadian $38,507-Canadian $184,728) were attributed to inpatient care. CONCLUSIONS: Hospital mortality among critically ill adults receiving ECMO for advanced cardiopulmonary support is relatively high, but does not markedly increase in the years following discharge. Survivors are more likely to be discharged home than to continuing care. Median costs are high, but largely reflect inpatient hospital costs, and not costs incurred following discharge.

Use and costs of inhaled nitric oxide and inhaled epoprostenol in adult critically ill patients: A quality improvement project.

PURPOSE: Inhaled epoprostenol and inhaled nitric oxide are pulmonary vasodilators commonly used in the management of acute respiratory distress syndrome and right ventricular failure; however, they have vastly different cost profiles. The purpose of the project was to transition from nitric oxide to epoprostenol as the inhaled pulmonary vasodilator (IPV) of choice in adult critically ill patients and evaluate the effect of the transition on associated usage and costs. METHODS: A single-center, prospective, before and after quality improvement project including adult patients receiving inhaled nitric oxide, inhaled epoprostenol, or both was conducted in 7 adult intensive care units, operating rooms, and postanesthesia care units of a tertiary care academic medical center. The total number of patients, hours of therapy, and costs for each agent were compared between stages of protocol implementation and annually. RESULTS: Seven hundred twenty-nine patients received inhaled nitric oxide, inhaled epoprostenol, or both during the study period. The monthly inhaled nitric oxide use in number of patients, hours, and cost decreased during all stages of the project (p < 0.01). The monthly inhaled epoprostenol use in number of patients, hours, and cost increased during all stages (p < 0.01). Overall, total IPV use increased during the study. However, despite this increase in usage, there was a 47% reduction in total IPV cost. CONCLUSION: Implementation of a staged protocol to introduce and expand inhaled epoprostenol use in adult critically ill patients resulted in decreased use and cost of inhaled nitric oxide. The total cost of all IPV was decreased by 47% despite increased IPV use.

Acute Respiratory Distress Syndrome: Cost (Early and Long-Term).

Costs of care in the intensive care unit are a frequent area of concern in our current health care system. Utilization of critical care services in the United States, particularly near the end of life, has been steadily increasing and will continue to do so. Acute respiratory distress syndrome (ARDS) is a common and important complication of critical illness. Patients with ARDS frequently experience prolonged hospitalizations and consume significant health care resources. Many patients are discharged with functional limitations and require significant postdischarge services. These patients have a high susceptibility to new complications which require significant additional health care resources. There is a slowly growing literature on the cost-effectiveness of the treatment of ARDS; despite its high costs, treatment remains a cost-effective intervention by most societal standards. However, when ARDS leads to prolonged mechanical ventilation, treatment may become less cost-effective. In addition, the provision of extracorporeal life support adds another layer of complexity to these cases. Small reductions in intensive care unit length of stay may benefit patients, but they do not lead to significant reductions in overall hospital costs. Early discharge to postacute care facilities can reduce hospital costs but is unlikely to significantly decrease costs for an entire episode of illness. Improved effectiveness of communication between clinicians and patients or their surrogates could help avoid costly interventions with poor expected outcomes. However, the most significant cost-saving interventions are early recognition and treatment of conditions to potentially prevent the development of this serious complication.

The Cost-Effectiveness of Interventions to Increase Utilization of Prone Positioning for Severe Acute Respiratory Distress Syndrome.

OBJECTIVES: Despite strong evidence supporting proning in acute respiratory distress syndrome, few eligible patients receive it. This study determines the cost-effectiveness of interventions to increase utilization of proning for severe acute respiratory distress syndrome. DESIGN: We created decision trees to model severe acute respiratory distress syndrome from ICU admission through death (societal perspective) and hospital discharge (hospital perspective). We assumed patients received low tidal volume ventilation. We used short-term outcome estimates from the PROSEVA trial and longitudinal cost and benefit data from cohort studies. In probabilistic sensitivity analyses, we used distributions for each input that included the fifth to 95th percentile of its CI. SETTING: ICUs that care for patients with acute respiratory distress syndrome. SUBJECTS: Patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: The implementation of a hypothetical intervention to increase the appropriate utilization of prone positioning. MEASUREMENTS AND MAIN RESULTS: In the societal perspective model, an intervention that increased proning utilization from 16% to 65% yielded an additional 0.779 (95% CI, 0.088-1.714) quality-adjusted life years at an additional long-term cost of $31,156 (95% CI, -$158 to $92,179) (incremental cost-effectiveness ratio = $38,648 per quality-adjusted life year [95% CI, $1,695-$98,522]). If society was willing to pay $100,000 per quality-adjusted life year, any intervention costing less than $51,328 per patient with moderate to severe acute respiratory distress syndrome would represent good value. From a hospital perspective, the intervention yielded 0.072 (95% CI, 0.008-0.147) more survivals-to-discharge at a cost of $5,242 (95% CI, -$19,035 to $41,019) (incremental cost-effectiveness ratio = $44,615 per extra survival [95% CI, -$250,912 to $558,222]). If hospitals were willing to pay $100,000 per survival-to-discharge, any intervention costing less than $5,140 per patient would represent good value. CONCLUSIONS: Interventions that increase utilization of proning would be cost-effective from both societal and hospital perspectives under many plausible cost and benefit assumptions.

Economic Evaluation of Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation is increasingly being used to support patients with severe acute respiratory distress syndrome, but its cost-effectiveness is unknown. We assessed the cost-utility of venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults compared with standard lung protective ventilation from the perspective of the healthcare system. DESIGN: We conducted a cost-utility analysis with a cohort state transition decision model using a lifetime time horizon, 1.5% discount rate, and outcomes reported as cost per quality-adjusted life year. Literature reviews were conducted to inform the model variables. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in the model. SETTING: Canadian publicly funded healthcare system. PATIENTS: Hypothetical cohort of adults with severe acute respiratory distress syndrome. INTERVENTIONS: Venovenous extracorporeal membrane oxygenation or standard lung protective ventilation. MEASUREMENTS AND MAIN RESULTS: In our model, the use of venovenous extracorporeal membrane oxygenation compared with lung protective ventilation resulted in a gain of 5.2 life years and 4.05 quality-adjusted life years, at an additional lifetime cost of $145,697 Canadian dollars. The incremental cost-effectiveness ratio was $36,001/quality-adjusted life year. Sensitivity analyses show that the incremental cost-effectiveness ratio is sensitive to the efficacy of extracorporeal membrane oxygenation therapy and costs. CONCLUSIONS: Based on current data, venovenous extracorporeal membrane oxygenation is cost-effective for patients with severe acute respiratory distress syndrome. Additional evidence on the efficacy of venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome and in different subgroups of patients will allow for greater certainty in its cost-effectiveness.

Health care utilization and the cost of posttraumatic acute respiratory distress syndrome care.

BACKGROUND: Posttraumatic acute respiratory distress syndrome (ARDS) is associated with prolonged mechanical ventilation and longer hospitalizations. The relationship between posttraumatic ARDS severity and financial burden has not been previously studied. We hypothesized that increasing ARDS severity is associated with incrementally higher health care costs. METHODS: Adults arriving as the highest level of trauma activation were enrolled in an ongoing prospective cohort study. Patients who survived 6 hours or longer are included in the analysis. Blinded review of chest radiographs was performed by two independent physicians for any intubated patient with PaO2:FIO2 ratio of 300 mmHg or lower during the first 8 days of admission. The severity of ARDS was classified by the Berlin criteria. Hospital charge data were used to perform standard costing analysis. RESULTS: Acute respiratory distress syndrome occurred in 13% (203 of 1,586). The distribution of disease severity was 33% mild, 42% moderate, and 25% severe. Patients with ARDS were older (41 years vs. 35 years, p < 0.01), had higher median Injury Severity Score (30 vs. 10, p < 0.01), more chest injury (Abbreviated Injury Scale score, ≥ 3: 51% vs. 21%, p < 0.01), and blunt mechanisms (85% vs. 53%, p < 0.01). By ARDS severity, there was no significant difference in age, mechanism, or rate of traumatic brain injury. Increasing ARDS severity was associated with higher Injury Severity Score and higher mortality rates. Standardized total hospital charges were fourfold higher for patients who developed ARDS compared with those who did not develop ARDS (US $434,000 vs. US $96,000; p < 0.01). Furthermore, the daily hospital charges significantly increased across categories of worsening ARDS severity (mild, US $20,451; moderate, US $23,994; severe, US $33,316; p < 0.01). CONCLUSION: The development of posttraumatic ARDS is associated with higher health care costs. Among trauma patients who develop ARDS, total hospital charges per day increase with worsening severity of disease. Prevention, early recognition, and treatment of ARDS after trauma are potentially important objectives for efforts to control health care costs in this population. LEVEL OF EVIDENCE: Economic and value-based evaluations, level IV.

Comparison of incidence and cost of influenza between healthy and high-risk children <60 months old in Thailand, 2011-2015.

INTRODUCTION: Thailand recommends influenza vaccination for children aged 6 months to <36 months, but investment in vaccine purchase is limited. To inform policy decision with respect to influenza disease burden and associated cost in young children and to support the continued inclusion of children as the recommended group for influenza vaccination, we conducted a prospective cohort study of children in Bangkok hospital to estimate and compare influenza incidence and cost between healthy and high-risk children. METHODS: Caregivers of healthy children and children with medical conditions ('high-risk') aged <36 months were called weekly for two years to identify acute respiratory illness (ARI) episodes and collect illness-associated costs. Children with ARI were tested for influenza viruses by polymerase chain reaction. Illnesses were categorized as mild or severe depending on whether children were hospitalized. Population-averaged Poisson models were used to compare influenza incidence by risk group. Quantile regression was used to examine differences in the median illness expenses. RESULTS: During August 2011-September 2015, 659 healthy and 490 high-risk children were enrolled; median age was 10 months. Incidence of mild influenza-associated ARI was higher among healthy than high-risk children (incidence rate ratio [IRR]: 1.67; 95% confidence interval [CI]: 1.13-2.48). Incidence of severe influenza-associated ARI did not differ (IRR: 0.40; 95% CI: 0.11-1.38). The median cost per mild influenza-associated ARI episode was $22 among healthy and $25 among high-risk children (3-4% of monthly household income; difference in medians: -$1; 95% CI for difference in medians: -$9 to $6). The median cost per severe influenza-associated ARI episode was $232 among healthy and $318 among high-risk children (26-40% and 36-54% of monthly household income, respectively; difference in medians: 110; 95% CI for difference in medians: -$352 to $571). CONCLUSIONS: Compared to high-risk children, healthy children had higher incidence of mild influenza-associated ARI but not severe influenza-associated ARI. Costs of severe influenza-associated ARI were substantial. These findings support the benefit of annual influenza vaccination in reducing the burden of influenza and associated cost in young children.

Cost Analysis of Noninvasive Helmet Ventilation Compared with Use of Noninvasive Face Mask in ARDS.

Intensive care unit (ICU) costs have doubled since 2000, totalling 108 billion dollars per year. Acute respiratory distress syndrome (ARDS) has a prevalence of 10.4% and a 28-day mortality of 34.8%. Noninvasive ventilation (NIV) is used in up to 30% of cases. A recent randomized controlled trial by Patel et al. (2016) showed lower intubation rates and 90-day mortality when comparing helmet to face mask NIV in ARDS. The population in the Patel et al. trial was used for cost analysis in this study. Projections of cost savings showed a decrease in ICU costs by $2527 and hospital costs by $3103 per patient, along with a 43.3% absolute reduction in intubation rates. Sensitivity analysis showed consistent cost reductions. Projected annual cost savings, assuming the current prevalence of ARDS, were $237538 in ICU costs and $291682 in hospital costs. At a national level, using yearly incidence of ARDS cases in American ICUs, this represents $449 million in savings. Helmet NIV, compared to face mask NIV, in nonintubated patients with ARDS, reduces ICU and hospital direct-variable costs along with intubation rates, LOS, and mortality. A large-scale cost-effectiveness analysis is needed to validate the findings.

Lessons to learn from epidemiologic studies in ARDS.

PURPOSE OF REVIEW: Recent advances in our understanding of the epidemiology of ARDS has generated key insights into the incidence, risk factors, demographics, management and outcomes from this devastating clinical syndrome. RECENT FINDINGS: ARDS occurs in 10% of all ICU patients, in 23% of all mechanically ventilated patients, with 5.5 cases per ICU bed each year. Although some regional variation exists regarding ARDS incidence, this may be less than previously thought. Subphenotypes are increasingly identified within the ARDS cohort, with studies identifying a 'hyperinflammatory' or 'reactive' subgroup that has a higher mortality, and may respond differently to therapeutic interventions. Demographic factors, such as race, may also affect the therapeutic response. Although mortality in ARDS is decreasing in clinical trials, it remains unchanged at approximately 40% in major observational studies. Modifiable ventilatory management factors, including PEEP, airway pressures, and respiratory rate are associated with mortality in ARDS. Hospital and ICU organizational factors play a role in outcome, whereas socioeconomic status is independently associated with survival in patients with ARDS. The Kigali adaptation of the Berlin ARDS definition may provide useful insights into the burden of ARDS in the developing world. SUMMARY: ARDS exerts a substantial disease burden, with 40% of patients dying in hospital. Diverse factors, including patient-related factors such as age and illness severity, country level socioeconomic status, and ventilator management and ICU organizational factors each contribute to outcome from ARDS. Addressing these issues provides opportunities to improve outcome in patients with ARDS.

Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study.

BACKGROUND: Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). METHODS: LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensive-care units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. FINDINGS: Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO2) to the fractional concentration of oxygen in inspired air (FiO2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. INTERPRETATION: Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated. FUNDING: European Society of Intensive Care Medicine, St Michael's Hospital, University of Milan-Bicocca.

Simvastatin for patients with acute respiratory distress syndrome: long-term outcomes and cost-effectiveness from a randomised controlled trial.

BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.

Healthcare utilization and costs in ARDS survivors: a 1-year longitudinal national US multicenter study.

PURPOSE: To evaluate (1) post-discharge healthcare utilization and estimated costs in ARDS survivors, and (2) the association between patient and intensive care-related variables, and 6-month patient status, with subsequent hospitalization and costs. METHODS: Longitudinal cohort study enrolling from four ARDSNet trials in 44 US hospitals. Healthcare utilization was collected via structured interviews at 6 and 12 months post-ARDS, and hospital costs estimated via the Medical Expenditure Panel Survey. Adjusted odds ratios for hospitalization and adjusted relative medians for hospital costs were calculated using marginal two-part regression models. RESULTS: Of 859 consenting survivors, 839 (98%) reported healthcare utilization, with 52% female and a mean age of 49 years old. Over 12 months, 339 (40%) patients reported at least one post-discharge hospitalization, with median estimated hospital costs of US$18,756 (interquartile range $7852-46,174; 90th percentile $101,500). Of 16 patient baseline and ICU variables evaluated, only cardiovascular comorbidity and length of stay were associated with hospitalization, and sepsis was associated with hospital costs. At 6-month assessment, better patient-reported physical activity and quality of life status were associated with fewer hospitalizations and lower hospital costs during subsequent follow-up, and worse psychiatric symptoms were associated with increased hospitalizations. CONCLUSIONS: This multicenter longitudinal study found that 40% of ARDS survivors reported at least one post-discharge hospitalization during 12-month follow-up. Few patient- or ICU-related variables were associated with hospitalization; however, physical, psychiatric, and quality of life measures at 6-month follow-up were associated with subsequent hospitalization. Interventions to reduce post-ARDS morbidity may be important to improve patient outcomes and reduce healthcare utilization.

Joblessness and Lost Earnings after Acute Respiratory Distress Syndrome in a 1-Year National Multicenter Study.

RATIONALE: Following acute respiratory distress syndrome (ARDS), joblessness is common but poorly understood. OBJECTIVES: To evaluate the timing of return to work after ARDS, and associated risk factors, lost earnings, and changes in healthcare coverage Methods: Over 12-month longitudinal follow-up, ARDS survivors from 43 U.S. ARDSNet hospitals provided employment and healthcare coverage data via structured telephone interviews. Factors associated with the timing of return to work were assessed using Fine and Gray regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. MEASUREMENTS AND MAIN RESULTS: Of 922 consenting survivors, 386 (42%) were employed before ARDS (56% male; mean ± SD age, 45 ± 13 yr), with seven dying by 12-month follow-up. Of 379 previously employed 12-month survivors, 166 (44%) were jobless at 12-month follow-up. Accounting for competing risks of death and retirement, half of enrolled and previously employed survivors returned to work by 13 weeks after hospital discharge, with 68% ever returning by 12 months. Delays in return to work were associated with longer hospitalization and older age among nonwhite survivors. Over 12-month follow-up, 274 (71%) survivors accrued lost earnings, averaging $26,949 ± $22,447 (60% of pre-ARDS annual earnings). Jobless survivors experienced a 14% (95% confidence interval, 5-22%; P = 0.002) absolute decrease in private health insurance (from 44% pre-ARDS) and a 16% (95% confidence interval, 7-24%; P < 0.001) absolute increase in Medicare and Medicaid (from 33%). CONCLUSIONS: At 12 months after ARDS, nearly one-half of previously employed survivors were jobless. Post-ARDS joblessness is associated with readily identifiable patient and hospital variables and accompanied by substantial lost earnings and a shift toward government-funded healthcare coverage.