The nonparametric model was preferred for its simplicity while performing similarly to the other models. Being independent of the value set that is used, it can be applied to transform any EQ-5D-3L value set into EQ-5D-5L index values. Strengths of this approach include compatibility with three-level value sets. A limitation of any crosswalk is that the range of index values is restricted to the range of the EQ-5D-3L value sets.

BackgroundThere are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments – EDSS and MSFC – meet methodological standards and the value they have in clinical trials.MethodsWe conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.ResultsFor evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).ConclusionsRecognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.

BackgroundSince the introduction of the five-level version of the EQ-5D (5L), many studies have comparatively investigated the measurement properties of the original three-level version (3L) with the 5L version.ObjectiveThe aim of this study was to consolidate the available evidence on the performance of both instruments.MethodsA systematic literature search of studies in the English and German languages was conducted (2007–January 2018) using the PubMed, EMBASE, and PsycINFO (EBSCO) databases, as well as the EuroQol Research Foundation website. Data were extracted and assessed on missing values, distributional properties, informativity indices (Shannon’s H′ and J′), inconsistencies, responsiveness, and test–retest reliability.ResultsTwenty-four studies were included in the review. Missing values and floor effects (percentage reporting the worst health state) were found to be negligible for both 3L and 5L (< 5%). From 18 studies, inconsistencies ranged from 0 to 10.6%, although they were generally well below 5%, with 9 studies reporting the most inconsistencies for Usual Activities (mean percentage 4.1%). Shannon’s indices were always higher for 5L than for 3L, and all but three studies reported lower ceiling effects (‘11111’) for 5L than for 3L. There is mixed and insufficient evidence on responsiveness and test–retest reliability, although results on index values showed better performance for 5L on test–retest reliability.ConclusionOverall, studies showed similar or better measurement properties of the 5L compared with the 3L, and evidence indicated moderately better distributional parameters and substantial improvement in informativity for the 5L compared with the 3L. Insufficient evidence on responsiveness and test–retest reliability implies further research is needed.Electronic supplementary materialThe online version of this article (10.1007/s40273-018-0642-5) contains supplementary material, which is available to authorized users.

strategy reduces the risk of overestimating adherence. For prescriptions extending beyond the end of the analysis period, days' supply is truncated at the end of the period. Patients in each study sample are stratified into 5 categories based on their adherence score: 1-19%, 20-39%, 40-59%, 60-79%, or 80-100 %. Results: High level of medication adherence was associated with lower hospitalization and exacerbation rates. ConClusions: Increased drug utilization can provide a net economic return when it is driven by improved adherence.

BackgroundCachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia.FindingsWe screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM) kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4%) in controls (p < 0,05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.).ConclusionWhile these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

Cross-sectionally and longitudinally, 5L was associated with an improved ability to detect health changes over time, reduced ceiling effects, and improved discriminatory power. Overall, these findings were in line with previous study outcomes, although differing in magnitude. Since the sample size is moderate and generalizability of the reported results is unclear, further comparisons in other patient populations will be informative and should be encouraged.

Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder. Oral anticoagulation (OAC) is recommended by guidelines in the presence of a moderate to high risk of stroke. Based on an analysis of claims-based data, the aim of this contribution is to quantify the stroke-risk dependent OAC utilisation profile of German AF patients as well as the possible causes and the associated clinical outcomes of OAC under-use. Our data set was derived from two large mandatory German medical insurance funds. Risk stratification of patients was based on the CHADS2-score and the CHA2DS2-VASc-score. Two different scenarios were constructed to deal with factors potentially disfavouring OAC use. Causes of OAC under-use and its clinical consequences were analysed using multivariate analysis. Observation year was 2008. A total of 183,448 AF patients met the inclusion criteria. This represents an AF prevalence of 2.21%. The average CHADS2-score was 2.8 (CHA2DS2-VASc-score: 4.3). On between 40.5 and 48.7% of the observed patient-days, there was no antithrombotic protection by OAC, other anticoagulants or aspirin. Older female patients with a high number of comorbidities had a higher risk of OAC under-use. Patients who had already experienced a thromboembolic event had a lower risk of OAC under-use. In the observation year, 3,367 patients experienced a stroke (incidence rate 1.8%). In our multi-level Poisson random effects estimate, OAC use decreases the stroke rate by almost 80% (IRR 0.236). In conclusion, OAC under-use is widespread in the German market. It is associated with severe clinical consequences.

Although iso-BMI was associated with dental caries prevalence and severity, the association between caries increment and iso-BMI did not reach a statistical significance. Overweight/obese children however acquired more additional carious lesions during the follow-up period than children with low-normal weight.