The core epistemic responsibilities of universities: Results from a Delphi study.

Epistemic responsibilities (ERs) of universities concern equipping and empowering its researchers, educators and students to attain, produce, exchange and disseminate knowledge. ERs can potentially guide universities in improving education, research and in service to society. Building on earlier philosophical work, we applied empirical methods to identify core ERs of universities and their constituting elements. We used a three-round Delphi survey, alternating between closed questions to gain consensus, and open questions to let panelists motivate their answers. 46 panelists participated in our study. We reached consensus on six ERs: 1) to foster research integrity, 2) to stimulate the development of intellectual virtues, 3) to address the big questions of life, 4) to cultivate the diversity of the disciplinary fields, 5) to serve and engage with society at large, and 6) to cultivate and safeguard academic freedom. Together the six ERs contain 27 elements. Consensus rates ranged from 73%-100% for both the ERs and their elements. Participants' detailed responses led to substantial improvements in the accompanying descriptions of the ERs. Our findings can inform the debate about the roles and responsibilities of universities, and inform researchers and policy makers to emphasize epistemic tasks of universities.

COSMIN Risk of Bias tool to assess the quality of studies on reliability or measurement error of outcome measurement instruments: a Delphi study.

BACKGROUND: Scores on an outcome measurement instrument depend on the type and settings of the instrument used, how instructions are given to patients, how professionals administer and score the instrument, etc. The impact of all these sources of variation on scores can be assessed in studies on reliability and measurement error, if properly designed and analyzed. The aim of this study was to develop standards to assess the quality of studies on reliability and measurement error of clinician-reported outcome measurement instruments, performance-based outcome measurement instrument, and laboratory values. METHODS: We conducted a 3-round Delphi study involving 52 panelists. RESULTS: Consensus was reached on how a comprehensive research question can be deduced from the design of a reliability study to determine how the results of a study inform us about the quality of the outcome measurement instrument at issue. Consensus was reached on components of outcome measurement instruments, i.e. the potential sources of variation. Next, we reached consensus on standards on design requirements (n = 5), standards on preferred statistical methods for reliability (n = 3) and measurement error (n = 2), and their ratings on a four-point scale. There was one term for a component and one rating of one standard on which no consensus was reached, and therefore required a decision by the steering committee. CONCLUSION: We developed a tool that enables researchers with and without thorough knowledge on measurement properties to assess the quality of a study on reliability and measurement error of outcome measurement instruments.

Selective citation in scientific literature on the human health effects of bisphenol A.

INTRODUCTION: Bisphenol A is highly debated and studied in relation to a variety of health outcomes. This large variation in the literature makes BPA a topic that is prone to selective use of literature, in order to underpin one's own findings and opinion. Over time, selective use of literature, by means of citations, can lead to a skewed knowledge development and a biased scientific consensus. In this study, we assess which factors drive citation and whether this results in the overrepresentation of harmful health effects of BPA. METHODS: A citation network analysis was performed to test various determinants of citation. A systematic search identified all relevant publications on the human health effect of BPA. Data were extracted on potential determinants of selective citation, such as study outcome, study design, sample size, journal impact factor, authority of the author, self-citation, and funding source. We applied random effect logistic regression to assess whether these determinants influence the likelihood of citation. RESULTS: One hundred sixty-nine publications on BPA were identified, with 12,432 potential citation pathways of which 808 citations occurred. The network consisted of 63 cross-sectional studies, 34 cohort studies, 29 case-control studies, 35 narrative reviews, and 8 systematic reviews. Positive studies have a 1.5 times greater chance of being cited compared to negative studies. Additionally, the authority of the author and self-citation are consistently found to be positively associated with the likelihood of being cited. Overall, the network seems to be highly influenced by two highly cited publications, whereas 60 out of 169 publications received no citations. CONCLUSION: In the literature on BPA, citation is mostly driven by positive study outcome and author-related factors, such as high authority within the network. Interpreting the impact of these factors and the big influence of a few highly cited publications, it can be questioned to which extent the knowledge development in human literature on BPA is actually evidence-based.

COSMIN methodology for evaluating the content validity of patient-reported outcome measures: a Delphi study.

BACKGROUND: Content validity is the most important measurement property of a patient-reported outcome measure (PROM) and the most challenging to assess. Our aims were to: (1) develop standards for evaluating the quality of PROM development; (2) update the original COSMIN standards for assessing the quality of content validity studies of PROMs; (3) develop criteria for what constitutes good content validity of PROMs, and (4) develop a rating system for summarizing the evidence on a PROM's content validity and grading the quality of the evidence in systematic reviews of PROMs. METHODS: An online 4-round Delphi study was performed among 159 experts from 21 countries. Panelists rated the degree to which they (dis)agreed to proposed standards, criteria, and rating issues on 5-point rating scales ('strongly disagree' to 'strongly agree'), and provided arguments for their ratings. RESULTS: Discussion focused on sample size requirements, recording and field notes, transcribing cognitive interviews, and data coding. After four rounds, the required 67% consensus was reached on all standards, criteria, and rating issues. After pilot-testing, the steering committee made some final changes. Ten criteria for good content validity were defined regarding item relevance, appropriateness of response options and recall period, comprehensiveness, and comprehensibility of the PROM. DISCUSSION: The consensus-based COSMIN methodology for content validity is more detailed, standardized, and transparent than earlier published guidelines, including the previous COSMIN standards. This methodology can contribute to the selection and use of high-quality PROMs in research and clinical practice.

COSMIN guideline for systematic reviews of patient-reported outcome measures.

PURPOSE: Systematic reviews of patient-reported outcome measures (PROMs) differ from reviews of interventions and diagnostic test accuracy studies and are complex. In fact, conducting a review of one or more PROMs comprises of multiple reviews (i.e., one review for each measurement property of each PROM). In the absence of guidance specifically designed for reviews on measurement properties, our aim was to develop a guideline for conducting systematic reviews of PROMs. METHODS: Based on literature reviews and expert opinions, and in concordance with existing guidelines, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) steering committee developed a guideline for systematic reviews of PROMs. RESULTS: A consecutive ten-step procedure for conducting a systematic review of PROMs is proposed. Steps 1-4 concern preparing and performing the literature search, and selecting relevant studies. Steps 5-8 concern the evaluation of the quality of the eligible studies, the measurement properties, and the interpretability and feasibility aspects. Steps 9 and 10 concern formulating recommendations and reporting the systematic review. CONCLUSIONS: The COSMIN guideline for systematic reviews of PROMs includes methodology to combine the methodological quality of studies on measurement properties with the quality of the PROM itself (i.e., its measurement properties). This enables reviewers to draw transparent conclusions and making evidence-based recommendations on the quality of PROMs, and supports the evidence-based selection of PROMs for use in research and in clinical practice.

COSMIN Risk of Bias checklist for systematic reviews of Patient-Reported Outcome Measures.

PURPOSE: The original COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was developed to assess the methodological quality of single studies on measurement properties of Patient-Reported Outcome Measures (PROMs). Now it is our aim to adapt the COSMIN checklist and its four-point rating system into a version exclusively for use in systematic reviews of PROMs, aiming to assess risk of bias of studies on measurement properties. METHODS: For each standard (i.e., a design requirement or preferred statistical method), it was discussed within the COSMIN steering committee if and how it should be adapted. The adapted checklist was pilot-tested to strengthen content validity in a systematic review on the quality of PROMs for patients with hand osteoarthritis. RESULTS: Most important changes were the reordering of the measurement properties to be assessed in a systematic review of PROMs; the deletion of standards that concerned reporting issues and standards that not necessarily lead to biased results; the integration of standards on general requirements for studies on item response theory with standards for specific measurement properties; the recommendation to the review team to specify hypotheses for construct validity and responsiveness in advance, and subsequently the removal of the standards about formulating hypotheses; and the change in the labels of the four-point rating system. CONCLUSIONS: The COSMIN Risk of Bias checklist was developed exclusively for use in systematic reviews of PROMs to distinguish this application from other purposes of assessing the methodological quality of studies on measurement properties, such as guidance for designing or reporting a study on the measurement properties.

[Non-publication is common among phase 1, single-center, not prospectively registered, or early terminated clinical drug trials]. / Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?

The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95% confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of follow-up, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58%) were published as peer-reviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60% published; adjusted OR 2.6, 95% CI 1.1-5.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.7-10.0), and trials not belonging to phase 1-4 (60% published; adjusted OR 3.2, 95% CI 1.5 to 6.5) compared to phase 1 trials (35% published); trials with a company or investigator as applicant (63% published) compared to trials with a Contract Research Organization (CRO) as applicant (50% published; adjusted OR 1.7; 95% CI 1.1-2.8); and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.1-4.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.0-4.0) compared to single-center trials (45% published). Trials that were not prospectively registered (48% published) had a lower likelihood of publication compared to prospectively registered trials (75% published; adjusted OR 0.5, 95% CI 0.3-0.8), as well as trials that were terminated early (33% published) compared to trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.1-0.3). The non-publication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, single-center, not prospectively registered, and early terminated trials.

How do scientists perceive the current publication culture? A qualitative focus group interview study among Dutch biomedical researchers.

OBJECTIVE: To investigate the biomedical scientist's perception of the prevailing publication culture. DESIGN: Qualitative focus group interview study. SETTING: Four university medical centres in the Netherlands. PARTICIPANTS: Three randomly selected groups of biomedical scientists (PhD, postdoctoral staff members and full professors). MAIN OUTCOME MEASURES: Main themes for discussion were selected by participants. RESULTS: Frequently perceived detrimental effects of contemporary publication culture were the strong focus on citation measures (like the Journal Impact Factor and the H-index), gift and ghost authorships and the order of authors, the peer review process, competition, the funding system and publication bias. These themes were generally associated with detrimental and undesirable effects on publication practices and on the validity of reported results. Furthermore, senior scientists tended to display a more cynical perception of the publication culture than their junior colleagues. However, even among the PhD students and the postdoctoral fellows, the sentiment was quite negative. Positive perceptions of specific features of contemporary scientific and publication culture were rare. CONCLUSIONS: Our findings suggest that the current publication culture leads to negative sentiments, counterproductive stress levels and, most importantly, to questionable research practices among junior and senior biomedical scientists.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Therapeutic ultrasound for acute ankle sprains.

BACKGROUND: Ultrasound is used in the treatment of a wide variety of musculoskeletal disorders, which include acute ankle sprains. AIM: To evaluate the effects of ultrasound therapy in the treatment of acute ankle sprains. METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE until September 2010, CINAHL (until 2004), and PEDro (accessed 01/06/09). (Quasi)-randomised trials were included if the following conditions were met: at least one study group was treated with therapeutic ultrasound; participants had acute lateral ankle sprains; and outcome measures included general improvement, pain, swelling, functional disability, or range of motion. Risk ratios and risk differences with 95% confidence intervals were calculated for dichotomous outcomes and mean differences with 95% confidence intervals for continuous outcome measures. Limited pooling of data was undertaken where there was clinical homogeneity in terms of participants, treatments, outcomes, and follow-up time points. RESULTS: Six trials were included, involving 606 participants. Five trials included comparisons of ultrasound therapy with sham ultrasound; and three trials included single comparisons of ultrasound with three other treatments. None of the five placebo-controlled trials (sham ultrasound) demonstrated differences between true and sham ultrasound therapy for any outcome measure at one to four weeks of follow-up. The pooled risk ratio for general improvement at one week was 1.04 (random-effects model, 95% confidence interval 0.92 to 1.17) for active versus sham ultrasound. The differences between intervention groups were generally small, between 0% and 6%, for most dichotomous outcomes. CONCLUSION: The evidence from the five small placebo-controlled trials included in this review does not support the use of ultrasound in the treatment of acute ankle sprains. The potential treatment effects of ultrasound appear to be generally small and probably of limited clinical importance, especially in the context of the short-term recovery period in most people with these injuries. However, the available evidence is insufficient to rule out the possibility that there is an optimal dosage schedule for ultrasound therapy that may be of benefit.

Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective.

SUMMARY: This study evaluated the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of falling. The intervention and usual care groups did not differ in fall risk or costs. The multifactorial approach was not cost-effective compared to usual care in this group. INTRODUCTION: International guidelines recommend multifactorial evaluation and tailored treatment of risk factors to reduce falling in older persons. The cost-effectiveness may be enhanced in high-risk persons. Our study evaluates the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of recurrent falling. METHODS: An economic evaluation was conducted alongside a randomised controlled trial. Participants (≥65 years) with a high risk of recurrent falling were randomised into an intervention (n = 106) and usual care group (n = 111). The intervention consisted of multifactorial assessment and treatment of fall risk factors. Clinical outcomes were proportions of fallers and utility during 1 year. Costs were measured using questionnaires at 3, 6 and 12 months after baseline and valued using cost prices, if available, and guideline prices. Differences in costs and cost-effectiveness were analysed using bootstrapping. Cost-effectiveness planes and acceptability curves were presented. RESULTS: During 1 year, 52% and 56% of intervention and usual care participants reported at least one fall, respectively. The clinical outcome measures did not differ between the two groups. The mean costs were Euro 7,740 (SD 9,129) in the intervention group and Euro 6,838 (SD 8,623) in the usual care group (mean difference Euro 902, bootstrapped 95% CI: -1,534 to 3,357). Cost-effectiveness planes and acceptability curves indicated that multifactorial evaluation and treatment of fall risk factors was not cost-effective compared with usual care. CONCLUSIONS: Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective compared to usual care.

Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk, but the magnitude of this risk is not known precisely. A study was undertaken to investigate the associations between RA and type 2 diabetes (DM2), a well-established cardiovascular risk factor, on the one hand, and cardiovascular disease (CVD) on the other. METHODS: The prevalence of CVD (coronary, cerebral and peripheral arterial disease) was determined in 353 randomly selected outpatients with RA (diagnosed between 1989 and 2001, aged 50-75 years; the CARRE study) and in participants of a population-based cohort study on diabetes and CVD (the Hoorn study). Patients with RA with normal fasting glucose levels from the CARRE study (RA, n = 294) were compared with individuals from the Hoorn study with normal glucose metabolism (non-diabetic, n = 258) and individuals with DM2 (DM2, n = 194). RESULTS: The prevalence of CVD was 5.0% (95% CI 2.3% to 7.7%) in the non-diabetic group, 12.4% (95% CI 7.5% to 17.3%) in the DM2 group and 12.9% (95% CI 8.8% to 17.0%) in those with RA. With non-diabetic individuals as the reference category, the age- and gender-adjusted prevalence odds ratio (OR) for CVD was 2.3 (95% CI 1.1 to 4.7) for individuals with DM2 and 3.1 (95% CI 1.6 to 6.1) for those with RA. There was an attenuation of the prevalences after adjustment for conventional cardiovascular risk factors (OR 2.0 (95% CI 0.9 to 4.5) and 2.7 (95% CI 1.2 to 5.9), respectively). CONCLUSIONS: The prevalence of CVD in RA is increased to an extent that is at least comparable to that of DM2. This should have implications for primary cardiovascular prevention strategies in RA.

Neuropeptide Y polymorphism significantly magnifies diabetes and cardiovascular disease risk in obesity: the Hoorn Study.

The leucine7 to proline7 (Leu7Pro) polymorphism in preproneuropeptide Y (preproNPY) has been associated with accelerated atherosclerosis and type II diabetes, both of which are obesity-related diseases. The current study evaluated the impact of obesity on the disease risk linked to the Leu7Pro polymorphism of preproNPY in 393 elderly subjects. In 6 years follow-up, the polymorphism alone did not change the risk for abnormal glucose regulation, while obesity was associated with a significant 3-fold risk (odds ratio (OR) 2.95; 95% confidence interval (CI) 1.81-4.81, P<0.001) and the Leu7Pro polymorphism-obesity interaction, with a remarkable 12-fold risk (OR 12.33; 95% CI 1.18-128.35, P<0.05). The Leu7Pro polymorphism modified significantly the 10-year incidence of cardiovascular events, causing a 7.6-fold increase in the hazard ratio (HR 7.58; 95% CI 2.87-20.03, P<0.001) in the obese but not in the nonobese subjects. The results indicate that obesity may be a pivotal factor in multiplying the disease risk associated with the Leu7Pro polymorphism in preproNPY.

A study of the effects of acarbose on glucose metabolism in patients predisposed to developing diabetes: the Dutch acarbose intervention study in persons with impaired glucose tolerance (DAISI).

BACKGROUND: We hypothesized that acarbose would delay conversion from impaired glucose tolerance (IGT) to type 2 diabetes by alleviating postprandial hyperglycaemia. Our study's main objective was to investigate the effect of acarbose in IGT-persons on their 2-h plasma glucose level and beta-cell function. SUBJECTS AND METHODS: The study included a random sample of 45-70-year-old residents of Hoorn, Netherlands, with mean fasting plasma glucose < 7.8 mmol/L and mean 2-h plasma glucose of 8.6-11.1 mmol/L (measured by two successive oral glucose tolerance tests). After a qualification period, participants were randomized to acarbose treatment or placebo. Insulin secretion and insulin sensitivity were measured by hyperglycaemic clamp. After a 3-year treatment, analyses were performed of both the intention-to-treat and the per-protocol groups. RESULTS: Of the 12 093 residents who received postal invitations, 118 participants were randomized. The mean difference of the post-load plasma glucose after 3 years, was - 1.16 mmol/L (95% CI: - 2.03; - 0.17). The absolute risk reduction for diabetes was 6% (95% CI: - 9; 21). No effect was seen on insulin secretion and insulin sensitivity. CONCLUSIONS: In patients with IGT, treatment with acarbose was associated with beneficial effects on 2-h plasma glucose levels but not with improvement of beta-cell function.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus: The Hoorn Study.

OBJECTIVE: To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). RESEARCH DESIGN AND METHODS: Cross-sectional data from a population-based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score > or = 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels. RESULTS: The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P < 0.01), respectively. Depression was significantly more common in women with IGM [odds ratio (OR) = 3.60, 95% confidence interval (CI) = 1.57 to 8.28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non-significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms reduced the strength of these associations. CONCLUSIONS: Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could be intermediate factors.

Absence of an acute insulin response predicts onset of type 2 diabetes in a Caucasian population with impaired glucose tolerance.

CONTEXT: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. OBJECTIVES: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. DESIGN, SETTING, AND PARTICIPANTS: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. RESULTS: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60-12.67] for absence of first insulin peak, 1.58 (95% CI 0.60-4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65-4.88) for lowest vs. highest tertile of the disposition index. CONCLUSIONS: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.

Morbidity severity classifying routine consultations from English and Dutch general practice indicated physical health status.

OBJECTIVE: To investigate the construct validity of morbidity severity scales based on routine consultation data by studying their associations with sociodemographic factors and physical health. STUDY DESIGN AND SETTING: Study participants were 11,232 English adults aged 50 years and over and 9,664 Dutch adults aged 18 years and over, and their consulting morbidity data in a 12-month period were linked to their physical health data. Consulters with any of 115 morbidities classified on four ordinal scales of severity ("chronicity," "time course," "health care use," and "patient impact") were compared to all other consulters. RESULTS: As hypothesized, in both countries, morbidity severity was associated with older age, female gender, more deprivation (all comparisons P< or =0.05), and poor physical health (all trends P<0.001). The estimated strengths of association of poor physical health with the highest severity category expressed as odds ratios, for each of the four scales, were 5.4 for life-threatening on the "chronicity" scale, 1.8 for time course, 2.8 for high health care use, and 3.7 for high patient impact. CONCLUSIONS: Four scales of morbidity severity have been validated in English and Dutch settings, and they offer the potential to use simple routine consultation data as an indicator of physical health status in populations from general practice.

Deteriorating glucose tolerance status is associated with left ventricular dysfunction--the Hoorn Study.

BACKGROUND: Type 2 diabetes (DM2) is associated with a greater risk of heart failure. The mechanisms underlying this association remain controversial and include diabetes-associated hypertension and obesity, impaired small and large artery function, and a distinct metabolic cardiomyopathy related to hyperglycaemia/ hyperinsulinaemia. The proximate causes of heart failure are left ventricular (LV) systolic dysfunction (SDF) and diastolic dysfunction (DDF). We investigated, in a population-based cohort (n=746), the association between glucose tolerance status and SDF and DDF . METHODS AND RESULTS: The study population consisted of 274 individuals with normal glucose metabolism (NGM), 174 with impaired glucose metabolism (IGM) and 298 with DM2 (mean age 68.5 years). All participants underwent an LV echocardiogram. SDF was defined as ejection fraction <55%. DDF was determined by a sum score of peak A velocity (abnormal, >or =97 cm/s), the difference between Apv and Amv duration (> or =41 ms), and left atrial volume (> or =57 ml), where cut-off values were based upon the 90th percentile in NGM. In addition, we analysed the ratio of early to late diastolic filling (E/A ratio) on a continuous scale using linear regression analyses. The age- and sex-standardised prevalences in NGM, IGM and DM2 were 13, 14 and 30% for SDF , and 26, 36 and 47% for DDF (P trend for both <0.001). After adjustment for sex, age, hypertension, body mass index, prior cardiovascular disease and (micro) albuminuria, DM2 was significantly associated with both SDF (odds ratio (95% CI) 2.04 (1.24 to 3.36)) and DDF (2.42 (1.63 to 3.60)) (90th percentile definition). This was also true for the analyses with the E/A ratio on a continuous scale (regression coefficient b (95% CI) -0.05 (-0.09 to -0.01). After adjustment for sex, age, hypertension, body mass index, prior cardiovascular disease and (micro) albuminuria IGM was not significantly associated with SDF (odds ratio (95% CI) 1.04 (0.58 to 1.88)) or DDF (1.33 (0.86 to 2.06)) using the definition based upon the 90th percentile. However, IGM was significantly associated with DDF if the E/A ratio was analysed on a continuous scale (regression coefficient beta (95% CI) -0.05 (-0.10 to -0.01). Additional adjustment for brachial artery flow-mediated vasodilation or arterial stiffness, as measures of large artery function, did not materially alter the results. Hyperglycaemia and hyperinsulinaemia together explained approximately 30% of the association of DM2 with SDF and approximately 40% of that with DDF . CONCLUSION: DM2 is independently associated with a 2.0-fold greater risk of SDF and a 2.4-fold greater risk of DDF . IGM was not associated with SDF , and the association with DDF was limited to the E/A ratio. These observations may therefore explain the increased risk of systolic and diastolic heart failure in elderly individuals with DM2.

Surgical treatment options for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome is a common disorder for which several surgical treatment options are available. OBJECTIVES: To compare the efficacy of the various surgical techniques in relieving symptoms and promoting return to work or activities of daily living and to compare the occurrence of side-effects and complications in patients suffering from carpal tunnel syndrome. SEARCH STRATEGY: We updated the searches in 2006. We conducted computer-aided searches of the Cochrane Neuromuscular Disease Group Trials Register (searched in June 2006), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 2), MEDLINE (January 1966 to June 2006), EMBASE (January 1980 to June 2006) and also tracked references in bibliographies. SELECTION CRITERIA: Randomised controlled trials comparing various surgical techniques for the treatment of carpal tunnel syndrome. DATA COLLECTION AND ANALYSIS: Two review authors performed study selection, assessment of methodological quality and data extraction independently of each other. MAIN RESULTS: Thirty-three studies were included in the review of which 10 were newly identified in this update. The methodological quality of the trials ranged from fair to good; however, the use of allocation concealment was mentioned explicitly in only seven trials. Many studies failed to present the results in sufficient detail to enable statistical pooling. Pooling was also impeded by the vast variety of outcome measures that were applied in the various studies. None of the existing alternatives to standard open carpal tunnel release offered significantly better relief from symptoms in the short- or long-term. In three studies with a total of 294 participants, endoscopic carpal tunnel release resulted in earlier return to work or activities of daily living than open carpal tunnel release, with a weighted mean difference of -6 days (95% CI -9 to -3 days). AUTHORS' CONCLUSIONS: There is no strong evidence supporting the need for replacement of standard open carpal tunnel release by existing alternative surgical procedures for the treatment of carpal tunnel syndrome. The decision to apply endoscopic carpal tunnel release instead of open carpal tunnel release seems to be guided by the surgeon's and patient's preferences.