Abstract Background Economic evaluations often measure an intervention effect with mean overall survival (OS). Emerging types of cancer treatments offer the possibility of being “cured” in that ...patients can become long-term survivors whose risk of death is the same as that of a disease-free person. Describing cured and noncured patients with one shared mean value may provide a biased assessment of a therapy with a cured proportion. Objective The purpose of this article is to explain how to incorporate the heterogeneity from cured patients into health economic evaluation. Methods We analyzed clinical trial data from patients with advanced melanoma treated with ipilimumab (Ipi; n = 137) versus glycoprotein 100 (gp100; n = 136) with statistical methodology for mixture cure models. Both cured and noncured patients were subject to background mortality not related to cancer. Results When ignoring cured proportions, we found that patients treated with Ipi had an estimated mean OS that was 8 months longer than that of patients treated with gp100. Cure model analysis showed that the cured proportion drove this difference, with 21% cured on Ipi versus 6% cured on gp100. The mean OS among the noncured cohort patients was 10 and 9 months with Ipi and gp100, respectively. The mean OS among cured patients was 26 years on both arms. When ignoring cured proportions, we found that the incremental cost-effectiveness ratio (ICER) when comparing Ipi with gp100 was $324,000/quality-adjusted life-year (QALY) (95% confidence interval $254,000–$600,000). With a mixture cure model, the ICER when comparing Ipi with gp100 was $113,000/QALY (95% confidence interval $101,000–$154,000). Conclusions This analysis supports using cure modeling in health economic evaluation in advanced melanoma. When a proportion of patients may be long-term survivors, using cure models may reduce bias in OS estimates and provide more accurate estimates of health economic measures, including QALYs and ICERs.
Summary Background Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the ...intention of improving the health benefits of screening. Methods All people eligible for screening (men and women aged 60–74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July–August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. Findings As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163 525) and 2 (n=150 417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio OR 1·07, 95% CI 1·04–1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04–1·20, p=0·003) than in the least deprived (1·00, 0·94–1·06, p=0·98). Overall uptake was also increased (1·07, 1·03–1·11, p=0·001). Interpretation Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging. Funding National Institute for Health Research.
Abstract Objective Overall survival is a commonly reported end point in clinical trial publications and a key determinant of therapies’ cost-effectiveness. Patients’ survival times have skewed ...distributions. Outcomes are typically presented in clinical trials as the difference in median survival times; we compare median survival gain with the measure required for economic evaluation, the mean difference. Study Design We summarize the relationships between median and mean survival in 4 parametric survival distributions and the relationship of the differences in these measures between trial arms and parameterized treatment effects. Parametric estimates of mean survival were compared with median survival in a case study of a recent trial in metastatic melanoma. Results In a trial of alternative therapies in unresectable metastatic melanoma, median overall survival with ipilimumab alone was 10.1 months versus 6.4 months with gp100-alone (hazard ratio 0.66; P = 0.003). A log-normal parametric survivor function fitted the gp100 Kaplan-Meier function and a time ratio of 1.90 applied only after 90 days gave a suitable fit to the Kaplan-Meier function for ipilimumab, with mean survival difference of 7 months, compared with an estimate of 5.7 months employing a Weibull distribution, and with a 3.7-months median difference. Conclusion Parametric assessment of mean survival gain in clinical trials may indicate potential benefits to patients that observed medians may greatly underestimate.
Abstract Objective Viral hepatitis C (HCV) affects 170 million patients worldwide and 2 million patients in Japan. The objective of the current study was to examine the burden of HCV in Japan from a ...patient's perspective. Methods Using data from the 2008 and 2009 Japan National Health and Wellness Surveys, patients who reported an HCV diagnosis (n = 306) were compared with a propensity-score–matched control group (n = 306) on measures of quality of life (using the Medical Outcomes Study 12-Item Short Form Survey Instrument version 2), work productivity (using the Work Productivity and Activity Impairment questionnaire), and health-care resource use. All analyses applied sampling weights to project to the population. Results Prior to matching, patients with HCV had higher rates of hepatocellular carcinoma (4.88% vs. 0.02%) and cirrhosis (12.20% vs. 0.11%) than did subjects without HCV. The propensity-matching process eliminated differences between the two groups on demographics and patient characteristics. The postmatching analysis found significantly lower levels of quality of life for patients with HCV as measured by bodily pain (72.07 vs. 76.28), general health (44.64 vs. 48.61), and mental health (66.50 vs. 70.32) (all P s < 0.05). Furthermore, compared with the matched group, the HCV group had significantly higher workplace absenteeism (8.59% vs. 4.12%), overall work impairment (26.08% vs. 17.32%), and health-care provider visits in the past 6 months (14.80 vs. 9.74). Conclusions The results of this study suggest that HCV can be a substantial burden on patients in terms of quality of life in both physical and mental health measures. In addition, HCV can be a significant cost driver in terms of health-care use and lost productivity.
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•A simple, biohybrid patch made of polymer (PECUU) and ECM, without cellular components, was able to induce positive remodeling features when applied over chronic infarcts with ...severely dilated hearts and high cardiac function impairment in rats.•The remodeling benefit was particularly notable in a subgroup of the sickest rats with very low initial ejection fraction in which the echocardiographic endpoints were found to improve after treatment.•This technological approach may hold promise for future translation to patients in a chronic scenario.
A biohybrid patch without cellular components was implanted over large infarcted areas in severely dilated hearts. Nonpatched animals were assigned to control or losartan therapy. Patch-implanted animals responded with better morphological and functional echocardiographic endpoints, which were more evident in a subgroup of animals with very low pre-treatment ejection fraction (<35%). Patched animals also had smaller infarcts than both nonpatched groups. This simple approach could hold promise for clinical translation and be applied using minimally invasive procedures over the epicardium in a large set of patients to induce better ventricular remodeling, especially among those who are especially frail.
An obituary for Galen S. Wagner, the editor-in-chief of the Journal of Electrocardiology who died on Jul 13, 2016, is presented. Being active as the director of the Cardiac Care Unit of the Duke ...University Medical Center from 1968 to 1981, Wagner was instrumental in the development of the world renowned Duke Cardiovascular Databank. He also helped establish the International Research Interdisciplinary School that offers outcome-research training programs in countries throughout the world that has been ongoing for the past eleven years.
Guidelines recommend that patients with suggestive symptoms of myocardial ischemia and ST-segment elevation (STE) in ≥2 adjacent electrocardiographic leads should receive immediate reperfusion ...therapy. Novel strategies aimed to reduce door-to-balloon time, such as prehospital wireless electrocardiographic transmission, may be dependent on the interpretation accuracy of the electrocardiogram (ECG) readers. We assessed the ability of experienced electrocardiographers to differentiate among STE, acute STE myocardial infarction (STEMI), and nonischemic STE (NISTE). A total of 116 consecutive ECGs showing STE were studied. Fifteen experienced cardiologists were asked to decide, based on the ECG and assuming that the patient had compatible symptoms, whether they would send each patient for primary percutaneous coronary intervention (PPCI). If NISTE was chosen, the reader selected 1 or more 12 possible options to explain the choice. Of 116 patients, only 8 had STEMI. The percentage of ECGs for which PPCI was recommended for the patient by the individual readers varied widely (7.8% to 33%). There was no significant difference between the North American and Other Countries readers (p = 0.13). The sensitivity and specificity of the individual readers ranged from 50% to 100% (average 75%) and 73% to 97% (average 85%), respectively. There were broad inconsistencies among the readers in the chosen reasons used to classify NISTE. In conclusion, we found wide variations among experienced electrocardiographers in reading ECGs with STE and differentiating STEMI with need for PPCI from NISTE. There is a need to revise our current electrocardiographic criteria for differentiating STEMI from NISTE.
Infections involving thoracic aortic grafts are difficult to treat and have devastating consequences. The traditional approaches to surgical management include aggressive debridement with graft ...explantation and replacement. Despite treatment, the reported morbidity and mortality rates are high. The purpose of this study was to present our experience with an innovative approach to aortic graft salvage in the setting of sternal wound infection using antibiotic impregnated polymethylmethacrylate beads followed by definitive wound closure with flap coverage. A retrospective review identified patients with surgical wounds after aortic graft or cardiac valve placement over a 7-year period at a single institution. Patients were treated using an algorithm consisting of repeated surgical debridement and placement of antibiotic beads followed by flap coverage after suppression of the infection. A total of 20 patients were treated for surgical wounds, including 19 sternal and one thoracotomy wound. Culture positive surgical site infections were documented in 16 patients. One patient required a bead exchange before definitive closure. There were no in-hospital mortalities. All but two patients achieved successful infection suppression and wound closure with flap coverage. The use of antibiotic beads with serial debridement and flap closure may offer a valid option for aortic graft salvage in the setting of infected sternal wounds in the appropriate patient population. The proposed algorithm showed that patients may be successfully treated, and their infection suppressed without the need for graft removal. Mortality rates were lower from those previously reported in the literature.
Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case ...verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa.
In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region.
We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%).
On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy.
The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.
Abstract The International Research Interdisciplinary School (IRIS) provides an interdisciplinary international environment for training skills required for preparing research study protocols, ...scientific manuscript and international collaboration. It is a common initiative of the Journal of Electrocardiology, Anatolian Journal of Cardiology, Monitor of Medicine of the Slovak Medical Society, Balkan Medical Journal, Central Asian Medical Journal, and Journal of Kyrgyz State Medical Academy, Cardiovascular Systems. In the period from 2006 to 2016, nineteen IRIS courses were organized in twelve countries on three continents (Austria, Brazil, Croatia, Kazakhstan, Kyrgyzstan, Macedonia, Poland, Romania, Russia, Slovakia, Spain, Turkey). Total number of participants is 315, from 33 countries (Albania, Austria, Bosnia and Herzegovina, Brazil, China, Colombia, Croatia, Czech Republic, Denmark, Egypt, Estonia, Georgia, Greece, Hong Kong, Hungary, Kazakhstan, Kosovo, Kyrgyzstan, Lithuania, Macedonia, The Netherlands, Poland, Portugal, Romania, Russia, Serbia and Montenegro, Slovakia, Spain, Sweden, Turkey, Ukraine, USA, Venezuela). The evaluation of the scientific performance of trainees for the period 2007–2013 showed that the IRIS training was associated with identifiable increase in scientific publication activity. The Journals benefited from the increased quality of submitted manuscripts and an increased pool of peer-reviewers.
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