Changes in Cognitive Function over 3 Years after First-Ever Stroke and Predictors of Cognitive Impairment and Long-Term Cognitive Stability: The Erlangen Stroke Project

Background and Purpose: Cognitive impairment (CI) is frequent after stroke, but data from population-based stroke cohorts on the natural course of CI are limited. The purpose of this study was to determine changes in cognitive status over 3 years after stroke. Methods: Data were collected from the Erlangen Stroke Project, an ongoing population-based stroke registry. The Mini-Mental State Examination (MMSE) for assessing global cognitive function was used; CI was defined as an MMSE score ! 24. Results: From February 1998 to January 2006, 630 patients with first-ever stroke were included. Prevalence rates of CI at 3 months, 1 and 3 years were 15, 13, and 12%. In multivariable analysis, stroke severity, i.e. Barthel index (p ! 0.001), age (OR = 1.03; 95% CI = 1.00–1.05) and diabetes mellitus (OR = 2.03; 95% CI = 1.13–3.67) were associated with CI at 3 months. Recovery rate from CI at 3 months after stroke was found to be 31% over the following 3 years. Intact cognitive function rate was 71% over 3 years and inversely associated with age (OR = 0.96; 95% CI = 0.96–0.94) and stroke severity (p ! 0.001). Conclusion: CI is frequent among stroke survivors and associated with age, stroke severity, and diabetes mellitus, but recovery occurs in approximately one third of the patients over the course of 3 years. Factors affecting intact cognitive function over time are increasing age and stroke severity

The Siblings With Ischemic Stroke Study (SWISS) Protocol

BACKGROUND: Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. METHODS: Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. DISCUSSION: Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios

Determining value in health technology assessment: Stay the course or tack away?

The economic evaluation of new health technologies to assess whether the value of the expected health benefits warrants the proposed additional costs has become an essential step in making novel interventions available to patients. This assessment of value is problematic because there exists no natural means to measure it. One approach is to assume that society wishes to maximize aggregate health, measured in terms of quality-adjusted life-years (QALYs). Commonly, a single 'cost-effectiveness' threshold is used to gauge whether the intervention is sufficiently efficient in doing so. This approach has come under fire for failing to account for societal values that favor treating more severe illness and ensuring equal access to resources, regardless of pre-existing conditions or capacity to benefit. Alternatives involving expansion of the measure of benefit or adjusting the threshold have been proposed and some have advocated tacking away from the cost per QALY entirely to implement therapeutic area-specific efficiency frontiers, multicriteria decision analysis or other approaches that keep the dimensions of benefit distinct and value them separately. In this paper, each of these alternative courses is considered, based on the experiences of the authors, with a view to clarifying their implications