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The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (=3 months), medium- (=1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV1, dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years). A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes.

OBJECTIVE: To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. DATA SOURCES: Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. METHODS OF STUDY SELECTION: We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. TABULATION, INTEGRATION, AND RESULTS: We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. CONCLUSION: Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding. (Obstet Gynecol 2010;116:160-7)

There are only few experimental studies that assess the hypothesis that placebo analgesia is mediated by endogenous opioids. One of these studies [Grevert P, Albert LH, Goldstein A: Partial antagonism of placebo analgesia by naloxone. Pain 1983;16:129-143] had a rather complicated design and data presentation. In this commentary we attempt to clarify the experimental design of that study. Based on a clearer understanding of the study procedures and data analysis we ropose some alternative interpretations of the results.

BACKGROUND: Ultrasound is used in the treatment of a wide variety of musculoskeletal disorders. OBJECTIVES: To evaluate the effects of ultrasound therapy in the treatment of acute ankle sprains. SEARCH STRATEGY: MEDLINE and EMBASE up to December 1998 and databases of the Cochrane Rehabilitation and Related Therapies Field and Musculoskeletal Injuries Group were searched. This was supplemented with citation tracking, and contact with colleagues. Date of the most recent search: April 1999. SELECTION CRITERIA: Randomised or pseudo-randomised trials were included in the review if the following conditions were met: at least one study group was treated with active ultrasound; the study included patients with acute lateral ankle sprains; and outcome measures included general improvement, pain, swelling, functional disability, or range of motion. Final selection of papers was conducted by two independent reviewers. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality using a standardised checklist, and extracted data. Whenever possible, the results were analysed on an intention-to-treat basis. Fixed odds ratios together with 95% confidence intervals were calculated for dichotomous outcomes, and weighted or, where different scales were used, standardised mean differences together with 95% confidence intervals for continuous outcome measures. Pooling of data was undertaken where there was clinical homogeneity in terms of subjects, treatments, outcomes, and follow-up time points. MAIN RESULTS: The four included trials, involving 514 patients, were only of modest methodological quality. None of the three placebo-controlled trials (sham ultrasound) could demonstrate statistically significant differences between true and sham ultrasound therapy for any outcome measure at seven days of follow-up. The pooled odds ratio for general improvement was 1.19 (Peto fixed effects model, 95% confidence interval 0.73 to 1.93) for the comparison between ultrasound and sham ultrasound. The differences between intervention groups were generally small, between 0 and 6% for most dichotomous outcomes. However, one trial reported relatively large differences for pain free status (20%) and swelling (25%) in favour of ultrasound treatment. REVIEWER'S CONCLUSIONS: The extent and quality of the available evidence for the effects of ultrasound therapy for acute ankle sprains are limited. The results of three placebo-controlled trials do not support the use of ultrasound in the treatment of ankle sprains. The magnitude of most reported treatment effects appeared to be small, and may be of limited clinical importance. As yet, only few trials are available and no conclusions can be made regarding an optimal and adequate dosage schedule for ultrasound therapy, and whether such a schedule would improve on the reported effectiveness of ultrasound for ankle sprains

The background of frequent attenders (FAs) of the General Practitioner (GP) often remains unclear. This thesis examines persistent frequent attendance, the relationship with (medical) conditions, methods to treat FAs, the impact of FAs on the GP’s workload and costs of healthcare, which medical file data may predict persistence of frequent attendance and whether treating anxiety and depression among FAs could be (cost)effective. We studied GP databases, followed prospectively a cohort of new FAs during 2 years and simulated in a Markov model a cohort of 10,000 FAs over a period of 5 years. Short-term and persistent FAs have respectively 2-4 times more problems and cost the GP 4 to 5 more time than non FAs. FAs, and persistent FAs, make more costs (respectively 1.157 and 3.593 Euros per year more than non FAs), which can be partly explained by registered diseases. Anxiety, life events and poor coping contribute to persistence of frequent attendance and may (partly) explain these increased costs. Analysis and intervention by the GP has proven to decrease FAs’ use of healthcare. Our simulation study suggests that detection and treatment of anxiety and depression in FAs will not be cost-effective.