External quality assessment of urinary methylmalonic acid quantification - results of a pilot study

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Contemporary outcome measures in acute stroke research: choice of primary outcome measure

BACKGROUND AND PURPOSE: The diversity of available outcome measures for acute stroke trials is challenging and implies that the scales may be imperfect. To assist researchers planning trials and to aid interpretation, this article reviews and makes recommendations on the available choices of scales. The aim is to identify an approach that will be universally accepted and that should be included in most acute trials, without seeking to restrict options for special circumstances. METHODS: The article considers outcome measures that have been widely used or are currently advised. It examines desirable properties for outcome measures such as validity, relevance, responsiveness, statistical properties, availability of training, cultural and language issues, resistance to comorbidity, as well as potential weaknesses. Tracking and agreement among outcomes are covered. RESULTS: Typical ranges of scores for the common scales are described, along with their statistical properties, which in turn influence optimal analytic techniques. The timing of recovery on scores and usual practice in trial design are considered. CONCLUSIONS: The preferred outcome measure for acute trials is the modified Rankin Scale, assessed at 3 months after stroke onset or later. The interview should be conducted by a certified rater and should involve both the patient and any relevant caregiver. Incremental benefits at any level of the modified Rankin Scale may be acceptable. The modified Rankin Scale is imperfect but should be retained in its present form for comparability with existing treatment comparisons. No second measure should be required, but correlations with supporting scales may be used to confirm consistency in direction of effects on other measures

The interaction between policy and education using stroke as an example

This paper discusses the interaction between healthcare policy at the European, UK and Scottish levels and the funding of education that underpins specific health policy priorities. Stroke is used throughout to illustrate the relationship between a designated European and UK health priority and the translation of that priority into clinical delivery. The necessity to build a responsive and sustainable culture to address the healthcare education that underpins changing healthcare policies is emphasized

The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice : systematic review and economic evaluation

Funding The National Institute for Health Research Health Technology Assessment programme.Peer reviewedPublisher PD

Cross-Calibration of Stroke Disability Measures: Bayesian Analysis of Longitudinal Ordinal Categorical Data Using Negative Dependence

It is common to assess disability of stroke patients using standardized scales, such as the Rankin Stroke Outcome Scale (RS) and the Barthel Index (BI). The Rankin Scale, which was designed for applications to stroke, is based on assessing directly the global conditions of a patient. The Barthel Index, which was designed for general applications, is based on a series of questions about the patient’s ability to carry out 10 basis activities of daily living. As both scales are commonly used, but few studies use both, translating between scales is important in gaining an overall understanding of the efficacy of alternative treatments, and in developing prognostic models that combine several data sets. The objective of our analysis is to provide a tool for translating between BI and RS. Specifically, we estimate the conditional probability distributions of each given the other. Subjects consisted of 459 individuals who sustained a stroke and who were recruited for the Kansas City Stroke Study from 1995 to 1998. Patients were assessed with BI and RS measures 1, 3 and 6 months after stroke. In addition, we included data from the Framingham study, in the form of cross-classifying patients by RS and coarsely aggregated BI. Our statistical estimation approach is motivated by several goals: (a) overcoming the difficulty presented by the fact that our two sources report data at different resolutions; (b) smoothing the empirical counts to provide estimates of probabilities in regions of the table that are sparsely population; (c) avoiding estimates that would conflict with medical knowledge about the relationship between the two measures and (d) estimating the relationship between RS and BI at three months after the stroke, while borrowing strength from measurements made at one and six months. We address these issues via a Bayesian analysis combining data augmentation and constrained semiparametric inference. Our results provide the basis for (a) comparing and integrating the results of clinical trials using different measures, and (b) integrating clinical trials results into comprehensive decision model for the assessment of long term implications and cost-effectiveness of stroke prevention and acute treatment interventions. In addition, our results indicate that the degree of agreement between the two measures is less strong than commonly reported, and emphasize the importance of trial designs that include multiple assessments of outcome

Projection of young-old and old-old with functional disability: Does accounting for the changing educational composition of the elderly population make a difference?

10.1371/journal.pone.0126471PLoS ONE105e012647

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Comparing health workforce forecasting approaches for healthcare planning: The case for ophthalmologists

Health workforce planning is essential in the provision of quality healthcare. Several approaches to planning are customarily used and advocated, each with unique underlying assumptions. Thus, a thorough understanding of each assumption is required in order to make an informed decision on the choice of forecasting approach to be used. For illustration, we compare results for eye care requirements in Singapore using three established workforce forecasting approaches – workforce-to-population-ratio, needs based approach, utilization based approach – and a proposed robust integrated approach to discuss the appropriateness of each approach under various scenarios. Four simulation models using the systems modeling methodology of system dynamics were developed for use in each approach. These models were initialized and simulated using the example of eye care workforce planning in Singapore, to project the number of ophthalmologists required up to the year 2040 under the four different approaches. We found that each approach projects a different number of ophthalmologists required over time. The needs based approach tends to project the largest number of required ophthalmologists, followed by integrated, utilization based and workforce-to-population ratio approaches in descending order. The four different approaches vary widely in their forecasted workforce requirements and reinforce the need to be discerning of the fundamental differences of each approach in order to choose the most appropriate one. Further, health workforce planning should also be approached in a comprehensive and integrated manner that accounts for developments in demographic and healthcare systems

The influence of genotype on warfarin maintenance dose predictions produced using a Bayesian dose individualization tool

Background A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In the following study, we aimed to (1) determine if the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from two different clinical settings, (2) explore the influence of CYP2C9 and VKORC1 genotype on the predictive performance of the Bayesian dosing tool, and (3) determine if the prior population used to develop the kinetic-pharmacodynamic (KPD) model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions. Methods The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared to the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (e.g., EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic-pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates to published values. Results The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% CI]; 0.32 mg/day [0.14, 0.5]). The bias was only observed in patients requiring ≥7 mg/day. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, suggesting that the bias was not caused by different prior and posterior populations. Conclusions Maintenance doses for patients requiring ≥7 mg/day were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose–response relationship at higher warfarin dose