Journal of Clinical Epidemiology - Articles in Press

Citation analysis of identical consensus statements revealed journal-related bias - Corrected Proof

Thomas V. Perneger — 2010-01-25

Abstract: Objective: To examine whether the prestige of a journal, measured by its impact factor, influences the numbers of citations obtained by published articles, independently of their scientific merit.Study Design and Setting: In this cohort study, citation counts were retrieved for articles describing consensus statements that were published in multiple journals and were correlated with the impact factors of the source journals.Results: Four consensus statements were published in multiple copies: QUOROM (QUality Of Reporting Of Meta-analyses) was published in three journals, CONSORT (CONsolidated Standards Of Reporting Trials) in eight journals, STARD (STAndards for Reporting of Diagnostic accuracy) in 14 journals, and STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) in eight journals. For each consensus statement, the impact factor of the source journal and the number of citations were highly correlated (Spearman correlation coefficients: QUOROM, 1.00; CONSORT, 0.88; STARD, 0.65; and STROBE, 0.81—all P<0.02). When adjusted for time since publication, each logarithm unit of impact factor predicted an increase of 1.0 logarithm unit of citations (95% confidence interval: 0.7–1.3, P<0.001), and the variance explained was 66% (adjusted r2=0.66).Conclusions: The prominence of the journal where an article is published, measured by its impact factor, influences the number of citations that the article will gather over time. Citation counts are not purely a reflection of scientific merit.

Appropriate statistical methods are required to assess diagnostic tests for replacement, add-on, and triage - Corrected Proof

Andrew Hayen, Petra Macaskill, Les Irwig, Patrick Bossuyt — 2010-01-18

Abstract: Objective: To explain which measures of accuracy and which statistical methods should be used in studies to assess the value of a new binary test as a replacement test, an add-on test, or a triage test.Study Design and Setting: Selection and explanation of statistical methods, illustrated with examples.Results: Statistical methods for comparative diagnostic accuracy studies are described that take into account the purpose of the new diagnostic test. Methods are described within a framework that defines the major purpose of test comparison: assessing the value of a new test as a replacement test, an add-on test, or a triage test. Methods appropriate for both unpaired and paired study designs for binary test data are given, including regression modeling of diagnostic test accuracy. Implications for efficient study designs are also discussed.Conclusions: Appropriate selection of existing statistical methods is necessary to address research questions about the comparative accuracy of new tests.

Mixed treatment comparison analysis provides internally coherent treatment effect estimates based on overviews of reviews and can reveal inconsistency - Corrected Proof

Deborah M. Caldwell, Nicky J. Welton, A.E. Ades — 2010-01-18

Abstract: Objectives: To propose methods for mixed treatment comparisons (MTC) based on pooled summaries of the type produced in overviews of reviews.Study Design and Setting: Overviews of reviews (umbrella reviews) summarize the results of multiple systematic reviews into a single document. They report the summary estimates from the original pairwise meta-analyses and discuss them in narrative form, with the intention of identifying the most effective treatment. We present methods for MTC synthesis, tailored for use with overviews of reviews. These generate a single internally consistent summary of all the relative treatment effects and assessments of whether the summary is consistent with the data. These methods are applied to a published overview of treatments for childhood nocturnal enuresis. We apply the methods to both fixed-effect (FE) and random-effects (RE) meta-analyses of the original trials.Results: The summary relative risks based on FE meta-analyses, as originally published, were highly inconsistent. Those based on RE meta-analyses were consistent and could, given standard assumptions on comparability of treatment effects in meta-analysis, form a basis for coherent decision making.Conclusion: Along with the summaries from systematic reviews, MTC methods should be used in overviews to provide a single coherent analysis of all treatment comparisons and to check for evidence consistency.

Disability, more than multimorbidity, was predictive of mortality among older persons aged 80 years and older - Corrected Proof

2010-01-08

Abstract: Objective: In this study, we evaluate the impact of disability and multimorbidity on the risk of all-cause death in a population of frail older persons living in community.Study Design and Setting: We analyzed data from the Aging and Longevity Study in the Sirente geographic area, a prospective cohort study that collected data on all subjects aged 80 years and older (n=364). The main outcome measure was all-cause mortality over 4-year follow-up.Results: A total of 150 deaths occurred. Sixty-seven subjects (44.6%) died in the nondisabled group compared with 83 subjects (55.3%) in the disabled group (P<0.01). Thirty-nine subjects (31.7%) died among subjects without multimorbidity compared with 111 subjects (46.0%) with two or more diseases (P<0.01). When examining the combined effect of multimorbidity and disability, the effect of disability on the risk of death was higher than that of multimorbidity. After adjusting for potential confounders, relative to those without disability and multimorbidity, disabled subjects showed an increased risk of death when multimorbidity was associated (hazard ratio [HR]=3.91; 95% confidence interval [CI]=1.53–10.00) and in absence of multimorbidity (HR=2.36; 95% CI=0.63–8.83).Conclusion: Our results show that disability exerts an important influence on mortality, independently of age and other clinical and functional variables.

Global Perceived Effect scales provided reliable assessments of health transition in people with musculoskeletal disorders, but ratings are strongly influenced by current status - Corrected Proof

2010-01-08

Abstract: Objective: The study investigated the test–retest reliability and construct validity of the Global Perceived Effect (GPE) scale in patients with musculoskeletal disorders.Study Design and Setting: Data from seven clinical studies including 861 subjects were used for the analyses. Repeat measures taken at the same attendance and from attendances separated by 24 hours were compared to estimate test–retest reliability. Construct validity was evaluated by examining relationships between pre, post, and change scores in pain and disability measures with GPE measures.Results: Intraclass correlation coefficient values of 0.90–0.99 indicate excellent reproducibility of the GPE scale. In all but one data set, change scores on pain and disability measures correlated well (r=0.40–0.74) with GPE; however, post scores nearly always correlated even more strongly (r=0.58–0.84), and pre scores showed much weaker association (r=0.00–0.28). Pre scores accounted for only a small amount of additional R2 when added to regression models including post score.Conclusions: Test–retest reliability of the GPE is excellent. GPE ratings are strongly influenced by current status, with the effect more obvious as transition time lengthens. This result questions whether transition ratings truly reflect change, or rather just current state. This finding also has implications for the use of GPE ratings as an external criterion of change in clinimetric studies.

Systematic reviews on tobacco control from Cochrane and the Community Guide: different methods, similar findings - Corrected Proof

Laura J. Rosen, Michal Ben Noach — 2010-01-08

Abstract: Objectives: To compare the methods and findings of systematic reviews (SRs) on common tobacco control interventions from two organizations: the Cochrane Collaboration (“Cochrane”) and the US Task Force for Community Preventive Services (“the Guide”).Study Design and Setting: Literature review. We retrieved all reviews pertaining to tobacco control produced by the Cochrane and the Guide. We identified seven common topics and compared methods and findings of the retrieved reviews.Results: There was considerable variability in the designs of included studies and methods of data synthesis. On average, Cochrane identified more studies than did the Guide (Mean 43.7 vs. 19.0), with only limited overlap between sets of included studies. Most Cochrane reviews (71.4%) were synthesized narratively, whereas most Guide reviews (85.7%) were synthesized using a median of effect size. Despite these differences, findings of the reviews yielded substantial agreement.Conclusion: Cochrane and the Guide conduct SRs on similar tobacco control-related topics differently. The SRs of the two organizations include overlapping, but nonidentical sets, of studies. Still, they usually reach similar conclusions. Identification of all pertinent original studies seems to be a weak point in the SR process. Policy makers should use reviews from both organizations in formulating tobacco control policy.

A nonparametric two-sample comparison for skewed data with unequal variances - Corrected Proof

Eva Skovlund — 2010-01-08

For practical situations, the pure shift model is probably not very realistic, and it is thus important to assess the robustness of different tests against deviations from this model. It is well established that heteroscedasticity (unequal variances) is at least as deleterious for the properties of the Wilcoxon-Mann-Whitney (WMW) test as for the t-test and that the Welch test should replace the t-test when distributions are approximately normal and variances unequal. It is also worth remembering that the WMW test does not share the asymptotic robustness properties of the t-test. In addition, unequal variance is not the only problem frequently encountered. Distributions can also be skewed, and the skewness of the two distributions may differ. Unfortunately, but not unexpectedly, even the Welch test is unable to maintain the nominal significance level when distributions are skewed .

A nonparametric two-sample comparison for skewed data with unequal variances - Corrected Proof

Markus Neuhäuser — 2010-01-08

Abstract: Objective: The aim of the study was to recommend a statistical test for the situation in which unequal variances are accompanied by skewed distributions. A previous publication in this journal could not recommend any test; instead, transformations were suggested.Study Design and Setting: A recently introduced generalized Wilcoxon test is presented, which can be applied when variances may be unequal and the distribution may be skewed. This test examines the null hypothesis that the relative effect is 0.5. Its type I error rate was investigated in a simulation study.Results: The generalized Wilcoxon test was already recommended for various areas of life sciences and, very recently, it was shown that a permutation test could be performed with the generalized test statistic. Simulation results indicate an acceptable control of the type I error rate even for extreme variance ratios.Conclusion: The generalized Wilcoxon test should be applied when it cannot be assumed that variances are equal and that the distribution is symmetric. This test is preferable to a transformation, because the use of transformations can be problematic, in particular when sample sizes are small.

Opening up the "Black Box": Metabolic phenotyping and metabolome-wide association studies in epidemiology - Corrected Proof

2010-01-08

Abstract: Background: Metabolic phenotyping of humans allows information to be captured on the interactions between dietary, xenobiotic, other lifestyle and environmental exposures, and genetic variation, which together influence the balance between health and disease risks at both individual and population levels.Objectives: We describe here the main procedures in large-scale metabolic phenotyping and their application to metabolome-wide association (MWA) studies.Methods: By use of high-throughput technologies and advanced spectroscopic methods, application of metabolic profiling to large-scale epidemiologic sample collections, including metabolome-wide association (MWA) studies for biomarker discovery and identification.Discussion: Metabolic profiling at epidemiologic scale requires optimization of experimental protocol to maximize reproducibility, sensitivity, and quantitative reliability, and to reduce analytical drift. Customized multivariate statistical modeling approaches are needed for effective data visualization and biomarker discovery with control for false-positive associations since 100s or 1,000s of complex metabolic spectra are being processed.Conclusion: Metabolic profiling is an exciting addition to the armamentarium of the epidemiologist for the discovery of new disease-risk biomarkers and diagnostics, and to provide novel insights into etiology, biological mechanisms, and pathways.

The development of a quality appraisal tool for studies of diagnostic reliability (QAREL) - Corrected Proof

Nicholas P. Lucas, Petra Macaskill, Les Irwig, Nikolai Bogduk — 2010-01-08

Abstract: Background and Objective: In systematic reviews of the reliability of diagnostic tests, no quality assessment tool has been used consistently. The aim of this study was to develop a specific quality appraisal tool for studies of diagnostic reliability.Methods: Key principles for the quality of studies of diagnostic reliability were identified with reference to epidemiologic principles, existing quality appraisal checklists, and the Standards for Reporting of Diagnostic Accuracy (STARD) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) resources. Specific items that encompassed each of the principles were developed. Experts in diagnostic research provided feedback on the items that were to form the appraisal tool. This process was iterative and continued until consensus among experts was reached.Results: The Quality Appraisal of Reliability Studies (QAREL) checklist includes 11 items that explore seven principles. Items cover the spectrum of subjects, spectrum of examiners, examiner blinding, order effects of examination, suitability of the time interval among repeated measurements, appropriate test application and interpretation, and appropriate statistical analysis.Conclusions: QAREL has been developed as a specific quality appraisal tool for studies of diagnostic reliability. The reliability of this tool in different contexts needs to be evaluated.

Effect of family history on the risk of varicose veins is affected by differential misclassification - Corrected Proof

2010-01-08

Abstract: Objective: We assessed differential misclassification in self-reported family history of varicose veins by comparing consistency of subject's own varicose vein status and the consistency of information on varicose veins in family members.Study Design and Setting: A population-based cohort study of 4,903 middle-aged residents of the city of Tampere, Finland. A questionnaire was used at entry and at the end of the 5-year follow-up.Results: The estimated prevalence of positive family history of varicose veins varied depending on subject's own varicose veins from odds ratio (OR) 0.14 (95% confidence interval [CI]=0.01–0.58), in those with varicose veins reported in the first but not the second survey to OR 6.0 (95% CI=2.0–47.8), in those with varicose veins reported in the second survey but not in the first. The incidence of varicose veins varied from 0.4 (95% CI=0.1–1.4) to 4.1 (95% CI=2.1–7.1) (per 100 person-years) depending how the proband memorized the family history.Conclusion: Results on the effect of family history on varicose veins are subject to bias, which reduces the credibility of the reports proposing a strong hereditary component of varicose veins.

Moving knowledge to action through dissemination and exchange - Corrected Proof

Michelle L. Gagnon — 2009-12-11

Abstract: Objective: The objective of this article is to discuss the knowledge dissemination and exchange components of the knowledge translation process that includes synthesis, dissemination, exchange, and ethically sound application of knowledge. This article presents and discusses approaches to knowledge dissemination and exchange and provides a summary of factors that appear to influence the effectiveness of these processes. It aims to provide practical information for researchers and knowledge users as they consider what to include in dissemination and exchange plans developed as part of grant applications.Study Design and Setting: Not relevant.Results and Conclusions: Dissemination is targeting research findings to specific audiences. Dissemination activities should be carefully and appropriately considered and outlined in a dissemination plan focused on the needs of the audience who will use the knowledge. Researchers should engage knowledge users to craft messages and help disseminate research findings. Knowledge brokers, networks, and communities of practice hold promise as innovative ways to disseminate and facilitate the application of knowledge. Knowledge exchange or integrated knowledge translation involves active collaboration and exchange between researchers and knowledge users throughout the research process.

The Kaiser Permanente inpatient risk adjustment methodology was valid in an external patient population - Corrected Proof

Carl van Walraven, Gabriel J. Escobar, John D. Greene, Alan J. Forster — 2009-12-11

Abstract: Objectives: Accurately predicting hospital mortality is necessary to measure and compare patient care. External validation of predictive models is required to truly prove their utility. This study assessed the Kaiser Permanente inpatient risk adjustment methodology for hospital mortality in a patient population distinct from that used for its derivation.Study Design and Setting: Retrospective cohort study at two hospitals in Ottawa, Canada, involving all inpatients admitted between January 1998 and April 2002 (n=188,724). Statistical models for inpatient mortality were derived on a random half of the cohort and validated on the other half.Results: Inpatient mortality was 3.3%. The model using original parameter estimates had excellent discrimination (c-statistic 89.4, 95% confidence interval [CI] 0.891–0.898) but poor calibration. Using data-based parameter estimates, discrimination was excellent (c-statistic 0.915, 95% CI 0.912–0.918) and remained so when patient comorbidity was expressed in the model using the Elixhauser Index (0.901, 0.898–0.904) or the Charlson Index (0.894, 0.891–0.897). These models accurately predicted the risk of hospital death.Conclusion: The Kaiser Permanente inpatient risk adjustment methodology is a valid model for predicting hospital mortality risk. It performed equally well regardless of methods used to summarize patient comorbidity.

Patient preferences before and after total knee arthroplasty - Corrected Proof

2009-12-11

Abstract: Objective: Patients before total joint arthroplasty vary in the spectrum and importance of their concerns. The objectives of this study were to evaluate the psychometric properties of the Knee Patient-Specific Index (KPSI) and to determine the type and importance of patients' concerns before and after knee arthroplasty.Study Design and Setting: A cohort of 119 patients scheduled for elective primary (or revision) total knee arthroplasty were interviewed at two tertiary care teaching hospitals. Patients also completed the Knee Society Scale (KSS), the Short Form 36, the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR).Results: Patients improved after total knee arthroplasty in all 42 symptoms and physical limitations, except crouching/kneeling and walking up and down stairs. Patients' summated concerns correlated with the WOMAC pain subscale (ranging from 0.72 to 0.79), WOMAC physical function subscale (ranging from 0.72 to 0.76), and KSS (ranging from 0.28 to 0.39). The summated responses changed after knee arthroplasty as demonstrated by the standardized response mean of 1.1.Conclusions: The KPSI captures individual patient unique preferences for patients undergoing total knee arthroplasty. Patients improved in virtually all aspects of their symptoms and function after surgery, with the exception of crouching/kneeling and knee feeling hot.

Allocation concealment continues to be misunderstood - Corrected Proof

Vance W. Berger, Anh-Chi Do — 2009-12-11

Foley et al. lamented the fact that allocation concealment is described inadequately in two-thirds of the studies, but the flip side of this is the solace that one can take in knowing that at least allocation concealment is described adequately in one-third of the studies. Of course, Foley et al. also pointed out that allocation concealment continues to be misunderstood by many investigators, and we would like to echo this sentiment. In fact, it seems to be true even more than Foley et al. themselves recognize, and there is a particular irony here, a point to which we will return shortly. Foley et al. considered the reporting of allocation concealment to be adequate “if the authors clearly reported a mechanism through which it could be reasonably ascertained that the investigators had no foreknowledge of the treatment assignments.”

Allocation concealment continues to be misunderstood - reply - Corrected Proof

Norine C. Foley, Mark Speechley — 2009-12-08

We would like to thank Drs. Berger and Do for making us aware of Berger's work, which includes approaches for the prevention, detection, and statistical adjustment of the effects of third-order residual selection bias because of lack of concealed allocation (CA) in randomized trials . Having now acquainted ourselves with his work, we believe that our two groups probably share many values and beliefs. At a general level, we share a profound respect for the scientific method, including the necessity of observing proper methodology. More specifically, we share an interest in the problematic issue of CA in clinical trials. And finally, we would likely agree that CA is frequently misunderstood by authors and, by implication, editors and reviewers.

Expectations, validity, and reality in pharmacogenetics - Corrected Proof

Nita A. Limdi, David L. Veenstra — 2009-12-08

Abstract: In this review, we discuss the potential expectations, validity, predictive ability, and reality of pharmacogenetics in (1) titration of medication dose, (2) prediction of intended (efficacy) drug response, and (3) dose prediction of unintended (adverse) drug response. We expound on what these potential genetic predictors tell us and, more importantly, what they cannot tell us.Although pharmacogenetic markers have been hailed as promising tools, these proclamations are based mainly on associations rather than their evaluation as predictors. To put the expectations of the promise of pharmacogenetics in a realistic perspective, we review three examples. First, warfarin pharmacogenetics, wherein although the validity of the genetic variant dose is established and there is a validity of genetic variant–hemorrhage association, the clinical utility of testing is not clear. Second, the strong and clinically relevant HLA–Stevens–Johnson syndrome/toxic epidermal necrolysis association highlights the role of ethnicity. Third, the influence of CYP2D6 on tamoxifen efficacy, a model candidate with potential clinical utility but unclear validity.These examples highlight both the challenges and opportunities of pharmacogenomics. First, establishing a valid association between a genetic variation and drug response; second, doing so for a clinically meaningful outcome; and third, providing solid evidence or rationale for improvement in patient outcomes compared with current standard of care.

A new graph and scoring system simplified analysis of changing states: disease remissions in a rheumatoid arthritis clinical trial - Corrected Proof

2009-12-07

Abstract: Background: In the setting of multiple remission and relapse periods of a chronic disease, simple endpoint analysis does not fully capture all relevant information, and we need methods to additionally describe both the duration of remission as well as the interruptions in this desired state. Probably the two-state continuous Markov process model comprises the best mathematical approach to data analysis. However, this approach is complex and not intuitive to clinicians. In this paper we propose a simple scoring system and a graph that can enhance the information about the remission experience in a trial or cohort study.Methods: The continuity rewarded (‘ConRew’) score sums up periods in remission, and rewards extended periods by placing more value on uninterrupted periods than on interrupted periods. The ‘patient vector graph’ attempts to plot each patient's remission experience over time as a horizontal line (the ‘vector’) that is visible when the patient is in remission, but interrupted whenever relapse occurs. In this way a pattern is formed that conveys the number of patients experiencing remission, their individual total duration and interruptions, and time when these occur.Results: In a dataset of a randomized trial in early rheumatoid arthritis, the graph clearly showed both early and late benefit of one group over the other. The scoring system demonstrated the main benefit was in the number of remission periods, not in their ‘uninterruptedness’.Conclusion: Both approaches proved feasible and added extra information.

Interim analysis in randomized trials: DAMOCLES' sword? - Corrected Proof

Marc G.H. Besselink, Yolanda van der Graaf, Hein G. Gooszen — 2009-12-04

Dr. Giard effectively summarizes the difficulties a Data Safety Monitoring Committee (DSMC) faces when deciding whether or not to terminate a trial early. We can comply with the suggested decision matrix by Knottnerus and Spigt, but feel that this matrix should be predefined in the study protocol. Furthermore, we and many others feel that a DSMC should take additional information into account as well. Pocock stated: “Negative stopping decisions cannot simply be based on statistical guidelines. For instance, if negative interim data are in contradiction with previous, more positive evidence, then the quality, extent, and relevance of that evidence will influence one's judgment” . In 2005, the DAMOCLES guidelines on clinical trial data monitoring committees stated: “Statistical issues should be only one of several considerations that a DMC needs to take into account. Other considerations include the balance of primary risks and benefits, the internal consistency of results, the consistency with, and nature of, external evidence, and the likelihood that the results would affect clinical practice. Statistical criteria (often called stopping rules) should be agreed in advance and regarded as guidelines for recommending stopping rather than rules” .

High agreement of self-report and physician-diagnosed somatic conditions yields limited bias in examining mental–physical comorbidity - Corrected Proof

Harald Baumeister, Levente Kriston, Jürgen Bengel, Martin Härter — 2009-12-04

Abstract: Objective: To quantify the misclassification bias of self-reported somatic diseases and its impact on the estimation of comorbidity with mental disorders.Study Design and Setting: Data were drawn from the German National Health Interview and Examination Survey (N=7,124), which assessed both self-reported and physician-diagnosed somatic diseases. Eight chronic diseases were examined: coronary heart disease, heart failure, asthma, chronic bronchitis, diabetes, cancer, arthrosis, and arthritis. Mental disorders were assessed by means of the Munich-Composite International Interview.Results: The agreement of case ascertainment by patient self-report and physician diagnosis was high (kappa: 0.74–0.92), except for arthritis (0.53). False-positive and false-negative disease statuses were partly associated with age, sex, socioeconomic status, somatic comorbidities, marital status, and mood and anxiety disorders. In most conditions, the odds ratios (ORs) of comorbid mental disorders based on self-reported diseases were slightly overestimated with regard to mood disorders (relative OR: 0.91–1.38), whereas there proved to be no such trend regarding anxiety disorders (0.82–1.05). Substance disorders were partly biased without showing an interpretable trend across diseases (0.49–2.58).Conclusions: Evaluation of mental–physical comorbidity based on self-reported and physician-diagnosed physical conditions yielded similar results, with modestly inflated ORs for mood disorders for several self-reported physical conditions.

Good agreement between parental and self-completed questionnaires about allergic diseases and environmental factors in teenagers - Corrected Proof

Linnea Hedman, Anders Bjerg, Matthew Perzanowski, Eva Rönmark — 2009-12-04

Abstract: Objectives: To study whether the methodological change from parent to index subject as questionnaire respondent affected the prevalence estimates and risk factor patterns for allergic diseases in a longitudinal study.Study Design and Setting: A prospective study of asthma and allergic diseases among children was begun in 1996 within the Obstructive Lung Disease in Northern Sweden Study. In 2002, about 3,342 (95% of invited) teenagers (13 to 14 years) completed the annual questionnaire. A random sample of 294 (84% of invited) parents also completed the same extended International Study of Asthma and Allergies in Childhood questionnaire. Skin prick tests were performed in 1996 and 2000.Results: There were no significant differences in the prevalence of rhinitis, eczema, or related environmental factors between parental and self-reports, except for the question of having a dog at home. The absolute agreement was high, whereas the kappa values were fair or moderate. Kappa values of questions regarding parental smoking were 0.8–0.9. Allergic sensitization was the major risk factor for both rhinitis and eczema, and the odds ratios were similar regardless of who reported the condition.Conclusion: The agreement between the parental and teenagers' reports was good, and the methodological change did not affect the study results.

ICD-10 hospital discharge diagnosis codes were sensitive for identifying pulmonary embolism but not deep vein thrombosis - Corrected Proof

2009-12-04

Abstract: Objective: To estimate the sensitivity of International Classification of Diseases, Tenth revision (ICD-10) hospital discharge diagnosis codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE).Study Design and Setting: We compared predefined ICD-10 discharge diagnosis codes with the diagnoses that were prospectively recorded for 1,375 patients with suspected DVT or PE who were enrolled at 25 hospitals in France. Sensitivity was calculated as the percentage of patients identified by predefined ICD-10 codes among positive cases of acute symptomatic DVT or PE confirmed by objective testing.Results: The sensitivity of ICD-10 codes was 58.0% (159 of 274; 95% CI: 51.9, 64.1) for isolated DVT and 88.9% (297 of 334; 95% CI: 85.6, 92.2) for PE. Depending on the hospital, the median values for sensitivity were 57.7% for DVT (interquartile range, IQR, 48.6–66.7; intracluster correlation coefficient, 0.02; P=0.31) and 88.9% for PE (IQR, 83.3–96.3; intracluster correlation coefficient, 0.11; P=0.03). The sensitivity of ICD-10 codes was lower for surgical patients and for patients who developed PE or DVT while they were hospitalized.Conclusion: ICD-10 discharge diagnosis codes yield satisfactory sensitivity for identifying objectively confirmed PE. A substantial proportion of DVT cases are missed when using hospital discharge data for complication screening or research purposes.

Most of the Quality of Life in Essential Tremor Questionnaire (QUEST) psychometric properties resulted in satisfactory values - Corrected Proof

2009-12-04

Abstract: Objective: This study sought to assess the psychometric attributes of the Quality of Life in Essential Tremor Questionnaire (QUEST) by undertaking an independent validation.Study Design and Setting: This was an observational, multicenter, cross-sectional study carried out in Neurology Departments of general hospitals. The following assessments were applied: Louis Rating Scale, Clinical Assessment of Tremor, Clinical Global Impression of Severity (CGI-ET), Hospital Anxiety and Depression Scale (HADS), EQ-5D, and QUEST (Spanish version).Results: One hundred and eighteen consecutive patients were included. According to the CGI-ET, most of patients had mild (42.4%) or moderate (43.2%) impact of tremor on performing daily activities. Fully computable QUEST data were 60.2%. The QUEST Summary Index (QUEST-SI) displayed marginal floor or ceiling effect. On the whole, QUEST internal consistency and reproducibility were satisfactory (Cronbach's alpha values: 0.73–0.86; QUEST-SI intraclass correlation coefficient: 0.77). Factor analysis identified eight factors (73.6% of the variance) that could be grouped into six, relatively coincident with the questionnaire's dimensions. The QUEST-SI correlated moderately with the EQ-5D index (rS=−0.40), HADS—Depression (rS=0.39), and CGI-ET (rS=0.39), and strongly with the QUEST scale for self-evaluation of tremor severity (rS=0.63). The standard error of measurement was 8.00.Conclusion: Apart from a substantial problem of acceptability, most of the tested psychometric attributes of the QUEST resulted satisfactory.

A valid and reliable belief elicitation method for Bayesian priors - Corrected Proof

2009-11-19

Abstract: Objective: Bayesian inference has the advantage of formally incorporating prior beliefs about the effect of an intervention into analyses of treatment effect through the use of prior probability distributions or “priors.” Multiple methods to elicit beliefs from experts for inclusion in a Bayesian study have been used; however, the measurement properties of these methods have been infrequently evaluated. The objectives of this study were to evaluate the feasibility, validity, and reliability of a belief elicitation method for Bayesian priors.Study Design and Setting: A single-center, cross-sectional study using a sample of academic specialists who treat pulmonary hypertension patients was conducted to test the feasibility, face and construct validity, and reliability of a belief elicitation method. Using this method, participants expressed the probability of 3-year survival with and without warfarin. Applying adhesive dots or “chips,” each representing 5% probability, in “bins” on a line, participants expressed their uncertainty and weight of belief about the effect of warfarin on 3-year survival.Results: Of the 12 participants, 11 (92%) reported that the belief elicitation method had face validity, 10 (83%) found the questions clear, and 11 (92%) found the response option easy to use. The median time to completion was 10 minutes (5–15 minutes). Internal validity testing found moderate agreement (weighted kappa=0.54–0.57). The intraclass correlation coefficient for test–retest reliability was 0.93.Conclusion: This method of belief elicitation for Bayesian priors is feasible, valid, and reliable. It can be considered for application in Bayesian clinical studies.

Mind the MIC: large variation among populations and methods - Corrected Proof

2009-11-19

Abstract: Objective: There is no consensus on the best method to determine the minimal important change (MIC) of patient-reported outcomes. Recent publications recommend the use of multiple methods. Our aim was to assess whether different methods lead to consistent values for the MIC.Study Design and Setting: We used two commonly used anchor-based methods and three commonly used distribution-based methods to determine the MIC of the subscales: pain and physical functioning of the Western Ontario and McMaster University Osteoarthritis Index questionnaire in five different studies involving patients with hip or knee complaints. We repeated the anchor-based methods using relative change scores, to adjust for baseline scores.Results: We found large variation in MIC values by the same method across studies and across different methods within studies. We consider it unlikely that this variation can be explained by differences between disease groups, disease severity, or lengths of follow-up. The variation persisted when using relative change scores. It was not possible to conclude whether this variation is because of true differences in MIC values between populations or to conceptual and methodological problems of the MIC methods.Conclusion: To better disentangle these two possible explanations, the MIC methodology should be improved and standardized. In the meantime, caution is needed when interpreting and using published MIC values.

Knowledge translation is the use of knowledge in health care decision making - Corrected Proof

Sharon E. Straus, Jacqueline M. Tetroe, Ian D. Graham — 2009-11-18

Abstract: Objective: To provide an overview of the science and practice of knowledge translation.Study Design: Narrative review outlining what knowledge translation is and a framework for its use.Results: Knowledge translation is defined as the use of knowledge in practice and decision making by the public, patients, health care professionals, managers, and policy makers. Failures to use research evidence to inform decision making are apparent across all these key decision maker groups. There are several proposed theories and frameworks for achieving knowledge translation. A conceptual framework developed by Graham et al., termed the knowledge-to-action cycle, provides an approach that builds on the commonalities found in an assessment of planned action theories.Conclusions: Review of the evidence base for the science and practice of knowledge translation has identified several gaps including the need to develop valid strategies for assessing the determinants of knowledge use and for evaluating sustainability of knowledge translation interventions.

The predictors of self-rated health and the relationship between self-rated health and health service needs are similar across socioeconomic groups in Canada - Corrected Proof

Peter M. Smith, Richard H. Glazier, Lyn M. Sibley — 2009-11-18

Abstract: Objective: To examine if there are systematic differences in the predictors of self-rated health (SRH) and to examine the relationship between SRH and health care utilization across socioeconomic groups.Study Design and Setting: We used cross-sectional data from the Canadian Community Health Survey linked to the Ontario Health Insurance Plan (N=17,109). We examined relative differences in the factors associated with different levels of SRH across socioeconomic groups (as assessed by education and household income) using probit models separately for men and women. We then examined differences in expected health care costs, as assessed by adjusted clinical group weights using administrative health care records, between socioeconomic groups within the same level of SRH.Results: We found limited differences across the predictive ability of a broad range of physical, mental, health service/care utilization, and health behavior variables on SRH across socioeconomic groups. In addition, no differences were found in the expected health care utilization costs across socioeconomic groups within the same level of SRH.Conclusions: The results of this study suggest that SRH assesses a broad variety of factors, including physical health status, mental health status, health service/care utilization, and health behaviors, relatively equally across socioeconomic groups, measured as either education or income.

A selection strategy was developed for fracture reduction programs in frail older people - Corrected Proof

2009-11-18

Abstract: Objectives: The aims of this study were to develop and evaluate a simple index for assessing the risk of fractures after a fall and to propose a selection strategy for identifying elderly individuals at high risk of both falls and fall-related fractures.Study Design and Setting: Two thousand five institutionalized older men and women were assessed for clinical risk factors and then followed up for falls and fall-related fractures for up to 2 years.Results: Our fracture risk index is derived from seven previously identified significant independent risk factors: weight, lower leg length, balance, cognitive function, type of institution, fracture history, and falls in the past year. The fracture rate was 6.5 times greater in the one-sixth of the falls with the highest index (9.7/100 falls) than in the lowest sixth (1.5/100 falls). Our proposed approach (based on balance, risk of falls, and the fracture risk index) selected a group of older people with high risk of both falls and fall-related fracture. The fracture incidence rate was 144% higher, and the falls incidence rate was 31% higher in the selected residents than in the remainder.Conclusion: The index could help rationalize fracture prevention programs for frail older people.

Cross-sectional reporting of previous Cesarean birth was validated using longitudinal linked data - Corrected Proof

2009-11-18

Abstract: Objective: The aim of this study was to demonstrate the feasibility of using linked health records to assess data quality in population health data.Study Design and Setting: Reproductive histories of 155,897 women were constructed by longitudinal linkage of the New South Wales (Australia) birth records in 1998–2005, and 127,952 birth and hospital discharge records in 2000–2005 were cross-sectionally linked. History of Cesarean section (CS) derived from the longitudinal linkage (“gold standard”) was used to validate the CS history fields (i.e., “Was the last birth by Cesarean section?” and “Total number of previous Cesarean sections?”) in birth records and to validate “vaginal birth after previous Cesarean (VBAC)” and “maternal care for uterine scar” in hospital records.Results: The reporting of CS at last birth was reliable with sensitivity, specificity, positive predictive value (PPV), and negative predictive value all >95% as was the number of previous CS (weighted kappa=0.97). For the hospital data, sensitivity and PPV were 46% and 99% for VBAC, 92% and 99% for maternal care of uterine scar, and 85% and 99%, respectively, for any prior CS.Conclusion: Assessing data quality by record linkage is feasible and can be done more quickly and cheaply than by any traditional validation study.

Validation of an improved area-based method of calculating general practice–level deprivation - Corrected Proof

Thomas Griffin, Tim J. Peters, Debbie Sharp, Chris Salisbury, Sarah Purdy — 2009-11-16

Abstract: Objective: To compare the methods of calculating practice deprivation scores in the absence of patient-level data.Study Design and Setting: Three methods of deriving general practice deprivation scores without patient-level data were compared against “gold standard” patient-level scores in 226 English practices. The three methods were lower super output area (LSOA), middle super output area (MSOA), and a geographical information systems (GIS) method. Working, if necessary, on the log scale, agreement between scores was assessed using Bland and Altman's method, Kappa statistics, and Pitman's test.Results: Based on the antilog 95% limits of agreement from Bland–Altman plots, GIS methods showed least variation compared with gold standard (0.66–1.47), followed by MSOA (0.61–1.70) and LSOA (0.38–2.29) methods. The differences in variances between both GIS and MSOA, and LSOA and MSOA comparisons, were greater than would be expected by chance (Pitman's P<0.001). High levels of agreement (kappa: 0.93, 0.86, and 0.80) were observed between GIS, MSOA, and LSOA methods compared with the “gold standard.”Conclusion: In situations where patient postcodes are unavailable, the GIS method is superior to area-based methods. However, where the GIS method cannot readily be applied, the MSOA method should be used in preference to the LSOA method.

The Italian version of the Lower Extremity Functional Scale was reliable, valid, and responsive - Corrected Proof

2009-11-13

Abstract: Objective: To determine the measurement properties of an Italian Version of the Lower Extremity Functional Scale (LEFS) in patients with lower extremity musculoskeletal dysfunction.Study Design and Setting: This is a prospective methodological study of repeated measures with a sample of 250 consecutive patients. Reliability, validity, and responsiveness were evaluated.Results: The Italian version of the LEFS showed a high degree of internal consistency with a Cronbach alpha of 0.94 (95% confidence interval [CI]: 0.91, 0.96). The test–retest reliability was high for both intra-interviewer and inter-interviewer measures with an ICC(2,1 and 2,k) of 0.91 (95% CI: 0.86, 0.93) and 0.89 (95% CI: 0.83, 0.91), respectively. The LEFS showed a better correlation with the 36-Item Short-Form Health Survey (SF-36) physical component summary score rather than with the SF-36 mental component summary score both at the initial assessment (r=0.61 and 0.26, respectively) and at the discharge (r=0.72 and 0.22, respectively). Receiver operating characteristic curve analysis revealed a large responsiveness for the LEFS (area under the curve [AUC]=0.97) and a moderate responsiveness for the SF-36 (AUC=0.68).Conclusion: The Italian version of the LEFS is a valid, reliable, and responsive tool that can be used to measure function in Italian patients with lower extremity musculoskeletal dysfunction.

Pictogram use was validated for estimating individual's body mass index - Corrected Proof

2009-11-13

Abstract: Objective: We designed this study to assess the validity and reliability of pictogram for estimating body mass index (BMI).Study Design and Setting: Participants of Golestan cohort study during 2000–2004 were recruited in this study. Demographic and anthropometric information (weight, height, and BMI) were collected on all participants. A set of drawings (pictogram) ranging from very lean to obese were used to assess the individual's perception of their body size. Sensitivity and specificity of each pictogram score were calculated and cutoff points were determined using sensitivity/specificity plots. We used receiver operating characteristic curves to assess the validity of pictogram scores.Results: Of the 15,437 subjects enrolled in the study, 6,574 (42.6%) were males and 8,863 (57.4%) were females. Their mean±standard deviation age was 52.58±9.28 years. Pictogram scores 1, 2, and 3 were assigned to normal participants; pictogram score 4 was selected by overweight subjects, and finally, pictogram scores equal or higher than 5 were selected by obese ones (area under curve: 0.83–0.85).Conclusion: According to our results, pictogram is a valid measure for discriminating obese or overweight from normal individuals, and for distinguishing obese from overweight or normal individuals. So it can be concluded that body image pictogram is valid for discriminating normal and obese individuals.

BLISS index using WOMAC index detects between-group differences at low-intensity symptom states in osteoarthritis - Corrected Proof

2009-11-09

Abstract: Objectives: The ability of the Bellamy et al. Low-Intensity Symptom State-attainment (BLISS) Index to differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis was explored using the stiffness, function, and total index (TI) components of the WOMAC.Study Design and Setting: Six different BLISS measures were analyzed using five WOMAC score thresholds: ≤5 normalized units (NUs): ≤10, ≤15, ≤20, and ≤25 (lower=better health).Results: More patients in the hylan G-F 20 group achieved BLISS states in all three WOMAC subscales for all six BLISS analyses. These differences were statistically significant for the BLISS response at any time at all threshold levels except ≤5NU.Conclusions: The six BLISS measures and threshold levels of stiffness, function, and TI score were able to statistically discriminate between treatment groups. BLISS-10 is a therapeutically attainable very low symptom state at which clinically important statistically significant between-group differences are detectable in pain, stiffness, function, and TI score and therefore may provide a benchmark against which therapeutic interventions can be assessed. However, the value to patients of these symptom states requires further elaboration.

Correspondence analysis is a useful tool to uncover the relationships among categorical variables - Corrected Proof

2009-11-09

Abstract: Objective: Correspondence analysis (CA) is a multivariate graphical technique designed to explore the relationships among categorical variables. Epidemiologists frequently collect data on multiple categorical variables with the goal of examining associations among these variables. Nevertheless, CA appears to be an underused technique in epidemiology. The objective of this article is to present the utility of CA in an epidemiological context.Study Design and Setting: The theory and interpretation of CA in the case of two and more than two variables are illustrated through two examples.Results: The outcome from CA is a graphical display of the rows and columns of a contingency table that is designed to permit visualization of the salient relationships among the variable responses in a low-dimensional space. Such a representation reveals a more global picture of the relationships among row–column pairs, which would otherwise not be detected through a pairwise analysis.Conclusion: When the study variables of interest are categorical, CA is an appropriate technique to explore the relationships among variable response categories and can play a complementary role in analyzing epidemiological data.

Outpatient urticaria diagnosis codes have limited predictive value for same-day influenza vaccine adverse event detection - Corrected Proof

2009-11-05

Abstract: Objectives: To assess the predictive value of claims-based outpatient urticaria diagnosis codes to identify potential vaccine-related adverse events (AEs) when recorded on the same day as influenza vaccination.Study Design and Setting: Health plan members with outpatient claims for influenza vaccination and urticaria on the same day between October 1, 2002, and December 31, 2007, were eligible for inclusion. Electronic medical records (EMRs) for 50 eligible patients with the most recent visits of interest occurring at a large group practice were sampled for review.Results: EMRs were available and reviewed for 42 of 50 patients. An influenza vaccination was confirmed in all reviewed medical charts. Urticaria occurring on the day of influenza vaccination was confirmed for 40% of participants (17/42); 3 confirmed urticaria diagnoses were potential AEs and 14 urticaria events occurred before vaccination. Among those with unconfirmed diagnoses, 17 had no evidence of urticaria on physical examination on the day of interest (4 had evidence of a nonurticarial rash and 13 had no evidence of rash on examination) and 8 had insufficient information to make a clinical determination.Conclusion: Outpatient diagnosis codes for urticaria found in health insurance claims data are limited in their predictive value to identify same-day vaccine AEs.

Successful high-quality knowledge translation research: three case studies - Corrected Proof

Sumit R. Majumdar — 2009-11-05

Articles in this series have examined aspects of knowledge translation in detail, including various theoretical frameworks, types of interventions, implementation methods, issues related to measurement and evaluation of processes and outcomes of care, and the strengths and limitations of various study designs. This article draws upon what has come before and presents some “case studies” of high-quality and successful knowledge-to-action studies. The case studies (Kiefe et al. , examining the use of achievable benchmarks with audit and feedback to improve multiple processes of care for patients with diabetes; Kucher et al. , examining decision support and prompts for improving care of hospitalized patients at risk of thromboembolism; and Gonzales et al. , looking at a multifaceted intervention to decrease antibiotic prescribing for respiratory tract infections in the community) have in common that they addressed common and clinically important problems where the established evidence was already very strong and directed efforts at changing health professional patterns of practice.

Construction of drug treatment episodes from drug-dispensing histories is influenced by the gap length - Corrected Proof

2009-11-02

Abstract: Objectives: When constructing drug treatment episodes using drug-dispensing databases, duration and the number of prescriptions belonging to a single treatment episode need to be defined. We investigated how different methods used to construct antidepressant treatment episodes influence their median estimated length.Study Design and Setting: A follow-up study among adult antidepressant drug users, identified from the Dutch PHARMO RLS, starting selective serotonin reuptake inhibitor (SSRI) use in 2001 was conducted. The influence of varying lengths of the prescription overlap and the gap between prescriptions (number of days or percentage of prescription duration) on the median antidepressant treatment episode length were investigated.Results: Of the 16,053 SSRI starters, 65.1% were female and mean age was 45.7 (SD: 17.2) years. Median antidepressant treatment episode length doubled when the gap length was expanded from 0 to 10 days. For short gap lengths the episode interquartile range was 40% to 200% larger when overlap was accounted for and when percentage of prescription duration gap length was used.Conclusion: Differences in median episode length exist between methods that account for or disregard prescription overlap. These differences are of importance for studies that focus on drug exposure-outcome relationships and could have consequences for epidemiological analysis.

Real-world effectiveness of new medicines should be evaluated by appropriately designed clinical trials - Corrected Proof

Nick Freemantle, Thomas Strack — 2009-11-02

Abstract: Objectives: Health care providers, policy makers, and importantly patients themselves are increasingly interested in the outcomes of clinical trials yet often expect different questions to be addressed than those commonly asked in conventional phase 3 trials.Study Design and Setting: Review of methodological articles.Results: Conventional randomized controlled trials (RCTs) emphasize internal validity through standardization and control but by design reduce external validity, that is, generalizability of results and conclusions. Ongoing uncertainty about effectiveness or safety of medical interventions in the real world is the major driver for developing improved phase 3b and phase 4 study designs. Factors that should improve the relevance of these real-world trials (RWTs) include choice of endpoints; investigator specialty, appropriate patient selection criteria; emphasis on patient–physician interaction; admittance of relevant interventions in all study groups; and more flexible, simple, and possibly event-driven study visits and procedures, while maintaining randomization as a critical element to address confounders.Conclusion: Although we do not believe that RWTs will supplant conventional RCTs, properly designed RWTs will enrich our understanding of the effectiveness of new health care interventions and better inform patients and health care providers alike.

The use of an item response theory–based disability item bank across diseases: accounting for differential item functioning - Corrected Proof

Nadine Weisscher, Cees A. Glas, Marinus Vermeulen, Rob J. De Haan — 2009-11-02

Abstract: Objective: There is not a single universally accepted activity of daily living (ADL) instrument available to compare disability assessments across different patient groups. We developed a generic item bank of ADL items using item response theory, the Academic Medical Center Linear Disability Scale (ALDS). When comparing outcomes of the ALDS between patients groups, item characteristics of the ALDS should be comparable across groups. The aim of the study was to assess the differential item functioning (DIF) in a group of patients with various disorders to investigate the comparability across these groups.Study Design and Setting: Cross-sectional, multicenter study including 1,283 in- and outpatients with a variety of disorders and disability levels. The sample was divided in two groups: (1) mainly neurological patients (n=497; vascular medicine, Parkinson's disease and neuromuscular disorders) and (2) patients from internal medicine (n=786; pulmonary diseases, chronic pain, rheumatoid arthritis, and geriatric patients).Results: Eighteen of 72 ALDS items showed statistically significant DIF (P<0.01). However, the DIF could effectively be modeled by the introduction of disease-specific parameters.Conclusion: In the subgroups studied, DIF could be modeled in such a way that the ensemble of the items comprised a scale applicable in both groups.

Cascade effects of laboratory testing are found to be rare in low disease probability situations: prospective cohort study - Corrected Proof

Paul H.H. Houben, Trudy van der Weijden, Ron A.G. Winkens, Richard P.T.M. Grol — 2009-11-02

Abstract: Objectives: (1) To investigate the frequency of cascades of further diagnostic investigations and referrals after abnormal laboratory results in situations of low disease probability; (2) to investigate pretest and posttest determinants; and (3) to describe the cascades that occur.Study Design and Setting: Prospective cohort study in primary care in The Netherlands. Numbers of investigations/referrals were recorded during 6 months of follow-up for 256 patients with normal and abnormal laboratory results. The influences of the reason for ordering tests, interpretation of results, and pretest/posttest disease probability were examined.Results: After receiving the laboratory results, the physicians ordered further investigations for 22 (17.3%) patients with abnormal results and for two (1.6%) patients with normal results (P<0.001). They referred 12 (9.4%) patients with abnormal results and eight (6.2%) patients with normal results (P=0.33). Six patients had two investigations and/or referrals, and one patient had three referrals. There were significantly more investigations/referrals for results interpreted as abnormal (P=0.004) and for cases with a high posttest disease probability (P=0.001).Conclusion: This study suggests that cascade processes after laboratory testing in situations of low disease probability are limited in magnitude and frequency. Improving interpretations may help improve the appropriateness of further investigations and referrals.

A comparison of ad hoc methods to account for non-cancer AIDS and deaths as competing risks when estimating the effect of HAART on incident cancer AIDS among HIV-infected men - Corrected Proof

2009-11-02

Abstract: Objective: To compare three ad hoc methods to estimate the marginal hazard of incident cancer acquired immune deficiency syndrome (AIDS) in a highly active antiretroviral therapy (1996–2006) relative to a monotherapy/combination therapy (1990–1996) calendar period, accounting for other AIDS events and deaths as competing risks.Study Design and Setting: Among 1,911 human immunodeficiency virus (HIV)-positive men from the Multicenter AIDS Cohort Study, 228 developed cancer AIDS and 745 developed competing risks in 14,202 person-years from 1990 to 2006. Method 1 censored competing risks at the time they occurred, method 2 excluded competing risks, and method 3 censored competing risks at the date of analysis.Results: The age, race, and infection duration adjusted hazard ratios (HRs) for cancer AIDS were similar for all methods (HR≈0.15). We estimated bias and confidence interval coverage of each method with Monte Carlo simulation. On average, across 24 scenarios, method 1 produced less-biased estimates than methods 2 or 3.Conclusions: When competing risks are independent of the event of interest, only method 1 produced unbiased estimates of the marginal HR, although independence cannot be verified from the data. When competing risks are dependent, method 1 generally produced the least-biased estimates of the marginal HR for the scenarios explored; however, alternative methods may be preferred.

A correspondence analysis revealed frailty deficits aggregate and are multidimensional - Corrected Proof

2009-11-02

Abstract: Objective: To examine the relationships among seven frailty domains: nutrition, physical activity, mobility, strength, energy, cognition, and mood, using data from three studies.Study Design and Setting: Data from three studies were separately analyzed using multiple correspondence analysis (MCA). The graphical output of MCA was used to assess (1) if the presence of deficits in the frailty domains separate from the absence of deficits on the graph, (2) the dimensionality of the domains, (3) the clustering of domains within each dimension, and (4) their relationship with age, sex, and disability. Results were compared across the studies.Results: In two studies, presence of deficits for all domains separated from absence of deficits. In the third study, there was separation in all domains except cognition. Three main dimensions were retained in each study; however, assigned dimensionality of domains differed. The clustering of mobility with energy and/or strength was consistent across studies. Deficits were associated with older age, female sex, and disability.Conclusion: Our results suggest that frailty is a multidimensional concept for which the relationships among domains differ according to the population characteristics. These domains, with the possible exception of cognition, appear to aggregate together and share a common underlying construct.

Common problems related to the use of number needed to treat - Corrected Proof

Andreas Stang, Charles Poole, Ralf Bender — 2009-11-02

Abstract: Objective: To illustrate basic issues that have to be taken into account when study results are presented by means of the number needed to treat (NNT).Study Design and Setting: This article presents an overview of common problems related to the NNT with corresponding explanations.Results: Without stating the direction of the effect, the alternative treatment, the treatment period, and the follow-up period, information in terms of NNTs is uninterpretable. The naive use of person-time data for the calculation of NNTs is frequently inappropriate. Rounding NNTs to the next upward integer may obscure differences among therapies.Conclusions: The basic information about which treatments are compared, the treatment period, the follow-up period, and the direction of the effect should be given when study results are presented in terms of NNTs. Adequate methods should be used for point and interval estimation of NNTs. Unnecessary rounding of NNTs should be avoided. In more complicated situations of confounding or varying follow-up times, the use of more sophisticated methods is required with increasing potential for misinterpretation.

Challenges in the validation of triage systems at emergency departments - Corrected Proof

Henriëtte A. Moll — 2009-10-30

Abstract: Objectives: Triage systems, developed by consensus of experts and based on decision rules, are typically not validated. The objective is to discuss the challenges to evaluate the reliability and validity of triage systems.Study Design and Setting: Theoretical–conceptual approach to validate triage systems.Results: The consensus-based triage systems have to be applied to a broad population with a variety of signs and symptoms. For the individual patient-specific decision, rules are used and the outcome measure is, typically, one of five prognosis-specific urgency categories. In contrast, prediction rules in diagnostic research are developed for a narrow specific subpopulation and based on a combination of parameters to predict presence of a specific diagnosis. Reliability is based on case scenario and simultaneous triage studies. The first step in triage validation is to decide on the best proxy for prognosis, “the reference standard” for the urgency classification. The next step is modification of the triage decision rules, including a multivariate approach. The final step is the validation in different settings and to evaluate the impact in clinical practice.Conclusion: Triage should be viewed as diagnostic research and would benefit if it would use the available methodology in diagnostic research.

A questionnaire found disease-specific WORC index is not more responsive than SPADI and OSS in rotator cuff disease - Corrected Proof

2009-10-16

Abstract: Objectives: To compare responsiveness and minimal clinically important change (MCIC) for the disease-specific Western Ontario Rotator Cuff index (WORC) and the two region-specific questionnaires Shoulder Pain and Disability Index (SPADI) and Oxford Shoulder Scale (OSS) in patients with rotator cuff disease receiving corticosteroid injection therapy.Study Design and Setting: One hundred twenty-one patients with rotator cuff disease. Western Ontario Rotator Cuff index, SPADI, and OSS were administered before treatment and at 2 and 6 weeks after corticosteroid injection. Responsiveness was compared between questionnaires using the standardized response mean (SRM), area under the receiver operating characteristic curve, and reliable change proportion (RCP) statistics. Minimal clinically important change estimates were reported.Results: The differences between questionnaires were small and not consistent across the different responsiveness indices. Shoulder Pain and Disability Index was significantly more responsive than OSS measured by SRM and RCP at 2 and 6 weeks. Western Ontario Rotator Cuff index was significantly more responsive than OSS in RCP and area under receiver operating characteristic curve at 6 weeks. Shoulder Pain and Disability Index was significantly more responsive than WORC measured by RCP at 2 weeks. Minimal clinically important change was estimated to 5, 275, and 20 points for OSS, WORC, and SPADI, respectively.Conclusions: All questionnaires are suitable for measuring change in patients with rotator cuff disease. Disease-specific WORC index is not more responsive than the region-specific SPADI and OSS in rotator cuff disease.

Short-form Zarit Caregiver Burden Interviews were valid in advanced conditions - Corrected Proof

Irene J. Higginson, Wei Gao, Diana Jackson, Joanna Murray, Richard Harding — 2009-10-16

Abstract: Objectives: To assess six short-form versions of Zarit Burden Interview (ZBI-12, ZBI-8, ZBI-7, ZBI-6, ZBI-4, and ZBI-1) among three caregiving populations.Study Design and Setting: Secondary analysis of carers' surveys in advanced cancer (n=105), dementia (n=131), and acquired brain injury (n=215). All completed demographic information and the ZBI-22 were used. Validity was assessed by Spearman correlations and internal consistency using Cronbach's alpha. Overall discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC).Results: All short-form versions, except the ZBI-1 in advanced cancer (rho=0.63), displayed good correlations (rho=0.74–0.97) with the ZBI-22. Cronbach's alphas suggested high internal consistency (range: 0.69–0.89) even for the ZBI-4. Discriminative ability was good for all short forms (AUC range: 0.90–0.99); the best AUC was for ZBI-12 (0.99; 95% confidence interval [CI]: 0.98–0.99) and the second best for ZBI-7 (0.98; 95% CI: 0.96–0.98) and ZBI-6 (0.98; 95% CI: 0.97–0.99).Conclusions: All six short-form ZBI have very good validity, internal consistency, and discriminative ability. ZBI-12 is endorsed as the best short-form version; ZBI-7 and ZBI-6 show almost equal properties and are suitable when a fewer-question version is needed. ZBI-4 and ZBI-1 are suitable for screening, but ZBI-1 may be less valid in cancer.

A first step to assess harm and benefit in clinical trials in one scale - Corrected Proof

2009-10-05

Abstract: Objective: To develop a simple system to assess benefit and harm of treatment on a single scale. Harm and benefit signals from trials need to be placed in the proper perspective to decide on the value of a treatment. Several systems have been developed for assessment, but few attempt to incorporate both benefit and risk in the same metric while retaining enough simplicity to aid patients and clinicians in their decision making.Study Design and Setting: We designed a very simple 3×3 table (Outcome Measures in Rheumatology [OMERACT] 3×3) that comprises three ranks for both beneficial and harm outcomes: for benefit, these are “none,” “substantial,” and “(near) remission”; for harm, these are “none,” “severe,” and “(near) death.” Patients are ranked both for benefit and harm and subsequently counted in a 3×3 table.Results: The system was feasible when applied to one trial dataset (patient-level information) and a meta-analysis. To become applicable as a tool, several issues need to be resolved in further development, especially the definitions and cutoffs for the ranks.Conclusion: A simple 3×3 table to rank both benefit and harm outcomes is feasible. For rheumatology this will be further developed in the context of the OMERACT initiative.

Older Australians' medication use: self-report by phone showed good agreement and accuracy compared with home visit - Corrected Proof

Sabrina Pit, Julie Byles — 2009-09-29

Abstract: Objective: To ascertain the accuracy of telephone-interview method for measuring older people's medication use (“self-report by phone”) by determining agreement between results from this method and from a home visit (“home inventory”).Study Design and Setting: An agreement study involving community-dwelling patients aged more than 65 years, selected from four general practices in the Hunter Region of Australia. Commonly used classes of drugs were selected for comparison.Results: Of 154 patients, 14 participants were ineligible, because they had hearing problems (9) or did not use any medicines (5). The response rate was 70% (98 of 140). The observed overall agreement and prevalence-adjusted and bias-adjusted kappa coefficients were very high for all prescribed drug categories, but lower for over-the-counter (OTC) and complementary medicines. Specificity of the self-report by phone compared with home inventory was consistently high across all drug classes. Sensitivity values were more than 89% for all drug classes but were lower for OTC and complementary medicines (74%) and paracetamol (78%). Similar patterns were found for negative predictive values. Positive predictive values were lower for drugs used on an as-needed basis.Conclusion: Measuring patient's medication use by telephone is an accurate and relatively inexpensive alternative to home-inventory methods, and has merit for use in future studies of older patients' drug use.

Research in rehabilitation medicine: Methodological challenges - Corrected Proof

Derick T. Wade, Rob J.E.M. Smeets, Jeanine A. Verbunt — 2009-09-29

Abstract: Objective: To provide an overview of methodological issues specifically related to the evaluation of rehabilitation interventions studies.Study design and setting: Narrative review covering studies evaluating interventions in rehabilitation medicine with methodological issues.Results: Four main methodological issues could be identified. First, the inclusion of patients. Patients should be selected based on having the problem being addressed by the intervention and not based on other criteria such as disease diagnosis. Second, the description of the intervention. Rehabilitation is a problem-solving process undertaken by one group of people (therapists) with another group (patient and family). The specific intervention being studied is only one of many that may affect outcome. Describing the whole package is a real challenge. Third, the control group. A control intervention has to raise equal expectations in patients and therapists. Expectation bias is a very probable influence on measured outcomes. Fourth, the definition of an appropriate outcome. In contrast to traditional biomedical research, rehabilitation research should have at least one “process” (proximate) or intervening variable measure and several distal primary outcome measures.

A probiotics trial on trial: the problem of timely detection of adverse advents in therapeutic trials - Corrected Proof

Raimond W.M. Giard — 2009-09-18

The outcome of a therapeutic trial may be frustrating. In a recent Dutch randomized, double-blind, placebo-controlled multicenter trial, the effects of probiotics were studied to investigate their potential to diminish infectious complications in patients with predicted severe acute pancreatitis . Desolately, the results of this study were quite contrary to expectations: there was no diminution of infectious complications, and furthermore, patients taking the probiotics had more than double the relative mortality risk. Finally, 33 of the 297 patients included in this trial died with an excess of 15 deaths occurring in the treatment group ().