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BackgroundSurrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes.Methods and ResultsWe identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine, Lancet, and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high‐impact journals.ConclusionsAlthough cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high‐profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it.

Background: Noninferiority trials are increasingly being performed. However, little is known about their methodological quality. We sought to characterize noninferiority cardiovascular trials published in the highest-impact journals, features that may bias results toward noninferiority, features related to reporting of noninferiority trials, and the time trends. Methods: We identified cardiovascular noninferiority trials published in JAMA , Lancet , or New England Journal of Medicine from 1990 to 2016. Two independent reviewers extracted the data. Data elements included the noninferiority margin and the success of studies in achieving noninferiority. The proportion of trials showing major or minor features that may have affected the noninferiority inference was determined. Major factors included the lack of presenting the results in both intention-to-treat and per-protocol/as-treated cohorts, α>0.05, the new intervention not being compared with the best alternative, not justifying the noninferiority margin, and exclusion or loss of ≥10% of the cohort. Minor factors included suboptimal blinding, allocation concealment, and others. Results: From 2544 screened studies, we identified 111 noninferiority cardiovascular trials. Noninferiority margins varied widely: risk differences of 0.4% to 25%, hazard ratios of 1.05 to 2.85, odds ratios of 1.1 to 2.0, and relative risks of 1.1 to 1.8. Eighty-six trials claimed noninferiority, of which 20 showed superiority, whereas 23 (21.1%) did not show noninferiority, of which 8 also demonstrated inferiority. Only 7 (6.3%) trials were considered low risk for all the major and minor biasing factors. Among common major factors for bias, 41 (37%) did not confirm the findings in both intention-to-treat and per-protocol/as-treated cohorts and 4 (3.6%) reported discrepant results between intention-to-treat and per-protocol analyses. Forty-three (38.7%) did not justify the noninferiority margin. Overall, 27 (24.3%) underenrolled or had >10% exclusions. Sixty trials (54.0%) were open label. Allocation concealment was not maintained or unclear in 11 (9.9%). Publication of noninferiority trials increased over time ( P <0.001). Fifty-two (46.8%) were published after 2010 and had a lower risk of methodological or reporting limitations for major ( P =0.03) and minor factors ( P =0.002). Conclusions: Noninferiority trials in highest-impact journals commonly conclude noninferiority of the tested intervention, but vary markedly in the selected noninferiority margin, and frequently have limitations that may impact the inference related to noninferiority.

This  study  aims  to  determine  the  effect  of  financial  knowledge  and  financial  socialization  on the financial satisfaction of the individuals when unexpected life events happen and to examine the mediating role of the financial stressor and financial behavior between them. The data collected from 243 respondents who had experienced any unexpected hospitality in the state of Azad Jammu and Kashmir. Grab sampling method utilized for data collection. Confirmatory factor analysis (CFA) and Structural Equation Modeling (SEM) utilized for data analysis. Results of study reveal that: 1) financial knowledge and financial socialization have positive influence on financial satisfaction; 2) financial knowledge has positive effect on financial satisfaction with the mediating role of the financial stressor and financial behavior when an unexpected life event happens; and 3) financial socialization has positive effect on financial satisfaction with the mediating role of the financial stressor and financial behavior when an unexpected life event happened. This study provides clear insight toward the financial satisfaction of the individuals while confronting the unexpected life events. Practitioners and financial planners use this article for increasing the financial satisfaction of their customers. There is a plethora of researches conducted in different perspective except life events of individuals. This study utilized confirmatory factor analysis, which is necessary when research carried out from a different perspective.

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SCA in settings of ESRD on dialysis carries high mortality and frequent morbidity. Further research in therapeutic interventions that could prevent SCA in this vulnerable population is utmost needed.

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Background Cardiogenic shock (CS) is often associated with severe heart rhythm disturbances (SHRD). Percutaneous left ventricular assist devices (pLVAD) can actively unload the left ventricle (LV) using a micro-axial pump and resulting in a decreased end-diastolic pressure and wall tension. These parameters are suspected to induce and maintain rhythmological instability. Purpose In the current study, we firstly describe the termination of SHRD immediately (less than 5 minutes) after LV-unloading in CS patients with previous unsuccessful antiarrhythmic treatment. Methods The Dresden Impella Registry is an ongoing single center registry. Since 2014, a total of 97 patients were included. Each of whom had received a micro-axial heart pump in refractory CS supplying a circulatory support of 3.5 l/min. We investigated the subgroup of patients which initially exhibited SHRD like ventricular tachycardia or ventricular fibrillation, and showed an immediately stabilization of heart rhythm directly after insertion of pLVAD (HRS). This subgroup was compared with the other patients of the registry (NHRS). Therefore, clinical laboratory and hemodynamic parameters were measured and analyzed. Results In 19 patients of the registry a HRS was observed. Among these patients, a CPR before pLVAD was performed in 89.5% with a mean duration of 30.7min, whereby 52.6% sustained an in-hospital cardiac arrest and 36.9% an out-of-hospital cardiac arrest respectively. In the NHRS subgroup (n=78), a CPR was performed less frequently (39.7%; p<0.001) with shorter mean duration (19.5min; p=0.016) and a lower out-of-hospital ratio (12.8%; p=0.014). The comparison of hemodynamic parameters between the HRS and NHRS cohort showed no difference in mean arterial pressure, heart rate, left ventricular ejection fraction (LVEF), and serum lactate. The mortality showed no differences between the HRS and NHRS cohort at 30 days (68.4% vs. 58.1%; p=0.413) and 90 days (78.9% vs. 66.7%; p=0.306), despite a more frequent and longer CPR with a higher ratio of out-of-hospital cardiac arrests among the HRS patients. There was also no difference in mortality between patients, who received an in-hospital CPR. However, HRS patients with in-hospital CPR showed a significantly lower serum lactate and NA dosage compared to the NHRS cohort (Figure A & B). Furthermore, NA recovery, defined as 50% decrease as compared to the initial NA dosage, occurred more frequently in the HRS group (HRS 42.9% vs. NHRS 7.1%; p=0.049). The LVEF nearly double in the HRS subgroup after LV-unloading, whereas it did not change in the NHRS subgroup (relative LVEF increase: HRS 95% vs. NHRS 15%). Figure A & B Conclusion The termination of SHRD due to LV-unloading occurred in around 20% of CS patients in Dresden Impella Registry and was associated with a lower serum lactate and NA dosage as well as an improved LVEF among patients with in-hospital CPR. Acknowledgement/Funding None