The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.

Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.

Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism.

UNLABELLED: ESSENTIALS: When high probability of pulmonary embolism (PE), sensitivity of computed tomography (CT) is unclear. We investigated the sensitivity of multidetector CT among 134 patients with a high probability of PE. A normal CT alone may not safely exclude PE in patients with a high clinical pretest probability. In patients with no clear alternative diagnosis after CTPA, further testing should be strongly considered. BACKGROUND: Whether patients with a negative multidetector computed tomographic pulmonary angiography (CTPA) result and a high clinical pretest probability of pulmonary embolism (PE) should be further investigated is controversial. METHODS: This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria. Among patients with a negative CTPA result, the diagnosis of PE required at least one of the following conditions: ventilation/perfusion lung scan showing a high probability of PE in a patient with no history of PE, abnormal findings on venous ultrasonography in a patient without previous deep vein thrombosis at that site, or the occurrence of venous thromboembolism (VTE) in a 3-month follow-up period after anticoagulation was withheld because of a negative multidetector CTPA result. RESULTS: We identified 498 patients with a priori clinical assessment of a high probability of PE and a completed CTPA study. CTPA excluded PE in 134 patients; in these patients, the pooled incidence of VTE was 5.2% (seven of 134 patients; 95% confidence interval [CI] 1.5-9.0). Five patients had VTEs that were confirmed by an additional imaging test despite a negative CTPA result (five of 48 patients; 10.4%; 95% CI 1.8-19.1), and two patients had objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months (two of 86 patients; 2.3%; 95% CI 0-5.5). None of the patients had a fatal PE during follow-up. CONCLUSIONS: A normal multidetector CTPA result alone may not safely exclude PE in patients with a high clinical pretest probability.

Emotional well-being of living kidney donors: findings from the RELIVE Study.

Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963-2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010-2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9>10) was similar to National Health and Nutrition Examination Survey participants (7%, p=0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p=0.05). Postdonation predictors of depressive symptoms included nonwhite race OR=2.00, p=0.020), younger age at donation (OR=1.33 per 10 years, p=0.002), longer recovery time from donation (OR=1.74, p=0.0009), greater financial burden (OR=1.32, p=0.013) and feeling morally obligated to donate (OR=1.23, p=0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention.

Morbidity and mortality of live lung donation: results from the RELIVE study.

The Renal and Lung Living Donors Evaluation Study assesses outcomes of live lung (lobectomy) donors. This is a retrospective cohort study at University of Southern California (USC) and Washington University (WASHU) Medical Centers (1993­2006), using medical records to assess morbidity and national databases to ascertain postdonation survival and lung transplantation. Serious complications were defined as those that required significant treatment, were potentially life-threatening or led to prolonged hospitalization. The 369 live lung donors (287 USC, 82 WASHU) were predominantly white, non-Hispanic and male; 72% had a biological relationship to the recipient, and 30% were recipient parents. Serious complications occurred in 18% of donors; 2.2% underwent reoperation and 6.5% had an early rehospitalization. The two centers had significantly different incidences of serious complications (p < 0.001). No deaths occurred and no donors underwent lung transplantation during 4000+ person-years of follow-up (death: minimum 4, maximum 17 years; transplant: minimum 5, maximum 19). Live lung donation remains a potential option for recipients when using deceased donor lungs lacks feasibility. However, the use of two live donors for each recipient and the risk of morbidity associated with live lung donation do not justify this approach when deceased lung donors remain available. Center effects and long-term live donor outcomes require further evaluation.

Prognostic significance of tricuspid annular displacement in normotensive patients with acute symptomatic pulmonary embolism.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is an emerging prognostic indicator in patients with acute symptomatic pulmonary embolism (PE). METHODS AND RESULTS: We prospectively examined 782 normotensive patients with PE who underwent echocardiography in a multicenter study. As compared with patients with a TAPSE of > 1.6 cm, those with a TAPSE of ≤ 1.6 cm had increased systolic pulmonary artery pressure (53.7 ± 16.7 mmHg vs. 40.0 ± 15.5 mmHg, P < 0.001), right ventricle (RV) end-diastolic diameter (3.5 ± 0.8 cm vs. 3.0 ± 0.6 cm, P < 0.001), and RV to left ventricle end-diastolic diameter ratio (1.0 ± 0.3 vs. 0.8 ± 0.2, P < 0.001), and a higher prevalence of RV free wall hypokinesis (68% vs. 11%, P < 0.001). Patients with a TAPSE of ≤ 1.6 cm at the time of PE diagnosis were significantly more likely to die from any cause (hazard ratio [HR] 2.3; 95% confidence interval [CI] 1.2-4.7; P = 0.02) and from PE (HR 4.4; 95% CI 1.3-15.3; P = 0.02) during follow-up. In an external validation cohort of 1326 patients with acute PE enrolled in the international multicenter Registro Informatizado de la Enfermedad TromboEmbólica, a TAPSE of ≤ 1.6 cm remained a significant predictor of all-cause mortality (HR 2.1; 95% CI 1.3-3.2; P = 0.001) and PE-specific mortality (HR 2.5; 95% CI 1.2-5.2; P = 0.01). CONCLUSIONS: In normotensive patients with PE, TAPSE reflects right ventricular function. For these patients, TAPSE is independently predictive of survival.

Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis.

BACKGROUND: The ability of computed tomography (CT)-assessed right ventricular dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism (PE) at high risk of mortality or adverse outcome lacks clarity. METHODS AND RESULTS: We performed a systematic review and a meta-analysis of studies in normotensive patients with acute PE to assess the prognostic value of CT-assessed RVD for death and a predefined composite outcome of PE-related complications. We conducted unrestricted searches of MEDLINE and EMBASE from 1980 to March 2013, and used the terms 'computed tomography', 'pulmonary embolism', and 'prognos*'. We used a random-effects model to pool study results, funnel-plot inspection to evaluate for publication bias, and I(2) testing to assess for heterogeneity. The analysis included data from 10 studies (2288 patients). Overall, 99 of 1268 patients with RVD assessed by CT died (7.8%; 95% confidence interval [CI] 6.3-9.3) as compared with 52 of 1020 without RVD (5.1%; 95% CI 3.7-6.4). CT-assessed RVD had significant associations with mortality (odds ratio [OR] 1.8; 95% CI 1.3-2.6), with death resulting from PE (OR 7.4; 95% CI 1.4-39.5), and with PE-related complications (OR 2.4; 95% CI 1.2-4.7). Pooled likelihood ratios (LRs) were not extreme (negative LR 0.71; 95% CI 0.57-0.89; and positive LR 1.27; 95% CI 1.12-1.43). CONCLUSIONS: Although RVD assessed by CT showed an association with an increased risk of mortality in patients with hemodynamically stable PE, it resulted in only small increases in the ability to classify risk.

Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary embolism.

BACKGROUND: While the primary therapy for most patients with a pulmonary embolism (PE) consists of anticoagulation, the efficacy of thrombolysis relative to standard therapy remains unclear. METHODS: In this retrospective cohort study of 15,944 patients with an objectively confirmed symptomatic acute PE, identified from the multicenter, international, prospective, Registro Informatizado de la Enfermedad TromboEmbólica (RIETE registry), we aimed to assess the association between thrombolytic therapy and all-cause mortality during the first 3 months after the diagnosis of a PE. After creating two subgroups, stratified by systolic blood pressure (SBP) (< 100 mm Hg vs. other), we used propensity score-matching for a comparison of patients who received thrombolysis to those who did not in each subgroup. RESULTS: Patients who received thrombolysis were younger, had fewer comorbid diseases and more signs of clinical severity compared with those who did not receive it. In the subgroup with systolic hypotension, analysis of propensity score-matched pairs (n = 94 pairs) showed a non-statistically significant but clinically relevant lower risk of death for thrombolysis compared with no thrombolysis (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.36-1.46; P = 0.37). In the normotensive subgroup, analysis of propensity score-matched pairs (n = 217 pairs) showed a statistically significant and clinically meaningful increased risk of death for thrombolysis compared with no thrombolysis (OR 2.32; 95% CI, 1.15-4.68; P = 0.018). When we imputed data for missing values for echocardiography and troponin tests in the group of normotensive patients, we no longer detected the increased risk of death associated with thrombolytic therapy. CONCLUSIONS: In normotensive patients with acute symptomatic PE, thrombolytic therapy is associated with a higher risk of death than no thrombolytic therapy. In hemodynamically unstable patients, thrombolytic therapy is possibly associated with a lower risk of death than no thrombolytic therapy. However, study design limitations do not imply a causal relationship between thrombolytics and outcome.

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism.

BACKGROUND: Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise. METHODS: We assessed the cause of death during the first 30 days after the diagnosis of acute symptomatic PE in a consecutive series of patients. We also assessed the prognostic characteristics of the simplified Pulmonary Embolism Severity Index (sPESI) and cardiac troponin I (cTnI) obtained at the time of PE diagnosis. RESULTS: During the first 30 days after diagnosis, 127 of the 1291 patients died (9.8%; 95% confidence interval [CI], 8.2-11.5). Sixty patients (4.6%; 95% CI, 3.5-5.8) died from definite or possible PE, and 67 (5.2%; 95% CI, 4.0-6.4) died from other causes (cancer 25, infection 18, hemorrhage 7, heart failure 7, chronic obstructive pulmonary disease 5, renal failure 1, seizures 1, unknown 3). The sPESI predicted all-cause (odds ratio [OR], 5.97; 95% CI, 1.74-20.54; P < 0.01) and PE-associated mortality (OR, 8.79; 95% CI, 1.12-68.79; P = 0.04). cTnI only predicted PE-associated mortality (adjusted OR, 2.39; 95% CI, 1.25-4.57; P < 0.01). For all-cause mortality, the sPESI low-risk strata had a negative predictive value of 98.8% (95% CI, 97.4-100) in comparison with 91.3% (95% CI, 88.9-93.6) for the cTnI. CONCLUSIONS: Within the first 30 days after the diagnosis of acute symptomatic PE, death due to PE and death due to other causes occur in a similar proportion of patients. As cTnI only predicted PE-associated mortality, low-risk sPESI had a higher negative predictive value for all-cause mortality compared with cTnI.

Lung transplantation in the United States, 1999-2008.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1999 to 2008. While adult lung transplantation grew significantly over the past decade, rates of heart-lung and pediatric lung transplantation have remained low. Since implementation of the lung allocation score (LAS) donor allocation system in 2005, decreases in the number of active waiting list patients, waiting times for lung transplantation and death rates on the waiting list have occurred. However, characteristics of recipients transplanted in the LAS era differed from those transplanted earlier. The proportion of candidates undergoing lung transplantation for chronic obstructive pulmonary disease decreased, while increasing for those with pulmonary fibrosis. In the LAS era, older, sicker and previously transplanted candidates underwent transplantation more frequently compared with the previous era. Despite these changes, when compared with the pre-LAS era, 1-year survival after lung transplantation did not significantly change after LAS inception. The long-term effects of the change in the characteristics of lung transplant recipients on overall outcomes for lung transplantation remain unknown. Continued surveillance and refinements to the LAS system will affect the distribution and types of candidates transplanted and hopefully lead to improved system efficiency and outcomes.

Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome.

Primary graft dysfunction (PGD) is a common early complication after lung transplantation. We conducted a retrospective cohort study of 334 recipients to evaluate the impact of PGD graded at 24, 48 and 72 h on the risk of bronchiolitis obliterans syndrome (BOS) development (stage 1) and progression (stages 2 and 3). We constructed multivariable Cox proportional hazards models to determine the risk of BOS attributable to PGD in the context of other potential risk factors including acute rejection, lymphocytic bronchitis and respiratory viral infections. All grades of PGD at all time points were significant risk factors for BOS development and progression independent of acute rejection, lymphocytic bronchitis and respiratory viral infections. Specifically, PGD grade 1 at T24 was associated with a relative risk of BOS stage 1 of 1.93, grade 2 with a relative risk of 2.29 and grade 3 with a relative risk of 3.31. Furthermore, this direct relationship between the severity of PGD and the risk of BOS persisted at all time points. We conclude that all grades of PGD at all time points are independent risk factors for BOS development and progression. Future strategies that might attenuate the severity of PGD may mitigate the risk of BOS.

Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism.

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge. The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE. The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (>or=0.1 ng x mL(-1)) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1-12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90-97)%. In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.

Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases.

BACKGROUND: Post-transplantation lymphoproliferative disease (PTLD) after lung transplantation has not been fully characterized. In previous studies, the incidence has varied substantially, and most cases have been reported during the first year after transplantation. The purpose of this study was to review our center's experience with PTLD and to analyze the pattern of disease and determinants of outcome. METHODS: Among 494 adult lung (n = 491) or heart-lung (n = 3) recipients, 30 cases of PTLD were retrospectively identified. The cases were classified by site(s) of involvement, histology and time of onset (early, < or =1 year, and late, >1 year after transplantation). The outcome of each case was ascertained, and risk factors for death were analyzed in a multivariate model. RESULTS: PTLD was identified in 30 (6.1%) of the recipients during 1,687 patient-years (median 2.8 years) of follow-up. The incidence density was 1.8 cases per 100 patient-years. Fourteen cases were diagnosed during the first year after transplantation, and 16 cases in subsequent years. The incidence density was significantly higher in the first year than in later years (3.3 cases/100 patient-years versus 1.3 cases/100 patient years; p <.008). Presentation in the thorax and involvement of the allograft were significantly more common in the early cases (thorax: 12 of 14, 86%; allograft: 9 of 14, 64%) than in the late cases (thorax: 2 of 16, 12%; allograft: 2 of 16, 12%). There was no difference in survival after the diagnosis of PTLD between the early and late cases, but survival time after diagnosis was significantly longer in cases with, than those without, allograft involvement (median 2.6 years vs 0.2 year, respectively; log rank p = 0.007). The presentation and pattern of organ involvement of PTLD after lung transplantation is related to the time of onset. CONCLUSIONS: Disease in the thorax and involvement of the allograft are common in the first year after transplantation, but other sites, especially the gastrointestinal tract, predominate later. PTLD that is confined to the allograft appears to have a somewhat better prognosis than disease that involves other sites.

Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery.

PURPOSE: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS). MATERIALS AND METHODS: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests. RESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83). CONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.

Outcome of bilateral lung volume reduction in patients with emphysema potentially eligible for lung transplantation.

OBJECTIVE: Between January 1993 and May 1998, we performed 200 consecutive bilateral lung volume reduction operations. After initial assessment, 99 of these patients were eligible for lung volume reduction and potentially eligible for immediate or eventual lung transplantation on the basis of age and absence of contraindications. All chose to proceed with lung volume reduction surgery. The outcomes of these 99 patients are reviewed to assess the consequences of proceeding with lung volume reduction surgery on patients potentially eligible for lung transplantation. METHODS: A retrospective study was performed with the use of a prospectively assembled computer database. RESULTS: The 61 men and 38 women were 55 +/- 7 years old at evaluation for lung volume reduction. Mean values for first second expired volume, total lung capacity, and residual volume were 24% +/- 8%, 141% +/- 19%, and 294% +/- 54% predicted. There were 4 operative deaths and 17 late deaths. Two-year and 5-year survival after evaluation for lung volume reduction are 92% and 75%. The 32 patients who have been listed for transplantation after lung volume reduction include 15 who have undergone transplantation, 14 who remain on the list, and 3 who have been removed from the list. All 15 transplant recipients survived transplantation and 3 have subsequently died of rejection or late infection. The 12 living recipients have a median post-transplantation follow-up of 1.7 years. The age at transplantation was 58 +/- 5 years with transplantation occurring 3.8 +/- 1.1 years after lung volume reduction. Sixteen of 99 patients underwent lower lobe volume reduction with an increased rate of listing (63%, P =.008) and transplantation (38%, P =.003) compared with patients undergoing upper lobe volume reduction. Patients listed for transplantation were younger, more impaired, and experienced less benefit from lung volume reduction than patients not yet listed for transplantation. CONCLUSIONS: The preliminary use of lung volume reduction in patients potentially suitable for transplantation does not appear to jeopardize the chances for subsequent successful transplantation.

Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease.

BACKGROUND: Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease. OBJECTIVE: To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease. DESIGN: Randomized, controlled, partially blinded equivalence trial. SETTING: 74 hospitals in 16 countries. PATIENTS: 900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism. INTERVENTIONS: Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization. MEASUREMENTS: Clinical end points assessed during a 3-month follow-up period. RESULTS: Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, -3.04% to 3.49%) for once-daily enoxaparin and -1.2% (CI, -4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group. CONCLUSIONS: Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease.

Cost for inpatient care of venous thrombosis: a trial of enoxaparin vs standard heparin.

BACKGROUND: Enoxaparin, a low-molecular-weight heparin administered to hospitalized patients once or twice daily, has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease. Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin, the overall cost of care for each of these 3 treatment strategies is unknown. METHODS: A cost minimization analysis of a 3-month, partially blinded, randomized, controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis. Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were randomly assigned to initial therapy with subcutaneous enoxaparin either once (n = 112) or twice (n = 123) daily, or with dose-adjusted intravenous unfractionated heparin (n = 104), followed by long-term oral anticoagulant therapy. Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning standard unit costs to counts of medical resources used by each patient in the clinical trial. RESULTS: Average total cost for the 3-month episode of care was similar across all 3 treatment regimens: once-daily dose of enoxaparin, $12,166 (95% confidence interval [CI], $10,744-$13,588); twice-daily dose of enoxaparin, $11,558 (95% CI, $10,201-$12,915); and unfractionated heparin, $12,146 (95% CI, $10,670-$12,622). Bootstrapped estimates and sensitivity analyses did not significantly change findings. CONCLUSIONS: There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin. Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions.

Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline.

OBJECTIVE: A panel was convened by the Health and Science Policy Committee of the American College of Chest Physicians to develop a clinical practice guideline on the medical and surgical treatment of parapneumonic effusions (PPE) using evidence-based methods. OPTIONS AND OUTCOMES CONSIDERED: Based on consensus of clinical opinion, the expert panel developed an annotated table for evaluating the risk for poor outcome in patients with PPE. Estimates of the risk for poor outcome were based on the clinical judgment that, without adequate drainage of the pleural space, the patient with PPE would be likely to have any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. Three variables, pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, were used in this annotated table to categorize patients into four separate risk levels for poor outcome: categories 1 (very low risk), 2 (low risk), 3 (moderate risk), and 4 (high risk). The panel's consensus opinion supported drainage for patients with moderate (category 3) or high (category 4) risk for a poor outcome, but not for patients with very low (category 1) or low (category 2) risk for a poor outcome. The medical literature was reviewed to evaluate the effectiveness of medical and surgical management approaches for patients with PPE at moderate or high risk for poor outcome. The panel grouped PPE management approaches into six categories: no drainage performed, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery (VATS), and surgery (including thoracotoiny with or without decortication and rib resection). The fibrinolytic approach required tube thoracostomy for administration of drug, and VATS included post-procedure tube thoracostomy. Surgery may have included concomitant lung resection and always included postoperative tube thoracostomy. All management approaches included appropriate treatment of the underlying pneumonia, including systemic antibiotics. Criteria for including articles in the panel review were adequate data provided for >/=20 adult patients with PPE to allow evaluation of at least one relevant outcome (death or need for a second intervention to manage the PPE); reasonable assurance provided that drainage was clinically appropriate (patients receiving drainage were either category 3 or category 4) and drainage procedure was adequately described; and original data were presented. The strength of panel recommendations on management of PPE was based on the following approach: level A, randomized, controlled trials with consistent results or individual randomized, controlled trial with narrow confidence interval (CI); level B, controlled cohort and case control series; level C, historically controlled series and case series; and level D, expert opinion without explicit critical appraisal or based on physiology, bench research, or "first principles." EVIDENCE: The literature review revealed 24 articles eligible for full review by the panel, 19 of which dealt with the primary management approach to PPE and 5 with a rescue approach after a previous approach had failed. Of the 19 involving the primary management approach to PPE, there were 3 randomized, controlled trials, 2 historically controlled series, and 14 case series. The number of patients included in the randomized controlled trials was small; methodologic weaknesses were found in the 19 articles describing the results of primary management approaches to PPE. The proportion and 95% CI of patients suffering each of the two relevant outcomes (death and need for a second intervention to manage the PPE) were calculated for the pooled data for each management approach from the 19 articles on the primary management approach. (ABST

Outcome of patients with cystic fibrosis awaiting lung transplantation.

Cystic fibrosis is a common indication for lung transplantation. Under the current organ allocation system, donor lungs are distributed to patients based solely on their accrued waiting time, and the death rate on the waiting list has been high. Physiologic parameters have been used to guide the referral, but risk factors for death while awaiting transplantation have not been well defined. This study aimed to identify factors at the time of evaluation that were associated with death on the waiting list. A consecutive cohort of 146 patients with cystic fibrosis who were listed for lung transplantation was retrospectively reviewed. Characteristics of patients who died awaiting transplantation were compared with those of patients who survived until transplantation or the end of the study. Thirty-seven patients died while waiting, 76 underwent transplantation, and 33 were alive and still waiting. Actuarial survival rates for the entire cohort were 81% at 1 yr, 67% at 2 yr, and 59% at 3 yr. Although a multivariate Cox proportional hazards model (chi(2) = 29.6; p < 0.001) identified shorter six-minute walk distance (50 m increments; RR, 0.69; 95% CI, 0.57 to 0.84), higher systolic pulmonary artery pressure (5 mm Hg increments; RR, 1.41; 95% CI, 1.11 to 1.80), and diabetes mellitus (RR, 1.57; 95% CI, 1.06 to 2.32) as significant risk factors for death on the waiting list, these factors and other features overlapped considerably between the group of patients who died waiting and the group who lived until transplantation or the end of the study. The transplant evaluation selects a rather homogeneous cohort of patients for the waiting list. Unless outcome on the waiting list can be reliably predicted, establishing criteria to allocate donor lungs according to medical urgency may not be feasible.