Search

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired. ispartof: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY vol:163 issue:3 pages:1166-1175 ispartof: location:United States status: published

OBJECTIVES: The aim of this study was to investigate the association between systolic blood pressure (SBP) drop, worsening renal function (WRF), and prognosis in patients with acute heart failure (AHF).BACKGROUND: A large drop in SBP early after hospital admission for AHF might be associated with increased risk for WRF and prognosis. However, there is a paucity of data regarding the interaction between WRF and a drop in SBP on clinical outcomes.METHODS: A post hoc analysis among 6,544 patients with AHF enrolled in the RELAX-AHF-2 (Relaxin in Acute Heart Failure-2) trial was performed. Blood pressure was uniformly and repetitively measured. Peak SBP drop was defined as the difference between baseline SBP and lowest SBP documented during the first 48 hours. WRF was defined by an increase in serum creatinine of ≥0.3 mg/dL from baseline to day 5.RESULTS: Peak SBP drop was independently associated with a higher risk for WRF (HR: 1.11 per 10 mm Hg SBP drop; P < 0.001), 5-day worsening heart failure (HR: 1.12 per 10 mm Hg SBP drop; P = 0.006), and 180-day cardiovascular death (HR: 1.09 per 10 mm Hg SBP drop; P = 0.026) after adjustment for potential confounders including baseline SBP. There was no interaction between the prognostic value of early SBP drop according to the presence or absence of WRF.CONCLUSIONS: In patients hospitalized for AHF, a greater early drop in SBP was associated with a higher incidence of WRF, worsening heart failure, and an increased risk for 180-day cardiovascular death. However, the association between SBP drop and prognosis was not influenced by WRF. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778).

Background: The selective adenosine A1 receptor antagonist rolofylline showed a neutral overall result on clinical outcomes in the PROTECT trial. However, we hypothesized that response to rolofylline treatment could be influenced by underlying clinical risk.Methods: We performed a post-hoc analysis of the PROTECT trial -a large, double-blind, randomized, placebo-controlled trial that enrolled 2033 patients. Baseline risk of 180-day all-cause mortality was estimated using a previously published 8-item model. Evaluation of efficacy of rolofylline across subpopulations defined based on estimated risk of mortality was performed using subpopulation treatment effect pattern plot (STEPP) analysis. Findings were validated in an independent cohort of acute heart failure patients.Results: Median estimated risk of mortality was 13.0%, IQR [8.0%-23.0%] and was comparable between the rolofylline and placebo arms. In low to intermediate risk subgroups of patients, rolofylline was associated with a higher rate of 180-day all-cause mortality (11.9% in the rolofylline versus 8.4% in the placebo arms, p = 0.050). In the high risk subgroup of patients, particularly those with estimated risk of mortality between 20% and 30%, 180-day all-cause mortality rate was markedly lower in the rolofylline arm(18.4% in the rolofylline versus 34.0% in the placebo arms, p = 0.003). The trend towards potential harm with rolofylline treatment in the low to intermediate risk subpopulations and significant benefit in high risk patients was also observed in the validation cohort.Conclusion: Our findings suggest that selective adenosine A1 receptor antagonism could be harmful in low risk acute heart failure patients, while it might significantly benefit higher risk patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Objectives: Early estimates of the commercial headroom available to a new medical device can assist producers of health technology in making appropriate product investment decisions. The purpose of this study was to illustrate how this quantity can be captured probabilistically by combining probability elicitation with early health economic modeling. The technology considered was a novel point-of-care testing device in heart failure disease management. Methods: First, we developed a continuous-time Markov model to represent the patients' disease progression under the current care setting. Next, we identified the model parameters that are likely to change after the introduction of the new device and interviewed three cardiologists to capture the probability distributions of these parameters. Finally, we obtained the probability distribution of the commercial headroom available per measurement by propagating the uncertainty in the model inputs to uncertainty in modeled outcomes. Results: For a willingness-to-pay value of (sic)10,000 per life-year, the median headroom available per measurement was (sic)1.64 (interquartile range (sic)0.05-(sic)3.16) when the measurement frequency was assumed to be daily. In the subsequently conducted sensitivity analysis, this median value increased to a maximum of (sic)57.70 for different combinations of the willingness-to-pay threshold and the measurement frequency. Conclusions: Probability elicitation can successfully be combined with early health economic modeling to obtain the probability distribution of the headroom available to a new medical technology. Subsequently feeding this distribution into a product investment evaluation method enables stakeholders to make more informed decisions regarding to which markets a currently available product prototype should be targeted.

Objective: To enable multicriteria benefit risk (BR) assessment of any number of alternative treatments using all available evidence from a network of clinical trials.Study Design and Setting: We design a general method for multicriteria decision aiding with criteria measurements from Mixed Treatment Comparison (MTC) analyses. To evaluate the method, we apply it to BR assessment of four second-generation antidepressants and placebo in the setting of a published peer-reviewed systematic review.Results: The analysis without preference information shows that placebo is supported by a wide range of possible preferences. Preference information provided by a clinical expert showed that although treatment with antidepressants is warranted for severely depressed patients, for mildly depressed patients placebo is likely to be the best option. It is difficult to choose between the four antidepressants, and the results of the model indicate a high degree of uncertainty.Conclusions: The designed method enables quantitative BR analysis of alternative treatments using all available evidence from a network of clinical trials. The preference-free analysis can be useful in presenting the results of an MTC considering multiple outcomes. (C) 2012 Elsevier Inc. All rights reserved.

Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. Biomarker profiles might identify subsets of patients that respond. We studied the effect of rolofylline on 180 day mortality across 24 clinical

Objectives: Use of proton instead of photon radiation therapy for head and neck cancer reduces the primary tumor and damage to adjacent organs risk, which results in fewer complications. These complications decrease quality of life (QOL). To support better decision making concerning which patients benefit most from proton therapy, a patient-level simulation model is developed and applied to compare outcomes. Methods: Model estimates, such as patient and tumor characteristics follow-up time, and survival, were based on patient-level data containing patients treated with radiation therapy as first line therapy for head and neck tumor in The Netherlands between 1980-2010 at the UMC Groningen (n= 277) and VU Amsterdam (n= 736). In silico radiation treatment planning schemes for both proton and photon therapy allowed to compare a priori expected health benefits and cost consequences for both therapy modes to support a patient tailored choice. Results: Patients experienced their first event at a median time of 30 (0-270, SD 34) months' time. Loco-regional recurrency in 29%, distant metastasis in 4.2%, both combined in 1% and dead in 13.3% of patients. Cost per year for photon was estimated € 15000, proton € 30000, disease free state € 190, local regional recurrence € 28000, metastases € 35000 and both € 35000. For the complication sticky saliva costs per year of an average patient were € 31, xerostomia € 194, dysphagia € 57, tube feeding € 4262, and hypothyroidism € 117. Proton radiation therapy leads to less complications and improved QOL. Conclusions: Given the high costs of proton therapy, this was found not to be cost-effective compared to best photon therapy in an average patient with head and neck cancer. However, the outcomes vary substantially between patients. Depending on patient and tumor characteristics for selected patients with high complication risks, proton therapy can be a better option.

Objectives: Recent ISPOR Good practice guidelines as well as literature encourage to use a single distribution rather than the latent failure approach to model time to event for patient level simulation models with multiple competing outcomes. Aim was to apply the preferred method of a single distribution on time to event in combination with a multinomial distribution on type of event for parameterizing the primary tumor component of a patient level head and neck cancer model. Methods: Data on patients treated with radiation therapy as first line therapy for head and neck tumor at two university hospitals in The Netherlands between 25-02-1980- 13-12-2010 was used (nUMCG= 277 & nVUMC= 736). Several distributions were tested for model fit, using QQ-plots, AIC, and simulated versus actual data plots to judge best fit. Covariates tested for inclusion were age, gender, tumor location dummies, nstage and tstage. The final model was applied in the patient simulation model. Multinomial regression with the same covariates and time of event added as a covariate was applied on type of event, distinguishing death, loco regional recurrence and metastasis as events. All analyses were performed in R. Results: The LogNormal distribution showed best fit. The final model had the following coefficients for the location parameter (se in brackets): Intercept, 8.2 (0.38), Age -0.026 (0.0053), Tstage -0.38 ( 0.062), Nstage -0.21 (0.076), Locd1 -0.91 (0.22) , Locd2 -0.28 (0.15), Locd3 -0.72 (0.22). Locd refers to location dummies. The estimated value for Log(sd) was -0.44 (0.038). The multinomial model had age, tstage and time of event as significant covariates Conclusions: A disadvantage of this method is that a single distribution has to be fit to a time of event which is the result of different interacting stochastic processes. The resulting distributions showed acceptable fit and could be implemented straightforwardly in the patient level simulation model.