1-year Hazard Ratio Research Articles

Outcomes associated with dual antiplatelet therapy after myocardial infarction in patients with aortic stenosis

BackgroundAcquired loss of the largest von Willebrand factor multimers is a common hemostatic disturbance in patients with aortic valve stenosis (AS), resulting in impaired platelet adhesion and increased bleeding risk. AS is also associated with atherosclerosis and myocardial infarction (MI). Our aim was to study the clinical outcomes associated with AS in MI patients treated with dual antiplatelet therapy (DAPT) in a nationwide hospital-based register study. MethodsBased on nationwide hospital discharge registers from Sweden (2005–2010) and Denmark (2005–2015), we calculated 1-year incidence rates and hazard ratios of bleeding, recurrent MI, and all-cause mortality in MI patients with and without AS treated with DAPT. Results from both countries were also combined in a meta-analysis. ResultsWe included 50,460 MI patients from Sweden and 50,307 MI patients from Denmark, of which 3% had AS. The bleeding rates (per 100 person-years) in Sweden and Denmark were 3.2 and 3.3 among patients without AS vs. 9.2 and 8.3 among patients with AS. All-cause mortality rates were 7.1 vs. 28.7 in Sweden and 5.8 vs. 30.7 in Denmark among patients without and with AS, respectively. Patients with AS had an increased risk of bleeding, recurrent MI and all-cause mortality. Combined results from both countries were similar for bleeding (hazard ratio 1.59 [0.98–2.59]), recurrent MI (1.78 [1.25–2.54]), and all-cause mortality (1.76 [1.26–2.47]). ConclusionAS was associated with an increased risk of bleeding, recurrent MI and mortality after MI when treated with DAPT. Individualized selection of antiplatelet therapy may be warranted in this high-risk population.

Infectious complications after heart transplantation in patients screened with gene expression profiling.

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection. The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp. The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp. In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

Liver Transplant Survival Index for Patients with Model for End-Stage Liver Disease Score ≥ 35: Modeling Risk and Adjusting Expectations in the Share 35 Era

The Share 35 policy for liver allocation prioritizes patients with Model for End-Stage Liver Disease (MELD) scores ≥ 35 for regional sharing of liver allografts. To better assess donor-recipient interactions and inform expectations, this study identified factors affecting graft survival independent of MELD score and derived a risk index for transplantation in the MELD ≥ 35 population. The United Network for Organ Sharing (UNOS) STAR database was evaluated for deceased donor liver transplants with recipients' MELD ≥ 35, between January 2006 and June 2016. Data were randomly split into test and validate cohorts. Four individual models of graft survival spanning 90 days to 5 years were evaluated with univariate and multivariate Cox proportional hazards analyses against donor- and recipient-specific characteristics. Significant factors were compiled to generate the Liver Transplant Survival Index (LTSI-35), and survival analyses were performed. Five risk groups (very low, low, moderate, high, and severe) were identified, with 1-year graft survival rates of 90.8% ± 0.2%, 89.3% ± 0.3%, 85.0% ± 0.3%, 79.8% ± 0.3%, and 70.3% ± 0.4% (p < 0.001 across groups), respectively. The greatest risk of graft loss was associated with donation after circulatory death (DCD) donors (1-year hazard ratio [HR]= 1.61 [95% CI 1.26 to 2.05], p= 0.001), recipients' requiring ventilator support (HR 1.32 [95% CI 1.17 to 1.51], p < 0.001), and recipient portal vein thrombosis (HR 1.21 [95% CI 1.03 to 1.42], p= 0.003). Subgroup analysis revealed increased risk of graft loss with graft macrosteatosis ≥ 30% on pre-donation biopsy at 90 days (HR 1.64 [1.33 to 1.99], p < 0.001). The LTSI-35 identifies risk factors for graft loss in a high-MELD population which, when combined, may portend worse outcomes. The LTSI-35 may be used to influence donor selection, organ allocation, and to inform expectations for allograft survival.

Survival Impact of Locoregional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancers in a Large Multicentric Cohort Study: A Propensity Score-Matched Analysis

Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial. The aim of our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination. We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both. LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger (p < 0.0001) and were more likely to have only one metastatic site (p < 0.0001) or bone-only metastases (p < 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55-0.76, p < 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9months, p < 0.001) and HER2-positive tumors (77.2 vs. 52.6months, p = 0.008), but not in triple-negative tumors (19 vs. 18.6months, p = 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients (p < 0.001). LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.

Preadmission use of glucocorticoids and risk of cardiovascular events in patients with ischemic stroke

Essentials The risk of thrombosis among ischemic stroke patients using glucocorticoids is unknown. We examined the risk of thrombosis in 98 487 ischemic stroke patients, by glucocorticoid use. Myocardial infarction and venous thromboembolism risk was increased in glucocorticoid users. Hemorrhagic stroke risk was lower and recurrent ischemic stroke the same in glucocorticoid users. SUMMARY: Background Glucocorticoid users have a high mortality rate following stroke, but the underlying clinical pathways are poorly understood. Objectives To examine the risk of cardiovascular events among ischemic stroke patients using glucocorticoids. Methods We conducted a nationwide population-based cohort study by using medical registries in Denmark. We identified all patients hospitalized with a first-time ischemic stroke (2004-2013). We categorized glucocorticoid use into current use (last prescription redemption ≤ 90 days before admission), former use, and non-use. With non-users as reference, we studied the risks of recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction and venous thromboembolism associated with glucocorticoid use. Comorbidity and comedication-adjusted 1-year hazard ratios (aHRs) with 95% confidence intervals (CIs) were computed on the basis of Cox regression analysis. Results We identified 98 487 patients with a first-time (index) ischemic stroke. After the index stroke, the 1-year cumulative incidence of recurrent ischemic stroke was 16.4% among current glucocorticoid users, whereas risks were lower for hemorrhagic stroke (0.46%), myocardial infarction (1.35%), and venous thromboembolism (0.98%). Among current glucocorticoid users, aHRs were increased for myocardial infarction (1.32, 95% CI 0.98-1.76) and venous thromboembolism (1.39, 95% CI 0.99-1.94), whereas the risk of hemorrhagic stroke was reduced (aHR 0.60, 95% CI 0.38-0.93). There was no association with recurrent ischemic stroke (aHR 1.01, 95% CI 0.94-1.09). Conclusions During the first year after ischemic stroke, current glucocorticoid use was associated with moderately increased risks of myocardial infarction and venous thromboembolism, and a lower risk of hemorrhagic stroke, whereas the risk of recurrent ischemic stroke was not affected.

Bladder preservation approach versus radical cystectomy for high-grade non-muscle-invasive bladder cancer: a meta-analysis of cohort studies

BackgroundHigh-grade non-muscle-invasive bladder cancer is superficial; nonetheless, it is an aggressive cancer. Proper management strategy selection following transurethral resection between bladder preservation (BP) and radical cystectomy (RC) could result in delayed or excessive treatment. Hence, selecting the optimal treatment modality remains controversial to date.MethodsWe searched MEDLINE, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, and Wanfang database through 12 April 2018. Quality and publication bias were assessed using the Newcastle-Ottawa Scale and Begg’s/Egger’s test. We collected 2-year, 5-year, 10-year, and 15-year survival rate and hazard ratio (HR) for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Using the Review Manager 5.2 software, we used the odds ratio (OR) of specific years and HR for meta-analysis. Subgroup analysis was performed by the original tumor state, radical cystectomy timing, bladder preservation modality, and age.ResultsIn total, 11 cohorts with 1735 patients were selected for the meta-analysis. All OR of OS supported BP as a better treatment option; however, all OR of PFS had no significant differences. As for CSS, only the 15-year OR reflected a statistical significance preferring RC. Subgroup analysis showed that BP is more appropriate for patients older than 65 and G3 tumor. Limited data demonstrated that late RC (> 3 months) is more effective compared to early RC (< 3 months) and intravesical Bacillus Calmette–Guerin was not statistically different from that of RC. The mixed BP modalities were significantly better compared to RC in OS and worse in CSS, with both having a very low evidence strength.ConclusionsBP is a superior treatment modality compare to RC, especially for older patients and T1G3 or lower grade tumors. However, the superior BP modality was unclear. Conversely, RC could be a better option for younger patients. More specifically, late RC may be more beneficial but had a very-low-level of evidence. Quality of life should be considered equal to survival outcome; hence, post-treatment follow-up needs to be performed. Prospective randomized studies should be performed to overcome the limitations of this meta-analysis study.RegistrationRegistration ID is CRD42018093491.

Trends, correlates, and survival of infants with congenital diaphragmatic hernia and its subtypes.

To identify the live-birth prevalence, trends, correlates, and neonatal and 1-year survival rates of congenital diaphragmatic hernia. Using a population-based, retrospective cohort study design, we examined 1,025 cases of congenital diaphragmatic hernia from the 1998-2012 Florida Birth Defects Registry. We used Poisson and joinpoint regression models to compute prevalence ratios and temporal trends, respectively. Kaplan-Meier survival curves and Cox proportional hazards regression were used to describe neonatal and 1-year survival and estimate hazard ratios representing the predictors of infant survival. The birth prevalence of congenital diaphragmatic hernia was 3.19 per 10,000 live births (95% confidence interval [CI]: 3.00-3.39); there was a 4.2% yearly increase among multiple cases only. Among all cases, maternal education less than high school (prevalence ratio: 1.25, 95% CI: 1.02-1.53), high school/associate degree/GED (prevalence ratio: 1.15, 95% CI: 1.01-1.32), multiple birth (prevalence ratio: 1.38, 95% CI: 1.05-1.81), and male sex (prevalence ratio: 1.18, 95% CI: 1.05-1.32) were associated with increased risk for congenital diaphragmatic hernia. The 24-hr, neonatal, and 1-year survival rates were 93.6%, 79.8%, and 71.2%, respectively. The highest hazard ratio of 17.87 (95% CI: 1.49-213.82) was observed for neonatal mortality among cases associated with chromosomal anomalies and born <37 weeks at < 1,500 g. Among isolated cases, multiple birth (hazard ratio: 0.41, 95% CI: 0.20-0.86) was associated with decreased 1-year mortality. Low maternal education and multiple birth may be linked to congenital diaphragmatic hernia. The trends in prevalence, epidemiologic correlates, and predictors of early survival can differ between congenital diaphragmatic hernia subtypes-isolated, multiple, and chromosomal.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Diabetes and ischaemic stroke outcome.

To compare all-cause mortality, stroke recurrence and functional outcomes in people who have experienced stroke, with and without diabetes. We captured data on population-based ischaemic strokes (2006-2012) in Nueces County, Texas. Data were collected from participant interviews and medical records. Differences in cumulative mortality and stroke recurrence risk by diabetes status were estimated at 30 days and 1 year using Cox models. Differences in 90-day functional outcomes (activities of daily living/instrumental activities of daily living score: range 1-4; higher scores worse) by diabetes status were assessed using Tobit regression. Effect modification by ethnicity was examined. There were 1301 ischaemic strokes, 46% with history of known diabetes. The median (interquartile range) age was 70 (58-81) years and 61% were Mexican American. People with diabetes were younger and more likely to be Mexican American compared with those without diabetes. After adjustment, diabetes predicted mortality (30-day hazard ratio 1.44, 95% CI 0.97-2.12; 1-year hazard ratio 1.47, 95% CI 1.09-1.97) but not stroke recurrence (1-year hazard ratio 1.27, 95% CI 0.78-2.07). People with diabetes had a worse functional outcome score that was explained by cardiovascular risk factors and pre-stroke factors. Diabetes was not associated with functional outcome in the fully adjusted model (final adjusted activities of daily living/instrumental activities of daily living score difference 0.11, 95% CI -0.07 to 0.30). Effect modification by ethnicity was not significant (P>0.3 for all models). Diabetes was associated with higher mortality and worse functional outcome but not stroke recurrence. Interventions are needed to decrease the adverse outcomes associated with diabetes, particularly in Mexican-American people.

Use of histamine H2 receptor antagonists and outcomes in patients with heart failure: a nationwide population-based cohort study.

BackgroundHistamine H2 receptor activation promotes cardiac fibrosis and apoptosis in mice. However, the potential effectiveness of histamine H2 receptor antagonists (H2RAs) in humans with heart failure is largely unknown. We examined the association between H2RA initiation and all-cause mortality among patients with heart failure.MethodsUsing Danish medical registries, we conducted a nationwide population-based active-comparator cohort study of new users of H2RAs and proton pump inhibitors (PPIs) after first-time hospitalization for heart failure during the period 1995−2014. Hazard ratios (HRs) for all-cause mortality and hospitalization due to worsening of heart failure, adjusting for age, sex, and time between heart failure diagnosis and initiation of PPI or H2RA therapy, index year, comorbidity, cardiac surgery, comedications, and socioeconomic status were computed based on Cox regression analysis.ResultsOur analysis included 42,902 PPI initiators (median age 78 years, 46% female) and 3,296 H2RA initiators (median age 76 years, 48% female). Mortality risk was lower among H2RA initiators than PPI initiators after 1 year (26% vs 31%) and 5 years (60% vs 66%). In multivariable analyses, the 1-year HR was 0.80 (95% CI, 0.74–0.86) and the 5-year HR was 0.85 (95% CI, 0.80–0.89). These findings were consistent after propensity score matching and for ischemic and nonischemic heart failure, as for sex and age groups. The rate of hospitalization due to worsening of heart failure was lower among H2RA initiators than PPI initiators.ConclusionIn patients with heart failure, H2RA initiation was associated with 15%–20% lower mortality than PPI initiation.

Major Adverse Renal and Cardiac Events After Coronary Angiography and Cardiac Surgery

Patients at high risk for having postprocedural complications may receive iodixanol, an iso-osmolar contrast, during coronary angiography to minimize the risk of renal toxicity. For those who also require cardiac surgery, the wait time between angiography and surgery may be a modifiable factor capable of mitigating poor surgical outcomes; however, there have been inconsistent reports regarding the optimal wait time. We sought to determine the effects of wait time between angiography and cardiac surgery, as well as contrast-induced acute kidney injury on the development of major adverse renal and cardiac events (MARCE). We merged datasets to identify adults who underwent coronary angiography with iodixanol and subsequent cardiac surgery. Of 965 patients, 126 (13.1%) had contrast-induced acute kidney injury; 133 (13.8%) had MARCE within 30 days and 253 (26.2%) within 1 year of surgery. After adjusting for contrast-induced acute kidney injury, age, and Thakar acute renal failure score, the effect of wait time lost significance for the full cohort, but remained for the subgroup of 654 who had coronary artery bypass graft surgery. Patients undergoing coronary artery bypass graft surgery within 1 day of coronary angiography had an approximate twofold increase in risk of MARCE (30-day hazard ratio 2.13, 95% confidence interval: 1.16 to 3.88, p= 0.014; 1-year hazard ratio 2.07, 95% confidence interval: 1.32 to 3.23, p= 0.002) compared with patients who waited 5 or more days. Patients who had contrast-induced acute kidney injury and had cardiac surgery within 1 day of angiography had an increased risk of MARCE.

A survival study of uterine cervical patients in the North East India

Uterine cervical cancer constitutes a major proportion of cancer in females of our population. The objective of this study was to conduct a clinical study of uterine cervical cancers including their survival from hospital-cancer registry data. Data of uterine cervical cancer patients diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a regional cancer center in North East (NE) India was recruited. The cases were analyzed for age group distribution, stage, and treatment types. Survival from the date of first diagnosis and hazard ratios (HRs) was estimated. Survival probability and HRs were calculated by Kaplan-Meier method and Cox-proportional regression analysis, respectively. Active follow-up was done for the survival analysis. One hundred and ninety-three patients (53.4%) were included for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in the age group of 45-64 years, 56.5% (109/193) were Stage II patients, radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5-year overall survival (OS) was 40.7%, median survival was 44 months, early staged and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002), respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval (CI) = 1.2 to 2.7). Describing the clinical characteristics and survival of uterine cervical cancer patients is important for planning and identifying the gaps for its control in the NE India.

Surgical treatment of active native mitral infective endocarditis: A meta-analysis of current evidence

BackgroundThe native mitral lesion of active infective endocarditis implies a poor prognosis and is associated with adverse short- or long-term results without surgical treatment. Both mitral valvuloplasty (MVP) and mitral valve replacement (MVR) have been performed in the treatment of active native mitral infective endocarditis (ANMIE). However, the outcomes of the two approaches remain unclear. The aim of this study was to systematically review the two procedures with mortality and survival as the primary endpoints. MethodsA systematic review of the literature was conducted to identify all relevant studies with comparative data on MVP versus MVR for the treatment of ANMIE. Information on baseline characteristics of patients, operation method, quality of literature, follow-up, and so forth was abstracted using standardized protocols. Pooled odds ratio (OR) or hazard ratio (HR) was calculated and possible publication bias was tested. ResultsNine comparative observational studies with a total of 633 patients (MVP = 265, MVR = 368) were identified for qualitative assessment, data extraction, and analysis. The summary OR for operative mortality, comparing repair with replacement, was 0.37 (95% CI 0.0.18–0.80; p = 0.0005). Summary 1- and 5-year HRs for event-free survival were 0.43 (95% CI 0.20–0.92; p = 0.03) and 0.44 (95% CI 0.25–0.77, p = 0.004), respectively (repair vs. replacement). Summary 1- and 5-year survival HRs were 0.51 (95% CI 0.24–1.08; p = 0.08) and 0.55 (95% CI 0.32–0.96; p = 0.004), respectively (repair vs. replacement). No heterogeneity was revealed between studies, and possible publication bias was insignificant. ConclusionsThis meta-analysis suggests that MVP may be associated with superior postoperative survival outcomes compared with MVR. MVP is desirable, if possible, as a durable alternative to replacement. However, we must consider the influence of different patient characteristics and surgeons' preferences on the choice of surgical approach, and additional powered clinical trials will be required to confirm these findings.

Machine Learning Improves Risk Stratification After Acute Coronary Syndrome

The accurate assessment of a patient’s risk of adverse events remains a mainstay of clinical care. Commonly used risk metrics have been based on logistic regression models that incorporate aspects of the medical history, presenting signs and symptoms, and lab values. More sophisticated methods, such as Artificial Neural Networks (ANN), form an attractive platform to build risk metrics because they can easily incorporate disparate pieces of data, yielding classifiers with improved performance. Using two cohorts consisting of patients admitted with a non-ST-segment elevation acute coronary syndrome, we constructed an ANN that identifies patients at high risk of cardiovascular death (CVD). The ANN was trained and tested using patient subsets derived from a cohort containing 4395 patients (Area Under the Curve (AUC) 0.743) and validated on an independent holdout set containing 861 patients (AUC 0.767). The ANN 1-year Hazard Ratio for CVD was 3.72 (95% confidence interval 1.04–14.3) after adjusting for the TIMI Risk Score, left ventricular ejection fraction, and B-type natriuretic peptide. A unique feature of our approach is that it captures small changes in the ST segment over time that cannot be detected by visual inspection. These findings highlight the important role that ANNs can play in risk stratification.

Elevated Admission Potassium Levels and 1-Year and 10-Year Mortality Among Patients With Heart Failure

BackgroundLimited, contradictory data exist regarding the effect of hyperkalemia on both short- and long-term all-cause mortality among hospitalized patients with heart failure (HF). MethodsWe analyzed 4,031 patients who were enrolled in the Heart Failure Survey in Israel. The study patients were grouped into 3 different potassium (K) categories. Multivariate analysis was used to determine the association of potassium levels as well as 1- and 10-year all-cause mortality. ResultsA total of 3,349 patients (83%) had K < 5mEq/L, whereas 461 patients (11%) had serum K ≥ 5mEq/L but≤ 5.5mEq/L and 221 patients (6%) had K > 5.5mEq/L. Survival analysis showed that 1-year mortality rates were significantly higher among patients with K > 5.5mEq/L (40%) and those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L (34%) compared to those with K < 5mEq/L (27%); (all log rank P < 0.01). Similarly, 10-year mortality rates among those with K > 5.5mEq/L were 92%, whereas among those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L rates were 88%, and in those with K < 5mEq/L rates were 82%; (all log rank P < 0.001). Consistently, multivariate analysis showed that compared to patients with K < 5mEq/L, patients with K > 5.5mEq/L had an independently 51% and 31% higher mortality risk at 1 year and 10 years, respectively (1-year hazard ratio = 1.51, 95% CI: 1.04-2.2; 10-years hazard ratio = 1.31, 95% CI: 1.035-1.66), whereas patients with serum K ≥ 5mEq/L but ≤ 5.5mEq/L had comparable adjusted mortality risk to patients with K < 5mEq/L at 1 and 10 years. ConclusionsAmong hospitalized patients with HF, admission K > 5.5mEq/L was independently associated with increased short- and long-term mortality, whereas serum K ≥ 5mEq/L but ≤ 5.5mEq/L was not independently associated with worse outcomes.

Comparative Effectiveness of Oral Antiplatelet Agents in Patients with Acute Coronary Syndrome.

In randomized controlled trials, prasugrel and ticagrelor reduced cardiovascular complications in patients with acute coronary syndrome (ACS) compared with clopidogrel. However, limited head-to-head comparisons have been conducted across the three antiplatelet agents using real-world data. The aim of this study was to compare clinical outcomes of three strategies during a 1-year period after percutaneous coronary intervention (PCI). Rates of all-cause and acute myocardial infarction (AMI) hospitalizations were compared retrospectively using an insurance claims database. Patients who filled a prescription for an oral antiplatelet agent between September 2011 and December 2013 for post ACS-PCI care were identified. Time to all-cause and AMI hospitalization for a 365-day postdischarge period was compared using Cox proportional hazard models controlling for potential confounders within a propensity score matched cohort. A matched cohort of 9504 clopidogrel, 7128 prasugrel, and 2376 ticagrelor patients was analyzed. The 1-year hazard ratio (HR) for the two newer agents versus clopidogrel was 0.84 (0.78-0.91). The HR for the newer agents versus clopidogrel of admission with AMI as the primary diagnosis was 0.78 (0.61-1.03), and for AMI as any diagnosis during a hospitalization was 0.88 (0.77-1.00). The HR of all-cause admission for ticagrelor versus prasugrel was 0.97 (0.84-1.13), and the HRs of AMI-related admission were not statistically significant between the two agents. Robustness checks across statistical methods to control for potential confounders did not influence the conclusion. This real-world study demonstrated that use of the newer agents following PCI was associated with a decrease in all-cause and AMI-related hospitalizations. However, no significant difference was found in the rate of admission between ticagrelor versus prasugrel. Due to concerns regarding statistical power, future studies should examine larger cohorts to obtain more precise estimates for AMI hospitalization for ticagrelor and prasugrel.

Radiotherapy versus radical prostatectomy for Gleason score 9-10 prostate adenocarcinoma: A multi-institutional comparative analysis of 1001 patients treated in the modern era.

7 Background: To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (CaP) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Methods: One-thousand-and-one patients with biopsy GS 9-10 CaP who received definitive treatment between 2000 and 2013 were included (347 treated with EBRT, 330 with EBRT+BT, and 324 with RP). Kaplan-Meier analysis and multivariate Cox regression compared 5- and 10-year rates of distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Prostate cancer-mortality (PCSM) rates were compared with a competing risk analysis. Results: The median followup periods were 4.8, 6.4, and 5.1 years among patients receiving EBRT, EBRT + BT, and RP. The median doses among EBRT and EBRT+BT patients were equivalent to 78 Gy and 90 Gy in 2 Gy fractions. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 18 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT, primarily in the salvage setting. Five- and 10-year DMFS rates were significantly higher with EBRT+BT (91.6% and 81.3%) than with EBRT (79.6% and 65.8%; p &lt; 0.0001) or RP (77.9% and 60.1%; p &lt; 0.0001). Five- and 10-year PCSM rates were significantly lower with EBRT+BT (3.8% and 14.1%) than with EBRT (10.3% and 25.2%; 5- and 10-year hazard ratios of 0.38 and 0.47; p = 0.003) or RP (8.9% and 20.3%; 5- and 10-year hazard ratios of 0.39 and 0.55; p = 0.02). Overall 5- and 10-year OS rates were 85.7% and 64.7% and were similar between cohorts (p &gt; 0.1). Conclusions: Extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT arm. This is hypothesis generating as it suggests that improved local control via dose-escalation may have systemic control and survival implications even for patients with very high risk disease.

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

A Novel Prognostic Index for Ocular Adnexal Lymphoma

Background: Ocular adnexal lymphoma (OAL) is a rare malignancy with a heterogeneous patient population. We sought to identify prognostic factors for OAL and to incorporate them into a novel prognostic index by using a large national database.Methods: We identified patients diagnosed with histologically confirmed OAL in 1973-2013 using all registries of the Surveillance, Epidemiology, and End Results database. Patients with regional or distant disease at diagnosis were excluded. Indolent histologies were defined as follicular, marginal zone, small lymphocytic not otherwise specified, and lymphoplasmacytic. We determined the association between OAL histology, orbital site, and overall survival (OS) using adjusted proportional hazards analysis and Kaplan-Meier estimates. Relative survival (RS) was calculated relative to a matched cohort of patients categorized by race, gender, and age using the SEER*Stat Program.Results: Among the 3,070 patients included, 941 (30.6%) had conjunctival tumors, 418 (13.7%) had lacrimal gland tumors, and 1711 (55.7%) had orbital-not otherwise specified tumors. Indolent histology was present in 2,073 (67.5%) patients. The 10-year OS and RS were 61% and 86%, respectively. In univariable and multivariable models, conjunctival site location (P<0.001) and indolent histology (P<0.001) were both associated with superior OS. Three primary OAL prognostic groups were identified: Group I (indolent histology, conjunctival location), Group II (indolent histology, non-conjunctival location or aggressive histology, conjunctival location), and Group III (aggressive histology, non-conjunctival location). The adjusted 10-year hazard ratios for OS were 1.4 (95% CI, 1.1-1.7, P<0.001) and 3.1 (95% CI, 2.5-4.0, P<0.001) for groups II and III, respectively, compared to group I. Groups I, II, and III had 10-year OS of 75%, 61%, and 37%, respectively, and 10-year RS of 96%, 89%, and 55%, respectively.Conclusions: Both conjunctival location and aggressive histology were independent predictors of survival. Our proposed prognostic index could have implications on OAL staging and management, though it must first be externally validated. DisclosuresNo relevant conflicts of interest to declare.

Incidence and survival of sebaceous carcinoma in the United States

Information on risk factors, epidemiology, and clinical characteristics of sebaceous carcinoma (SC) is limited. We sought to analyze trends in SC in the United States from 2000 through 2012. We used data from the 18 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from 2000 to 2012 to calculate the cause of death, relative frequencies/incidences, 5-/10-year Kaplan-Meier survival, hazard ratios, and incidence rates for SC. Each parameter was analyzed by age, location of occurrence (ocular/extraocular), race, sex, and SEER registry. Overall incidence was 0.32 (male) and 0.16 (female) per 100,000 person-years. Incidence significantly increased, primarily because of an increase among men. Incidence among whites was almost 3 times the rate among non-whites. Male sex (P<.0001), black race (P=.01), and extraocular anatomic location (P<.0001) were associated with significantly higher all-cause mortality. However, overall case-specific mortality for SC decreased significantly. Underregistration of patients in SEER registries, lack of verification of individual diagnoses, and low levels of staging data because of low stage-classification rate are limitations. The overall incidence of SC is increasing significantly. Male sex, black race, and extraocular occurrences are associated with significantly greater mortality.

Trastuzumab-Related Cardiotoxic Effects in Taiwanese Women: A Nationwide Cohort Study.

Trastuzumab is an essential medicine per the World Health Organization Model List, but its cardiac safety information in Asian women is limited. To estimate the rate and the risk of heart failure (HF) and/or cardiomyopathy (CM) in Asian women undergoing trastuzumab treatment. This cohort study used the Taiwanese National Health Insurance Research Database (NHIRD), a nationwide claim database covering more than 99% of the entire Taiwanese population, to identify 23 006 women with incident breast cancer (BC) who received chemotherapy from 2006 to 2009. We grouped women per their initial treatment regimens and found 1066 new trastuzumab users. We matched trastuzumab users with nonusers by year of BC diagnosis and propensity score (PS) with the caliper widths at 0.25 standard deviation of PS (up to 4 nonusers per trastuzumab user). The study lasted from January 2006 to December 2013 with a median follow-up of 5.29 years and a landmark design to avoid immortal time bias. Trastuzumab. To estimate HF and/or CM rates and time to HF and/or CM, we employed a cause-specific hazard model. Trastuzumab exposure was a time-dependent variable, while cumulative courses of chemotherapy agents with known cardiotoxic effects (including anthracyclines, taxanes, and cyclophosphamide) were defined as time-dependent covariates in the analysis model. We also performed 6 sensitivity analyses. In this cohort of 23 006 women (mean age, 50.99 years), the crude incidence of HF and/or CM was 4.03% in trastuzumab users and 2.88% in nonusers. The median time to HF and/or CM was 456 days in trastuzumab users and 966 days in nonusers. The 1-year cumulative hazard ratio was 1.86 (95% CI, 1.08-3.19). The sensitivity analyses yielded similar results. Compared with the published results, the trastuzumab-related HF and/or CM rate was 5-fold lower in Taiwanese women with breast cancer. Nonetheless, our cohort had a similar trastuzumab-related HF and/or CM risk. Our study provides critical cardiac safety information of trastuzumab for Asian women with BC under current treatment guidelines and label information.