Tereza Martinu

One-Year Trajectories of Care and Resource Utilization for Recipients of Prolonged Mechanical Ventilation: A Cohort Study

BACKGROUND Growing numbers of critically ill patients receive prolonged mechanical ventilation. Little is known about the patterns of care as patients transition from acute care hospitals to postacute care facilities or about the associated resource utilization. OBJECTIVE To describe 1-year trajectories of care and resource utilization for patients receiving prolonged mechanical ventilation. DESIGN 1-year prospective cohort study. SETTING 5 intensive care units at Duke University Medical Center, Durham, North Carolina. PARTICIPANTS 126 patients receiving prolonged mechanical ventilation (defined as ventilation for >or=4 days with tracheostomy placement or ventilation for >or=21 days without tracheostomy), as well as their 126 surrogates and 54 intensive care unit physicians, enrolled consecutively over 1 year. MEASUREMENTS Patients and surrogates were interviewed in the hospital, as well as 3 and 12 months after discharge, to determine patient survival, functional status, and facility type and duration of postdischarge care. Physicians were interviewed in the hospital to elicit prognoses. Institutional billing records were used to assign costs for acute care, outpatient care, and interfacility transportation. Medicare claims data were used to assign costs for postacute care. RESULTS 103 (82%) hospital survivors had 457 separate transitions in postdischarge care location (median, 4 transitions [interquartile range, 3 to 5 transitions]), including 68 patients (67%) who were readmitted at least once. Patients spent an average of 74% (95% CI, 68% to 80%) of all days alive in a hospital or postacute care facility or receiving home health care. At 1 year, 11 patients (9%) had a good outcome (alive with no functional dependency), 33 (26%) had a fair outcome (alive with moderate dependency), and 82 (65%) had a poor outcome (either alive with complete functional dependency [4 patients; 21%] or dead [56 patients; 44%]). Patients with poor outcomes were older, had more comorbid conditions, and were more frequently discharged to a postacute care facility than patients with either fair or good outcomes (P < 0.05 for all). The mean cost per patient was

Expectations and Outcomes of Prolonged Mechanical Ventilation

306,135 (SD,

Acute Rejection and Humoral Sensitization in Lung Transplant Recipients

285,467), and total cohort cost was

Baseline 6-Min Walk Distance Predicts Survival in Lung Transplant Candidates

38.1 million, for an estimated

Progressive multifocal leukoencephalopathy following heightened immunosuppression after lung transplant.

3.5 million per independently functioning survivor at 1 year. LIMITATION The results of this single-center study may not be applicable to other centers. CONCLUSION Patients receiving prolonged mechanical ventilation have multiple transitions of care, resulting in substantial health care costs and persistent, profound disability. The optimism of surrogate decision makers should be balanced by discussions of these outcomes when considering a course of prolonged life support. PRIMARY FUNDING SOURCE None.

Acute cellular rejection and humoral sensitization in lung transplant recipients.

Objective:To compare prolonged mechanical ventilation decision-makers’ expectations for long-term patient outcomes with prospectively observed outcomes and to characterize important elements of the surrogate-physician interaction surrounding prolonged mechanical ventilation provision. Prolonged mechanical ventilation provision is increasing markedly despite poor patient outcomes. Misunderstanding prognosis in the prolonged mechanical ventilation decision-making process could provide an explanation for this phenomenon. Design:Prospective observational cohort study. Setting:Academic medical center. Patients:A total of 126 patients receiving prolonged mechanical ventilation. Interventions:None. Measurements and Main Results:Participants were interviewed at the time of tracheostomy placement about their expectations for 1-yr patient survival, functional status, and quality of life. These expectations were then compared with observed 1-yr outcomes measured with validated questionnaires. The 1-yr follow-up was 100%, with the exception of patient death or cognitive inability to complete interviews. At 1 yr, only 11 patients (9%) were alive and independent of major functional status limitations. Most surrogates reported high baseline expectations for 1-yr patient survival (n = 117, 93%), functional status (n = 90, 71%), and quality of life (n = 105, 83%). In contrast, fewer physicians described high expectations for survival (n = 54, 43%), functional status (n = 7, 6%), and quality of life (n = 5, 4%). Surrogate-physician pair concordance in expectations was poor (all &kgr; = <0.08), as was their accuracy in outcome prediction (range = 23%–44%). Just 33 surrogates (26%) reported that physicians discussed what to expect for patients’ likely future survival, general health, and caregiving needs. Conclusions:One-year patient outcomes for prolonged mechanical ventilation patients were significantly worse than expected by patients’ surrogates and physicians. Lack of prognostication about outcomes, discordance between surrogates and physicians about potential outcomes, and surrogates’ unreasonably optimistic expectations seem to be potentially modifiable deficiencies in surrogate-physician interactions.

Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter Study

Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation

In a large, prospectively followed, two‐center cohort of patients listed for lung transplantation (n = 376), we used Cox proportional hazards models to determine the importance of baseline 6‐min walk distance (6MWD) in predicting patient survival. 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time‐varying covariate (HR for each 500 ft increase in 6MWD = 0.57, 95% CI: 0.43–0.77, p = 0.0002). 6MWD remained an important predictor of survival in models that considered only survival to transplant (HR for each 500 ft increase in 6MWD = 0.41, 95% CI: 0.27–0.62, p < 0.0001) or survival only after transplant (HR for each 500 ft increase in 6MWD = 0.40, 95% CI: 0.22–0.72, p = 0.002). Unadjusted Kaplan‐Meier analysis demonstrates significantly different survival by 6MWD tertiles (<900, 900–1200, or >1200 ft, p‐value = 0.0001). In the overall model, 6MWD prediction of survival was relatively homogeneous across disease category (6MWD by disease interaction term, p‐value = 0.63). Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation. The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation.

Neurobehavioral Functioning and Survival Following Lung Transplantation

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the JC virus that occurs in the setting of immunosuppression. A 38-year-old female lung transplant recipient at our institution received treatment for episodes of acute rejection with steroids, anti-thymocyte globulin and alemtuzumab, in addition to maintenance immunosuppression. She was diagnosed with PML 13 months after the last episode of rejection, for which she had received alemtuzumab. Despite attempted treatment with cidofovir followed by mirtazapine, PML progressed, and she ultimately died of an acute pulmonary infection and respiratory failure. We provide a detailed clinical and radiographic description of PML in a lung transplant patient and highlight its potential relationship to intensive immunosuppression, as the disease developed in the setting of markedly reduced CD4 counts.

Acute allograft rejection: cellular and humoral processes.

Despite the recent development of many new immunosuppressive agents for use in transplantation, acute cellular and humoral rejection represent extremely prevalent and serious complications after lung transplantation. Acute cellular rejection, defined as perivascular or bronchiolar mononuclear inflammation, affects over 50% of lung transplant recipients within the first year. Furthermore, the frequency and severity of acute rejections are the most important risk factors for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that severely limits survival after lung transplantation. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Emerging evidence also suggests that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens and is associated with an increased risk for BOS. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. Herein, we review the clinical presentation, diagnosis, mechanisms, and treatment of cellular and humoral rejection after lung transplantation.