Propensity Score-adjusted Hazard Ratio Research Articles

Prophylactic funnel mesh to prevent parastomal hernia in permanent end colostomy: A retrospective cohort study.

This study assessed the impact of a prophylactic, 3D funnel-shaped intraperitoneal mesh on the rate of parastomal hernia after abdominoperineal rectum resection with permanent end colostomy. Data from 76 patients receiving permanent end colostomy after abdominoperineal rectum resection between 2013 and 2018 were collected retrospectively. Occurrences of parastomal hernia and reoperation rate due to parastomal hernia in patients with and without a prophylactic mesh were compared by univariate, multivariate, and propensity score-adjusted analyses. Twenty-two (28.9%) of the 76 included patients received a prophylactic mesh. The mean follow-up was 39.3±23.8months. Mesh implantation reduced the incidence of parastomal hernia to 9.1% (n=2) compared to 42.6% (n=23) in patients without a prophylactic mesh. The propensity score-adjusted hazard ratio (HR) was 0.14 (95% confidence interval (CI): 0.04-0.48, p=0.001). No reoperations due to parastomal hernia were needed in patients who received a prophylactic mesh, while nine patients without mesh (16.7%) required parastomal hernia repair (HR=0.09, 95% CI: 0.00-1.76, p=0.015). Mesh implantation was not associated with increased short-term morbidity (Clavien-Dindo grade>2, 31.8% vs. 40.7%, p=0.468) or 30-day mortality (4.5% vs. 3.8%, p=1.000). Prophylactic implantation of a 3D funnel-shaped intraperitoneal mesh is a safe and effective method to prevent parastomal hernia in patients requiring permanent end colostomy. Mesh placement significantly reduces reoperations due to parastomal hernia.

FOLFOXIRI-Bevacizumab or FOLFOX-Panitumumab in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Propensity Score-Based Analysis.

Doublets plus anti-epidermal growth factor receptors (EGFRs) are the preferred upfront option for patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Initial therapy with FOLFOXIRI-bevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRI-bevacizumab versus doublets plus anti-EGFRs is available in left-sided RAS/BRAF wild-type mCRC. We selected patients with left-sided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score-based analysis was performed to compare FOLFOXIRI-bevacizumab with FOLFOX-panitumumab. A total of 185 patients received FOLFOX-panitumumab and 132 received FOLFOXIRI-bevacizumab. Median progression-free survival (PFS) and median overall survival (OS) were 13.3 and 33.1 months in the FOLFOXIRI-bevacizumab group compared with 11.4 and 30.3 months in the FOLFOX-panitumumab group (propensity score-adjusted hazard ratio (HR) for PFS, 0.82; 95% confidence interval (CI), 0.64-1.04; p = .11; propensity score-adjusted HR for OS, 0.80; 95% CI, 0.59-1.08; p = .14). No significant differences in overall response rate and disease control rate were observed. A statistically nonsignificant difference in favor of FOLFOXIRI-bevacizumab was observed for OS after secondary resection of metastases. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001). Although randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-type mCRC. A propensity score-based analysis of five trials was performed to compare FOLFOX-panitumumab versus FOLFOXIRI-bevacizumab in left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No significant differences were observed, but FOLFOXIRI-bevacizumab achieved numerically superior survival outcomes versus FOLFOX-panitumumab. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group. These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients' preference and potential impact on quality of life.

Closing the gap: Contribution of surgical best practices to outcome differences between high- and low-volume centers for lung cancer resection.

BackgroundClinical outcomes for resected early‐stage non‐small cell lung cancer (NSCLC) are superior at high‐volume facilities, but reasons for these differences remain unclear. Understanding these differences and optimizing outcomes across institutions are critical to the management of the increasing incidence of these cases. We evaluated the extent to which surgical best practices account for resected early‐stage NSCLC outcome differences between facilities according to case volume.MethodsWe performed a retrospective cohort study for clinical stage 1 or 2 NSCLC undergoing surgical resection from 2004 to 2013 using the National Cancer Database (NCDB). Surgical best practices (negative surgical margins, lobar or greater resection, lymph node (LN) dissection, and examination of > 10 LNs) were compared between the highest and lowest quartile volumes.ResultsA total of 150,179 patients were included in the cohort (89% white, 53% female, median age 68 years). In a multivariate model, superior overall survival (OS) was observed at highest volume centers compared to lowest volume centers (hazard ratio (HR) = 0.89; 95% CI, 0.82‐0.96; P = .002). After matching for surgical best practices, there was no significant OS difference (HR = 0.95; 95% CI, 0.87‐1.05; P = .32). Propensity score‐adjusted HR estimates indicated that surgical best practices accounted for 54% of the numerical OS difference between low‐volume and high‐volume centers. Each surgical best practice was independently associated with improved OS (all P ≤ .001).ConclusionQuantifiable and potentially modifiable surgical best practices largely account for resected early‐stage NSCLC outcome differences observed between low‐ and high‐volume centers. Adherence to these guidelines may reduce and potentially eliminate these differences.

Elderly Patients with Moderate Chronic Ischemic Mitral Regurgitation: Coronary Artery Bypass Grafting Alone or Concomitant Mitral Annuloplasty?

Background An increasing number of elderly patients with ischemic mitral regurgitation (IMR) are referred for coronary artery bypass grafting (CABG). However, data about the management of elderly patients with moderate IMR are scanty. This study evaluates the impacts of two surgical approaches (CABG alone or concomitant mitral annuloplasty (MAP)) on in-hospital and midterm outcomes, to attempt to determine an appropriate treatment option for elderly patients with moderate chronic IMR. Methods All eligible patients over 65 years of age were included and were entered into either a MAP group (patients undergoing CABG plus MAP, n = 96) or a CABG group (patients receiving CABG alone, n = 104). Baseline and surgical characteristics were analyzed, and in-hospital and midterm outcomes between groups were compared after propensity score-matching (1 : 1). Results Using propensity score-matching, 82 pairs of patients were successfully established in a 1 : 1 ratio. No significant differences between the two matched groups were found regarding surgical mortality (4.9% vs. 1.2%, p=0.173) and major postoperative morbidity. 150 patients (76 in the MAP group and 74 in the CABG group) received regular follow-up visit with the median duration of 37 months. Compared with the CABG group, the MAP group received a similar overall survival but a better recurrent MR-free survival (stratified log-rank p, 0.492 and < 0.001, respectively). Using Cox regression, the MAP group as compared with the CABG group did not affect midterm survival probability (propensity score-adjusted hazard ratio, 0.854; 95% confidence interval, 0.571–2.729, p=0.630). Additionally, patients in the MAP group had a significantly lower ratio of NYHA class III-IV at the latest follow-up by comparison with patients in the CABG group (19.7% vs. 35.5%, p=0.033). Conclusion Compared with CABG alone, concomitant mitral annuloplasty is associated with improved midterm outcomes (including reduced IMR recurrence and improved cardiac functional class) but shares similar surgical mortality and major postoperative morbidity and may be a promising treatment option for elderly patients with moderate chronic IMR.

Association of an Early Intervention Service for Psychosis With Suicide Rate Among Patients With First-Episode Schizophrenia-Spectrum Disorders

Patients with schizophrenia have a substantially higher suicide rate than the general public. Early intervention (EI) services improve short-term outcomes. However, little is known about the association of EI with suicide reduction in the long term. To examine the association of a 2-year EI service with suicide reduction in patients with first-episode schizophrenia-spectrum (FES) disorders during 12 years and the risk factors for early and late suicide. This historical control study compared 617 consecutive patients with FES who received the 2-year EI service in Hong Kong between July 1, 2001, and June 30, 2003, with 617 patients with FES who received standard care (SC) between July 1, 1998, and June 30, 2001, matched individually. Clinical information was systematically retrieved for the first 3 years of clinical care for both groups. The details of death were collected up to 12 years from presentation to the services. Data analysis was performed from October 30, 2016, to August 18, 2017. Suicide rate during 12 years was the primary measure. The association of the EI service with the suicide rates during years 1 through 3 and years 4 through 12 were explored separately. The main analysis included 1234 patients, with 617 in each group (mean [SD] age at baseline, 21.2 [3.4] years in the EI group and 21.3 [3.4] years in the SC group; 318 male [51.5%] in the EI group and 322 [52.2%] in the SC group). The suicide rates were 7.5% in the SC group and 4.4% in the EI group (McNemar χ2 = 5.55, P = .02). Patients in the EI group had significantly better survival (propensity score-adjusted hazard ratio, 0.57; 95% CI, 0.36-0.91; P = .02), with the maximum association observed in the first 3 years. The number of suicide attempts was an indicator of early suicide (1-3 years). Premorbid occupational impairment, number of relapses, and poor adherence during the initial 3 years were indicators of late suicide (4-12 years). This study suggests that the EI service may be associated with reductions in the long-term suicide rate. Suicide at different stages of schizophrenia was associated with unique risk factors, highlighting the importance of a phase-specific service.

FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials

FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013}. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. NCT01219920 and NCT00719797.

Off-pump coronary artery bypass grafting versus optimal medical therapy alone: effectiveness of incomplete revascularization in high risk patients.

BackgroundGeriatric patients with multivessel coronary artery disease (CAD) are a challenging group to treat; these cases elicit discussion within heart teams regarding the actual benefit of undertaking major surgery on these patients and often lead to abandon the surgical option. Percutaneous procedures represent an important option, but coronary anatomy may be unfavorable. Off-pump coronary artery bypass (OPCAB) provides good quality graft on left anterior descending (LAD) without exposing the patient to cardiopulmonary bypass, and might be the ideal choice in patients with multiple comorbidities, not eligible to percutaneous or on-pump procedures. The objective of this study was to compare survival during a mid-term follow-up in high-risk patients with no percutaneous alternative, either treated with OPCAB or discharged in medical therapy.MethodsWe retrospectively evaluated from June 2008 to June 2013, 83 high-risk patients with multivessel CAD were included: 42 were treated with incomplete off-pump revascularization using left internal mammary artery (LIMA) on LAD; 41 were discharged in optimal medical therapy (OMT), having refused surgery. Follow-up ended in March 2015, with a telephonic interview. Primary endpoint was survival from all-cause mortality; secondary endpoints were survival from cardiac-related mortality and freedom from non-fatal major adverse cardiac events (MACEs).ResultsDuring follow up, 11 deaths in OPCAB group and 27 deaths in OMT group occurred. Death was due to cardiac factors in 6 and 15 patients, respectively. MACEs were observed in 6 patients in OPCAB group and in 4 patients in OMT group. With regards to survival from all-cause mortality, patients who underwent OPCAB survived more than those discharged in OMT (Log Rank < 0.001), and OMT group carries a propensity score-adjusted hazard ratio of 3.862 (P < 0.001). With regards to survival from cardiac-related events, patients who underwent OPCAB survived more than those discharged in OMT (Log Rank = 0.002), and OMT group carries a propensity score-adjusted hazard ratio of 3.663 (P = 0.010). There is no statistically significant difference concerning freedom from MACEs (Log Rank = 0.273).ConclusionsFor high-risk patients with multivessel CAD, not eligible to on-pump complete revascularization surgery or percutaneous procedures, incomplete revascularization with OPCAB LIMA-on-LAD offers benefits in survival when compared to OMT alone.

Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study

The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007. Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group). In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings. Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.

Long-term clinical outcome after surgical or percutaneous coronary revascularization in hemodialysis patients

Background: Although revascularization by coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) has been widely performed in hemodialysis (HD) patients who are at the highest risk of cardiovascular disease, there have been limited data which procedure should be optimized. We investigated long-term clinical outcome after CABG or PCI including drug-eluting stent (DES) implantation in HD patients. Methods: A total 997 maintenance HD patients electively undergoing coronary revascularization with either CABG or PCI were enrolled. Of these patients, 210 patients underwent CABG and 787 patients underwent PCI (345 with DES implantation). They were followed up to 10-year, and the incidence of major adverse cardiovascular events (MACE) as a composite endpoint including all-cause death, non-fatal myocardial infarction (MI), stroke, and target lesion revascularization (TLR) were analyzed. To reduce the selection bias between the procedures, adjusting for propensity score with all baseline covariates was also performed. Results: Prevalence of diabetes, multi-vessel disease, left main trunk lesion and left ventricular ejection fraction < 0.4 were higher in patients undergoing CABG than PCI. The rate of 30-day mortality was significantly higher in CABG group compared to PCI group (4.8% vs. 1.9%, p=0.018). During follow-up period (mean 52±39 months), 484 MACEs (death:325, MI:45, stroke:67, and TLR:274) occurred. 10-year freedom rate was higher in CABG group compared to PCI group for MACE (49.6% vs. 32.4%, p=0.0013) and for TLR (83.4% vs. 56.0%, p<0.0001), respectively. Propensity score-adjusted hazard ratio (HR) was 0.68 [95% confidence interval (CI) 0.53-0.87, p=0.0025] for MACE and 0.26 (95% CI 0.69-1.25, p<0.0001) for TLR, respectively. On the other hand, the 10-year survival rate was comparable (57.4% vs. 52.1%, p=0.65) between two groups. As a landmark analysis, adjusted HR of death was higher during 6 months after CABG compared to PCI (2.33, 95% CI 1.36-3.98, p=0.0020), but lower after 6 months onward (0.65, 95% CI 0.45-0.94, p=0.021). When compared to DES group, CABG still had advantage for TLR (HR 0.39, 95% CI 0.24-0.65, p=0.0003), however, had even for MACE (HR 0.88, 95% CI 0.67-1.16, p=0.37). Conclusion: CABG might have totally clinical advantage compared to PCI even though the survival rate was similar after these procedures.

CC5-05: Comparative Safety of Infliximab and Etanercept on the Risk of Serious Infections - Does the Association Vary By Patient Characteristics?

Background/AimsInfliximab, a chimeric monoclonal anti-TNF? antibody, has been found to increase the risk of serious infections compared with the TNF receptor fusion protein etanercept in some studies. It is unclear whether the risk varies by patient characteristics. We conducted a study to address this question.MethodsWe identified members of Kaiser Permanente Northern California who initiated infliximab (n=793) or etanercept (n=2,692) in 1997–2007. Using a Cox model, we estimated the propensity score-adjusted hazard ratio (HR) and 95% confidence interval (CI) of serious infections requiring hospitalization or opportunistic infections comparing infliximab with etanercept following treatment initiation. We estimated the stratum-specific HRs by age ( =65 years), sex, race/ethnicity (Non- Hispanic White, African-American, Hispanic, Asian American, Native American, and other/unknown), body mass index ( =25 kg/m2), and smoking status (non, past, and current smokers); and performed likelihood ratio tests to examine whether the HR differed by these patient characteristics.ResultsThe crude incidence rate of serious infections per 100 person-years was 5.4 (95% CI: 3.8, 7.5) in patients =65 years during the first three months following treatment initiation. Compared with etanercept, the adjusted HR during this period was elevated for infliximab in patients =65 years (HR 0.94; 0.41, 2.13). The test for homogeneity was marginally statistically significant (p-value=0.06). Findings did not suggest that the HR varied by other patient characteristics examined.DiscussionAn increased risk of serious infections associated with infliximab relative to etanercept did not appear to be modified by patients’ sex, race/ethnicity, body mass index, or smoking status. There was an indication that the increased risk might vary by age. Additional studies are warranted to verify or refute this finding.

Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered. To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF. Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry. All-cause mortality. In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001). Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

Utilization patterns and patient outcomes associated with use of rescue therapies in acute lung injury*

To investigate the practice patterns and clinical outcomes associated with use of rescue therapies in patients with acute lung injury. Secondary analysis of multicentered, randomized, controlled trial data from the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Intensive care units of Acute Respiratory Distress Syndrome Clinical Trials Network centers across the United States. Subjects enrolled in six Acute Respiratory Distress Syndrome Clinical Trials Network trials occurring between 1996 and 2005. None. One hundred sixty-six of 2632 (6.3%) subjects received rescue therapy, defined as prone positioning (97 of 166 [58%]), inhaled vasodilators (47 of 166 [28%]), high-frequency ventilation (12 of 166 [7%]), or extracorporeal membrane oxygenation (10 of 166 [6%]). Use of inhaled vasodilators increased whereas use of prone position decreased over time (p for trend = 0.04 and 0.0013, respectively). Multivariate predictors for use of rescue therapy included age (odds ratio per 10 yrs and 95% confidence interval: 0.88; 0.78-0.99; p = .049), positive end-expiratory pressure (odds ratio per 5-cm H2O increase: 1.33; 95% confidence interval, 1.05-1.69; p = .019), Pao2/Fio2; odds ratio per 5-cm H2O increase: 0.98; 95% confidence interval, 0.96-0.99; p = .017), peak airway pressure (odds ratio per 5-cm H2O increase: 1.11; 95% confidence interval, 1.001-1.237; p = .047), and study order (odds ratio per subsequent Acute Respiratory Distress Syndrome Clinical Trials Network study: 1.21; 95% confidence interval, 1.03-1.41; p = .02). Cox proportional hazards analysis of propensity score-matched subjects showed no difference in survival for those who received rescue therapy vs. those who did not (hazard ratio for death after rescue therapy or index date, 1.10; 95% confidence interval, 0.67-1.78; p = .72). No differences in survival were found between those who received prone positioning vs. inhaled vasodilators (propensity score-adjusted hazard ratio for prone 0.87; 95% confidence interval, 0.86-2.10; p = .76). Rescue therapies are utilized in younger patients with more severe oxygenation deficits. Patterns of rescue therapy utilization appear to be changing over time. Within the limits of an observational study design, we did not find evidence of a survival benefit with use of rescue therapies in acute lung injury.

Long-Term Outcome of Alcohol Septal Ablation in Patients With Obstructive Hypertrophic Cardiomyopathy

Background— The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy. Methods and Results— Ninety-one consecutive patients (aged 54±15 years) with obstructive hypertrophic cardiomyopathy underwent ASA. Primary study end point was a composite of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary end points were noncardiac death and other nonfatal complications. Outcomes of ASA patients were compared with 40 patients with hypertrophic cardiomyopathy who underwent septal myectomy. During 5.4±2.5 years, primary and/or secondary end points were seen in 35 (38%) ASA patients of whom 19 (21%) patients met the primary end point. The 1-, 5-, and 8-year survival-free from the primary end point was 96%, 86%, and 67%, respectively in ASA patients versus 100%, 96%, and 96%, respectively in myectomy patients during 6.6±2.7 years (log-rank, P =0.01). ASA patients had a ≈5-fold increase in the estimated annual primary end point rate (4.4% versus 0.9%) compared with myectomy patients. In a multivariable model including a propensity score, ASA was an independent predictor of the primary end point (unadjusted hazard ratio, 5.2; 95% CI, 1.2 to 22.1; P =0.02 and propensity score-adjusted hazard ratio, 6.1; 95% CI, 1.4 to 27.1; P =0.02). Conclusions— This study shows that ASA has potentially unwanted long-term effects. This poses special precaution, given the fact that ASA is practiced worldwide at increasing rate. We recommend myectomy as the preferred intervention in patients with obstructive hypertrophic cardiomyopathy.

The Risk of Stent Thrombosis in Patients With Acute Coronary Syndromes Treated With Bare-Metal and Drug-Eluting Stents

We aimed to evaluate the risk of definite stent thrombosis with bare-metal stents (BMS) and drug-eluting stents (DES) in patients treated for acute coronary syndromes. Acute coronary syndromes (ACS) have been reported as increasing the risk for stent thrombosis. Between January 2000 and December 2005, 5,816 consecutive patients underwent percutaneous coronary intervention for de novo lesions with a single stent type. These patients consisted of 3 sequential groups of BMS (n = 2,248), sirolimus-eluting stents (n = 822) and paclitaxel-eluting stents (n = 2,746). In total, 3,485 patients presented with an ACS. After a median follow-up of 1,394 days, patients with ACS had a definite stent thrombosis rate of 2.5% versus 1.0% in patients with stable angina (propensity score-adjusted hazard ratio [HR]: 2.80, 95% confidence interval [CI]: 1.72 to 4.56). ACS patients had a higher risk of early and late stent thrombosis, although the increased risk of very late stent thrombosis was only present in ACS patients treated with DES. In stable patients, any stent thrombosis resulted in a significant increase in mortality (adjusted HR: 4.0, 95% CI: 1.7 to 9.3), although this was particularly evident for late or very late stent thrombosis; in contrast only early stent thrombosis significantly increased mortality in patients with acute coronary syndrome patients (adjusted HR: 2.0, 95% CI: 1.0 to 4.1). Patients with acute coronary syndromes are at higher risk of early and late stent thrombosis with either BMS or DES, although very late stent thrombosis seems to be uniquely associated with DES. The clinical sequelae of late and very late stent thrombosis are more pronounced in stable patients.

Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction

Background— Primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction with bare metal stents (BMS) is well established, while randomized trials suggest equivalent safety and reduced repeat revascularization with drug-eluting stents (DES) in this setting. However, long-term data on DES in PPCI is lacking, especially in those ineligible for inclusion in randomized trials. Our aim was to investigate the long-term outcomes of unselected patients undergoing PPCI with BMS and DES. Methods and Results— We analyzed all patients (n=1738) undergoing PPCI for a de novo lesion in our institution from 2000 to 2005. Patients from 3 sequential consecutive cohorts of BMS (n=531), sirolimus-eluting (SES, n=185) or paclitaxel-eluting stents (PES, n=1022) were included. The median duration of follow-up was 1185 days (interquartile range, 746 to 1675). There were no differences in all-cause mortality or repeat revascularization between DES and BMS, although there was a nonsignificant trend toward improved survival with SES compared with both BMS (propensity score-adjusted hazard ratio, 0.63; [95%CI, 0.33 to 1.18]) and PES (hazard ratio, 0.71; [95% CI, 0.40 to 1.26]). SES were associated with lower rates of the composite end point of all-cause death, nonfatal myocardial infarction, or target vessel revascularization (hazard ratio, 0.62; 95%CI, 0.40 to 0.96) when compared with PES. Very late stent thrombosis only occurred in the DES groups. Conclusions— Although DES are not associated with an increase in adverse events compared with BMS when used for PPCI, neither DES reduced repeat revascularizations. Appropriately powered randomized trials with hard clinical end points and an “all-comer” design are required to further assess the benefit of DES in PPCI.

Outcomes After Sirolimus- and Paclitaxel-Eluting Stent Implantation in Patients With Insulin-Treated Diabetes Mellitus

Insulin-treated diabetic patients undergoing drug-eluting stent implantation are prone to high rates of adverse cardiac events. The efficacy of the sirolimus- (SES) and paclitaxel-eluting stent (PES) in this population was analyzed. Registry data for 434 consecutive patients with insulin-treated diabetes who underwent SES or PES implantation were analyzed. The end point, major adverse cardiac events (MACEs) at 1 year, was high for patients with SESs and PESs (20.6% vs 20.2%; p=0.91). Cox regression and propensity analysis were used to compare outcomes. The adjusted hazard ratio (HR) for MACEs according to stent type (Cox model) was 1.0 (95% confidence interval [CI] 0.64 to 1.76, p=0.82). The propensity score-adjusted (C statistic=0.66) HR was 0.95 (95% CI 0.56 to 1.61, p=0.84). Stent thrombosis rates were relatively high at 2.0% for SESs and 1.5% for PESs (p=0.49). The propensity score-adjusted HR for stent thrombosis was 2.7 (95% CI 0.31 to 23.6, p=0.37). In conclusion, SESs and PESs are similarly efficacious in insulin-treated diabetic patients. The high MACE and stent thrombosis rates are of concern. Additional studies in this group of patients are required to determine the optimal mode of revascularization and minimize the overall stent thrombosis rate.