An empirical study of how the Dutch healthcare regulator first formulates the concept of trust and then puts it into practice.

BACKGROUND: Responsive regulation assumes that the parties being regulated are trustworthy and motivated by social responsibility. This assumes that regulation based upon trust will improve the regulated organization more effectively than other regulation models. The purpose of our qualitative study was to unravel the most important elements of trust in the inspectee which can support the inspector's work and to develop a model and a framework of trust that can be used by the inspectors to legitimize their trust in the inspectee. METHODS: We conducted an empirical study on trust regarding the regulation of care services to reveal how trust in the inspectee is conceptualized and assessed. Based on literature and empirical research, we synthesized the concept of trust into six elements, five regarding behavior, and a sixth looking at information about its context. We developed a practical framework for the concept to reduce the conceptual ambiguity, strengthen regulatory assessment, and support appropriate tailoring of the regulatory response. RESULTS: Six elements with respect to trust emerged from the data: showing integrity; transparency; ability to learn; accepting feedback; showing actual change in behavior; context information. These five behavioral elements, plus the context information were merged into a Framework of Trust and designed into an interactive PDF document. CONCLUSIONS: This study has sought to address a gap in the empirical knowledge regarding the assessment of trust in the inspectee. The results aim to inform and clarify the regulatory conceptualization and understanding of trust in the inspectee. Other inspectorates may learn from these results for their own practice and explore whether operational deployment of our Framework of Trust effects their assessment and enforcement strategies.

Endovascular revascularisation versus conservative management for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is the classic symptomatic form of peripheral arterial disease affecting an estimated 4.5% of the general population aged 40 years and older. Patients with IC experience limitations in their ambulatory function resulting in functional disability and impaired quality of life (QoL). Endovascular revascularisation has been proposed as an effective treatment for patients with IC and is increasingly performed. OBJECTIVES: The main objective of this systematic review is to summarise the (added) effects of endovascular revascularisation on functional performance and QoL in the management of IC. SEARCH METHODS: For this review the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). The CIS also searched trials registries for details of ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing endovascular revascularisation (± conservative therapy consisting of supervised exercise or pharmacotherapy) versus no therapy (except advice to exercise) or versus conservative therapy (i.e. supervised exercise or pharmacotherapy) for IC. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data, and assessed the methodological quality of studies. Given large variation in the intensity of treadmill protocols to assess walking distances and use of different instruments to assess QoL, we used standardised mean difference (SMD) as treatment effect for continuous outcome measures to allow standardisation of results and calculated the pooled SMD as treatment effect size in meta-analyses. We interpreted pooled SMDs using rules of thumb (< 0.40 = small, 0.40 to 0.70 = moderate, > 0.70 = large effect) according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated the pooled treatment effect size for dichotomous outcome measures as odds ratio (OR). MAIN RESULTS: We identified ten RCTs (1087 participants) assessing the value of endovascular revascularisation in the management of IC. These RCTs compared endovascular revascularisation versus no specific treatment for IC or conservative therapy or a combination therapy of endovascular revascularisation plus conservative therapy versus conservative therapy alone. In the included studies, conservative treatment consisted of supervised exercise or pharmacotherapy with cilostazol 100 mg twice daily. The quality of the evidence ranged from low to high and was downgraded mainly owing to substantial heterogeneity and small sample size.Comparing endovascular revascularisation versus no specific treatment for IC (except advice to exercise) showed a moderate effect on maximum walking distance (MWD) (SMD 0.70, 95% confidence interval (CI) 0.31 to 1.08; 3 studies; 125 participants; moderate-quality evidence) and a large effect on pain-free walking distance (PFWD) (SMD 1.29, 95% CI 0.90 to 1.68; 3 studies; 125 participants; moderate-quality evidence) in favour of endovascular revascularisation. Long-term follow-up in two studies (103 participants) showed no clear differences between groups for MWD (SMD 0.67, 95% CI -0.30 to 1.63; low-quality evidence) and PFWD (SMD 0.69, 95% CI -0.45 to 1.82; low-quality evidence). The number of secondary invasive interventions (OR 0.81, 95% CI 0.12 to 5.28; 2 studies; 118 participants; moderate-quality evidence) was also not different between groups. One study reported no differences in disease-specific QoL after two years.Data from five studies (n = 345) comparing endovascular revascularisation versus supervised exercise showed no clear differences between groups for MWD (SMD -0.42, 95% CI -0.87 to 0.04; moderate-quality evidence) and PFWD (SMD -0.05, 95% CI -0.38 to 0.29; moderate-quality evidence). Similarliy, long-term follow-up in three studies (184 participants) revealed no differences between groups for MWD (SMD -0.02, 95% CI -0.36 to 0.32; moderate-quality evidence) and PFWD (SMD 0.11, 95% CI -0.26 to 0.48; moderate-quality evidence). In addition, high-quality evidence showed no difference between groups in the number of secondary invasive interventions (OR 1.40, 95% CI 0.70 to 2.80; 4 studies; 395 participants) and in disease-specific QoL (SMD 0.18, 95% CI -0.04 to 0.41; 3 studies; 301 participants).Comparing endovascular revascularisation plus supervised exercise versus supervised exercise alone showed no clear differences between groups for MWD (SMD 0.26, 95% CI -0.13 to 0.64; 3 studies; 432 participants; moderate-quality evidence) and PFWD (SMD 0.33, 95% CI -0.26 to 0.93; 2 studies; 305 participants; moderate-quality evidence). Long-term follow-up in one study (106 participants) revealed a large effect on MWD (SMD 1.18, 95% CI 0.65 to 1.70; low-quality evidence) in favour of the combination therapy. Reports indicate that disease-specific QoL was comparable between groups (SMD 0.25, 95% CI -0.05 to 0.56; 2 studies; 330 participants; moderate-quality evidence) and that the number of secondary invasive interventions (OR 0.27, 95% CI 0.13 to 0.55; 3 studies; 457 participants; high-quality evidence) was lower following combination therapy.Two studies comparing endovascular revascularisation plus pharmacotherapy (cilostazol) versus pharmacotherapy alone provided data showing a small effect on MWD (SMD 0.38, 95% CI 0.08 to 0.68; 186 participants; high-quality evidence), a moderate effect on PFWD (SMD 0.63, 95% CI 0.33 to 0.94; 186 participants; high-quality evidence), and a moderate effect on disease-specific QoL (SMD 0.59, 95% CI 0.27 to 0.91; 170 participants; high-quality evidence) in favour of combination therapy. Long-term follow-up in one study (47 participants) revealed a moderate effect on MWD (SMD 0.72, 95% CI 0.09 to 1.36; P = 0.02) in favour of combination therapy and no clear differences in PFWD between groups (SMD 0.54, 95% CI -0.08 to 1.17; P = 0.09). The number of secondary invasive interventions was comparable between groups (OR 1.83, 95% CI 0.49 to 6.83; 199 participants; high-quality evidence). AUTHORS' CONCLUSIONS: In the management of patients with IC, endovascular revascularisation does not provide significant benefits compared with supervised exercise alone in terms of improvement in functional performance or QoL. Although the number of studies is small and clinical heterogeneity underlines the need for more homogenous and larger studies, evidence suggests that a synergetic effect may occur when endovascular revascularisation is combined with a conservative therapy of supervised exercise or pharmacotherapy with cilostazol: the combination therapy seems to result in greater improvements in functional performance and in QoL scores than are seen with conservative therapy alone.

Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

OBJECTIVES: To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. METHODS: Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. RESULTS: MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100% (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. CONCLUSIONS: Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). KEY POINTS: PROPELLER MRI does not match CT sensitivity to assess CF lung disease. PROPELLER MRI has lower sensitivity than CT to detect severe bronchiectasis. PROPELLER MRI has good to very good intra- and inter-observer variability. PROPELLER MRI can be used for short-term follow-up studies in CF.

Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication: A Randomized Clinical Trial.

IMPORTANCE: Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available. OBJECTIVE: To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle. INTERVENTIONS: A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106). MAIN OUTCOMES AND MEASURES: The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation]). RESULTS: Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions. CONCLUSIONS AND RELEVANCE: Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only. TRIAL REGISTRATION: Netherlands Trial Registry Identifier: NTR2249.

The role of imaging specialists as authors of systematic reviews on diagnostic and interventional imaging and its impact on scientific quality: report from the EuroAIM Evidence-based Radiology Working Group.

PURPOSE: To evaluate the inclusion of radiologists or nuclear medicine physicians (imaging specialists) as authors of systematic reviews (SRs) on imaging and imaging-guided diagnostic procedures and to determine the impact of imaging specialists' presence as authors on the overall quality of the reviews. MATERIALS AND METHODS: A MEDLINE and EMBASE search was performed for SRs of diagnostic and interventional image-guided procedures that were published from January 2001 to December 2010. SRs about procedures primarily performed by nonimaging specialists were excluded. The inclusion of imaging specialists among the SR authors and the frequency of publication in imaging journals were evaluated. The quality of a subset of 200 SRs (100 most recent SRs with imaging specialists as authors and 100 most recent SRs without imaging specialists as authors) was rated by using a 12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman, χ(2), and Mann-Whitney statistics were used. RESULTS: From among 3258 retrieved citations, 867 SRs were included in the study. Neuroimaging had the largest number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic performance, and 26% (228 of 867) of SRs were published in imaging journals. Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging specialists as authors were more often published in imaging journals than in nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median number of modified AMSTAR quality indicators was nine in SRs with imaging specialists as authors, while that in SRs without imaging specialists as authors was seven (P = .003). CONCLUSION: Only 38% (330 of 867) of SRs on radiology or nuclear medicine-related imaging published from January 2001 to December 2010 included imaging specialists as authors. However, the inclusion of imaging specialists as authors was associated with a significant increase in the scientific quality (as judged by using a modified AMSTAR scale) of the SR.

Modes of exercise training for intermittent claudication.

BACKGROUND: According to international guidelines and literature, all patients with intermittent claudication should receive an initial treatment of cardiovascular risk modification, lifestyle coaching, and supervised exercise therapy. In most studies, supervised exercise therapy consists of treadmill or track walking. However, alternative modes of exercise therapy have been described and yielded similar results to walking. Therefore, the following question remains: Which exercise mode gives the most beneficial results? PRIMARY OBJECTIVE: To assess the effects of different modes of supervised exercise therapy on the maximum walking distance (MWD) of patients with intermittent claudication. SECONDARY OBJECTIVES: To assess the effects of different modes of supervised exercise therapy on pain-free walking distance (PFWD) and health-related quality of life scores (HR-QoL) of patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Cochrane Peripheral Vascular Diseases Group Specialised Register (July 2013); CENTRAL (2013, Issue 6), in The Cochrane Lib rary; and clinical trials databases. The authors searched the MEDLINE (1946 to July 2013) and Embase (1973 to July 2013) databases and reviewed the reference lists of identified articles to detect other relevant citations. SELECTION CRITERIA: Randomised controlled trials of studies comparing alternative modes of exercise training or combinations of exercise modes with a control group of supervised walking exercise in patients with clinically determined intermittent claudication. The supervised walking programme needed to be supervised at least twice a week for a consecutive six weeks of training. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data, and assessed the risk of bias for each study. Because of different treadmill test protocols to assess the maximum or pain-free walking distance, we converted all distances or walking times to total metabolic equivalents (METs) using the American College of Sports Medicine (ACSM) walking equation. MAIN RESULTS: In this review, we included a total of five studies comparing supervised walking exercise and alternative modes of exercise. The alternative modes of exercise therapy included cycling, strength training, and upper-arm ergometry. The studies represented a sample size of 135 participants with a low risk of bias. Overall, there was no clear evidence of a difference between supervised walking exercise and alternative modes of exercise in maximum walking distance (8.15 METs, 95% confidence interval (CI) -2.63 to 18.94, P = 0.14, equivalent of an increase of 173 metres, 95% CI -56 to 401) on a treadmill with no incline and an average speed of 3.2 km/h, which is comparable with walking in daily life.Similarly, there was no clear evidence of a difference between supervised walking exercise and alternative modes of exercise in pain-free walking distance (6.42 METs, 95% CI -1.52 to 14.36, P = 0.11, equivalent of an increase of 136 metres, 95% CI -32 to 304). Sensitivity analysis did not alter the results significantly. Quality of life measures showed significant improvements in both groups; however, because of skewed data and the very small sample size of the studies, we did not perform a meta-analysis for health-related quality of life and functional impairment. AUTHORS' CONCLUSIONS: There was no clear evidence of differences between supervised walking exercise and alternative exercise modes in improving the maximum and pain-free walking distance of patients with intermittent claudication. More studies with larger sample sizes are needed to make meaningful comparisons between each alternative exercise mode and the current standard of supervised treadmill walking. The results indicate that alternative exercise modes may be useful when supervised walking exercise is not an option for the patient.

Can magnetic resonance imaging at 3.0-Tesla reliably detect patients with endometriosis? Initial results.

AIM: The aim of this study was to determine whether an optimized 3.0-Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis. MATERIAL AND METHODS: This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0-Tesla MRI, including a T2-weighted high-resolution fast spin echo sequence (spatial resolution=0.75 ×1.2 ×1.5 mm³) and a 3D T1-weighted high-resolution gradient echo sequence (spatial resolution=0.75 ×1.2 × 2.0 mm³). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient-level and region-level sensitivities and specificities and lesion-level sensitivities were calculated. RESULTS: Patient-level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient-level specificity for all stages was 100% (3/3). The region-level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul-the-sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa=1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul-the-sac). CONCLUSIONS: An optimized 3.0-Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis.

Efficacy of biological agents in juvenile idiopathic arthritis: a systematic review using indirect comparisons.

OBJECTIVE: Over the past decade, the availability of biological agents for the treatment of juvenile idiopathic arthritis (JIA) has increased substantially. Because direct head-to-head trials comparing these agents are lacking, we indirectly compared their efficacy. METHODS: In a systematic review, all available efficacy data from randomised controlled trials performed in JIA with inclusion of biological agents were retrieved. Indirect between-drug comparisons (based on Bucher's method) were conducted only if trials were comparable with regard to design and patients' characteristics related to treatment outcome. RESULTS: We identified 11 randomised controlled trials. On the basis of the equality of the trials, six trials were grouped into two networks of evidence. Network 1 included withdrawal trials which evaluated etanercept, adalimumab and abatacept in polyarticular course JIA. Indirect comparisons identified no significant differences in short-term efficacy. Network 2 indirectly compared trials with a parallel study design investigating anakinra, tocilizumab and canakinumab in systemic JIA; no differences in comparative efficacy were identified. Although the two networks were constructed on the basis of comparability, small differences in trial design and case mix still existed. CONCLUSIONS: Because of the small number of trials and the observed differences between trials, no definite conclusions could be drawn about the comparative effectiveness of the indirectly compared biological agents. Therefore, for now, the paediatric rheumatologist has to rely on observational data and safety, practical and financial arguments. Comparability of future trials needs to be improved, and head-to-head trials are required to decide on the best biological treatment for JIA.

Clinical examination versus magnetic resonance imaging in the pretreatment staging of cervical carcinoma: systematic review and meta-analysis.

OBJECTIVES: To review the literature on the diagnostic performance of clinical examination and magnetic resonance imaging (MRI) in detecting parametrial invasion and advanced stage disease (FIGO stage ≥ IIB) in patients with cervical carcinoma. METHODS: Reports of studies were searched using the MEDLINE, EMBASE and Cochrane databases. Two observers reported on data relevant for analysis and methodological quality using the QUADAS scoring system. Publication bias was analysed using Deeks funnel plots. Covariates were added to the model to study the influence on the summary results of the technical and methodological aspects of the clinical examination and MRI. RESULTS: In total, 3,254 patients were included. Partial verification bias was often encountered. Pooled sensitivity was 40 % (95 % CI 25-58) for the evaluation of parametrial invasion with clinical examination and 84 % (95 % CI 76-90) with MRI, 53 % (95 % CI 41-66) for the evaluation of advanced disease with clinical examination, and 79 % (95 % CI 64-89) with MRI. Pooled specificities were comparable between clinical examination and MRI. Different technical aspects of MRI influenced the summary results. CONCLUSIONS: MRI is significantly better than clinical examination in ruling out parametrial invasion and advanced disease in patients with cervical carcinoma. KEY POINTS: • MRI has a higher sensitivity than clinical examination for staging cervical carcinoma. • Clinical examination and MRI have comparably high specificity for staging cervical carcinoma. • Quality of clinical examination studies was lower than that of MRI studies. • The use of newer MRI techniques positively influences the summary results. • Anaesthesia during clinical examination positively influences the summary results.

Preoperative breast MRI can reduce the rate of tumor-positive resection margins and reoperations in patients undergoing breast-conserving surgery.

OBJECTIVE: In breast cancer patients eligible for breast-conserving surgery, we evaluated whether the information provided by preoperative MRI of the breast would result in fewer tumor-positive resection margins and fewer reoperations. SUBJECTS AND METHODS: The study group consisted of 123 consecutive patients diagnosed with either breast cancer or ductal carcinoma in situ eligible for breast-conserving surgery between April 2007 and July 2010. For these patients, a first plan for breast-conserving surgery was made on the basis of clinical examination and conventional imaging. The final surgical plan was made with knowledge of the preoperative breast MRI. The rates of tumor-positive resection margins and reoperations were compared with those of a historical control group consisting of 119 patients who underwent 123 breast-conserving procedures between January 2005 and December 2006. The percentage of change in the surgical plan was recorded. RESULTS: Preoperative breast MRI changed the surgical plan to more extensive surgery in 42 patients (34.1%), mainly to mastectomy (29 patients, 23.6%). Ninety-four patients underwent 95 breast-conserving procedures. Significantly fewer patients had tumor-positive resection margins than in the control group (15.8%, 15/95 versus 29.3%, 36/123; p < 0.01). Patients in the study group underwent significantly fewer reoperations compared with the historical control group (18.9%, 18/95 vs 37.4%, 46/123; p < 0.01). CONCLUSION: Preoperative breast MRI can substantially decrease the rate of tumor-positive resection margins and reoperations in breast cancer patients eligible for breast-conserving surgery.

Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.

BACKGROUND: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. METHODS AND FINDINGS: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. CONCLUSIONS: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.

Methods for calculating sensitivity and specificity of clustered data: a tutorial.

UNLABELLED: The performance of a diagnostic test is often expressed in terms of sensitivity and specificity compared with the reference standard. Calculations of sensitivity and specificity commonly involve multiple observations per patient, which implies that the data are clustered. Whether analysis of sensitivity and specificity per patient or using multiple observations per patient is preferable depends on the clinical context and consequences. The purpose of this article was to discuss and illustrate the most common statistical methods that calculate sensitivity and specificity of clustered data, adjusting for the possible correlation between observations within each patient. This tutorial presents and illustrates the following methods: (a) analysis at different levels ignoring correlation, (b) variance adjustment, (c) logistic random-effects models, and (d) generalized estimating equations. The choice of method and the level of reporting should correspond with the clinical decision problem. If multiple observations per patient are relevant to the clinical decision problem, the potential correlation between observations should be explored and taken into account in the statistical analysis. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120509/-/DC1.

Supervised walking therapy in patients with intermittent claudication.

OBJECTIVE: Exercise therapy is a common intervention for the management of intermittent claudication (IC). However, considerable uncertainty remains about the effect of different exercise components such as intensity, duration, or content of the exercise programs. The aim of this study was to assess the effectiveness of supervised walking therapy (SWT) as treatment in patients with IC and to update and identify the most important exercise components resulting in an optimal training protocol for patients with IC. METHODS: A systematic literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases was performed. Randomized controlled trials (RCTs) published between January 1966 and February 2012 were included if they evaluated the effectiveness of SWT. Predefined exercise components were extracted, including treadmill use during training, claudication pain end point used during walking, length of the SWT program, and total training volume. A meta-analysis and meta-regression was performed to evaluate the weighted mean difference in maximum walking distance (MWD) and pain-free walking distance (PFWD) between SWT and noninterventional observation. RESULTS: Twenty-five RCTs (1054 patients) comparing SWT vs noninterventional observation showed a weighted mean difference of 180 meters (95% confidence interval, 130-230 meters) in MWD and 128 meters (95% confidence interval, 92-165 meters) in PFWD, both in favor of the SWT group. In multivariable meta-regression analysis, none of the predefined exercise components were independently associated with significant improvements in MWD or PFWD. CONCLUSIONS: SWT is effective in improving MWD and PFWD in patients with IC. However, pooled results from the RCTs did not identify any of the exercise components including intensity, duration, or content of the program as being independently associated with improvements in MWD or PFWD.

Systematic review of guidelines on abdominal aortic aneurysm screening.

OBJECTIVE: Usually, physicians base their practice on guidelines, but recommendations on the same topic may vary across guidelines. Given the uncertainties regarding abdominal aortic aneurysm (AAA) screening, physicians should be able to identify systematically and transparently developed recommendations. We performed a systematic review of AAA screening guidelines to assist physicians in their choice of recommendations. METHODS: Guidelines in English published between January 1, 2003 and February 26, 2010 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on AAA screening were included. Three reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Two independent reviewers performed extraction of recommendations. RESULTS: Of 2415 titles identified, seven guidelines were included in this review. Three guidelines were less rigorously developed based on AGREE scores below 40%. All seven guidelines contained a recommendation for one-time screening of elderly men by ultrasonography to select AAAs ≥ 5.5 cm for elective surgical repair. Four guidelines, of which three were less rigorously developed, contained disparate recommendations on screening of women and middle-aged men at elevated risk. There was no agreement on the management of smaller AAAs. CONCLUSIONS: Consensus exists across guidelines on one-time screening of elderly men to detect and treat AAAs ≥ 5.5 cm. For other target groups and management of small AAAs, prediction models and cost-effectiveness analyses are needed to provide guidance.

Long-term effects of structured home-based exercise program on functional capacity and quality of life in patients with intermittent claudication.

OBJECTIVES: To evaluate effects of a structured home-based exercise program on functional capacity and quality of life (QoL) in patients with intermittent claudication (IC) after 1-year follow-up, and to compare these results with those from a concurrent control group who received supervised exercise training (SET). DESIGN: Comparative longitudinal cohort study. SETTING: Referral center. PARTICIPANTS: Patients (N=142) with IC. INTERVENTIONS: Structured home-based exercise training or SET. MAIN OUTCOME MEASURES: The maximum (pain-free) walking distance and the ankle-brachial index (ABI) (at rest and postexercise) were measured at baseline and after 6 and 12 months' follow-up. Additionally, QoL was evaluated using a self-administered questionnaire consisting of the Euroqol-5D (scale 0-1), rating scale (scale 0-100), Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; scale 0-100), and the Vascular Quality of Life Questionnaire (VascuQol; scale 1-7). Comparison of the groups was performed with adjustment for the nonrandomized setting using propensity scoring. RESULTS: One hundred forty-two patients with IC started the structured home-based exercise program, of whom 95 (67%) completed 12 months' follow-up. The mean relative improvement compared with baseline was statistically significant after 12 months' follow-up for the maximum and pain-free walking distance (342%, 95% confidence interval [CI], 169-516; P<.01 and 338%, 95% CI, 42-635; P=.03, respectively) and for the ABI postexercise (mean change, .06; 95% CI, .01-.10; P=.02). For the QoL outcomes, the improvement compared with baseline was statistically significant after 12 months for the VascuQol (mean change, .42; 95% CI, .20-.65; P<.01) and for the SF-36 physical functioning (mean change, 5.17; 95% CI, .77-9.56; P=.02). Compared with the structured home-based exercise program, patients in the control group showed significantly better results in the mean relative improvement of maximum and pain-free walking distance and change in the ABI at rest after 12 months' follow-up. CONCLUSIONS: Structured home-based exercise training is effective in improving both functional capacity and QoL in patients with IC and may be considered as a feasible and valuable alternative toSET, since supervised exercise programs are not often available.

Value of information analyses of economic randomized controlled trials: the treatment of intermittent claudication.

OBJECTIVE: The aim of this study is to design the optimal study comparing endovascular revascularization and supervised exercise training for patients with intermittent claudication and to demonstrate value of information (VOI) analysis of patient-level data from an economic randomized controlled trial to guide future research. METHODS: We applied a net benefit framework to patient-level data on costs and quality-of-life of a previous randomized controlled trial. VOI analyses were performed using Monte Carlo simulation. We estimated the total expected value of perfect information (total EVPI), the total expected value of sample information (total EVSI), the partial expected value of perfect information (partial EVPI), and the partial expected value of sample information (partial EVSI). These VOI analyses identified the key parameters and the optimal sample size of future study designs. Sensitivity analyses were performed to explore the robustness of our assumptions about the population to benefit, the willingness-to-pay threshold, and the study costs. The VOI analyses are demonstrated in statistical software (R) and a spreadsheet (Excel) allowing other investigators to apply VOI analysis to their patient-level data. RESULTS: The optimal study design for the treatment of intermittent claudication involves a randomized controlled trial collecting data on the quality-adjusted life expectancy and additional admission costs for 525 patients per treatment arm. The optimal sample size remained between 400 and 600 patients for a willingness-to-pay threshold between euro30,000 and euro100,000/quality-adjusted life-years, for even extreme assumptions about the study costs, and for a range of 3 to 7 years that future patients will benefit from the results of the proposed study. CONCLUSIONS: 1) The optimal study for patients with intermittent claudication collects data on two key parameters for 525 patients per trial arm; and 2) we have shown that value of information analysis provides an explicit framework to determine the optimal sample size and identify key parameters for the design of future clinical trials.

Intermittent claudication: clinical effectiveness of endovascular revascularization versus supervised hospital-based exercise training--randomized controlled trial.

PURPOSE: To compare clinical success, functional capacity, and quality of life during 12 months after revascularization or supervised exercise training in patients with intermittent claudication. MATERIALS AND METHODS: This study had institutional review board approval, and all patients gave written informed consent. Between September 2002 and September 2005, 151 consecutive patients who presented with symptoms of intermittent claudication were randomly assigned to undergo either endovascular revascularization (angioplasty-first approach) (n = 76) or hospital-based supervised exercise (n = 75). The outcome measures were clinical success, functional capacity, and quality of life after 6 and 12 months. Clinical success was defined as improvement in at least one category in the Rutherford scale above the pretreatment level. Significance of differences between the groups was assessed with the unpaired t test, chi(2) test, or Mann-Whitney U test. To adjust outcomes for imbalances of baseline values, multivariable regression analysis was performed. RESULTS: Immediately after the start of treatment, patients who underwent revascularization improved more than patients who performed exercise in terms of clinical success (adjusted odds ratio [OR], 39; 99% confidence interval [CI]: 11, 131; P < .001), but this advantage was lost after 6 (adjusted OR, 0.9; 99% CI: 0.3, 2.3; P = .70) and 12 (adjusted OR, 1.1; 99% CI: 0.5, 2.8; P = .73) months. After revascularization, fewer patients showed signs of ipsilateral symptoms at 6 months compared with patients in the exercise group (adjusted OR, 0.4; 99% CI: 0.2, 0.9; P < .001), but no significant differences were demonstrated at 12 months. After both treatments, functional capacity and quality of life scores increased after 6 and 12 months, but no significant differences between the groups were demonstrated. CONCLUSION: After 6 and 12 months, patients with intermittent claudication benefited equally from either endovascular revascularization or supervised exercise. Improvement was, however, more immediate after revascularization.

Invasive treatment of claudication is indicated for patients unable to adequately ambulate during cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is of proven benefit for patients with coronary artery disease. Patients who successfully complete CR have a statistically significant reduction in the risk of fatal myocardial infarction (MI) and all-cause mortality. Peripheral arterial disease (PAD) is common in patients with coronary artery disease. OBJECTIVES: We investigated whether PAD prevents the successful completion of CR and cardiac risk reduction and whether invasive treatment of claudicant patients who cannot walk sufficiently to successfully complete CR is indicated. METHODS: The records of 230 consecutive CR patients were reviewed for attendance, target heart rate, and Walking Impairment Questionnaire (WIQ) values to compare PAD among successes and failures. Failure of CR was defined as inability to walk sufficiently to achieve target heart rate. Markov decision analysis using published data for endovascular and open intervention for claudication was used to compare outcomes of treatment strategies in which PAD is untreated (current standard), PAD is treated only if it interfered with CR, and treatment of PAD in all patients before initiating CR. RESULTS: Of 230 patients, 126 had complete records for analysis. Ankle-brachial indices (ABIs) were documented for 39 patients. Overall, 40% of patients failed CR. Failure was significantly more common in patients with claudication (76%) than in those without (26%; odds ratio [OR], 8.9; 95% confidence interval [CI], 3.7-21.7; P < .001). The presence of PAD, determined by the WIQ walking distance score, was significantly higher in the failure group (34%) vs the success group (17%; OR, 2.5; 95% CI, 1.1-6.0; P = .03). The presence of PAD, determined by ABI, was higher in the failure group (39%) vs the success group (14%; OR, 3.8; 95% CI, 0.8-17.9; P = .08). Logistic regression analysis when CR failure was adjusted for age and gender was significantly associated with presence of PAD based on WIQ walking distance score (OR, 2.8; 95% CI 1.1-7.1; P = .03). A strategy of invasive therapy only if PAD interfered with the successful completion of CR would save an additional 54 lives per 10,000 patients compared with no intervention. CONCLUSIONS: PAD is a significant cause of CR failure, preventing patients from successfully completing the program and achieving a reduction in risk of fatal cardiac events. Invasive treatment of PAD in patients who fail CR is indicated, with an expected lifesaving outcome.

Reference value of transcutaneous oxygen measurement in diabetic patients compared with nondiabetic patients.

PURPOSE: This study evaluated the values of transcutaneous oxygen tension (TcPo(2)) measurement in diabetic patients compared with nondiabetic patients and assessed its reproducibility. METHODS: In 60 diabetic patients (type 1 and type 2 diabetes mellitus) without signs of peripheral arterial disease or neuropathy, we measured TcPo(2) at the chest and foot and compared these measurements with 60 age- and sex-matched nondiabetic patients in a cross-sectional fashion. The reproducibility of TcPo(2) in terms of interobserver variability was also assessed. RESULTS: Diabetic patients had a mean +/- SD TcPo(2) value at the foot of 50.02 +/- 8.92 mm Hg, which was significantly lower compared with 56.04 +/- 8.80 mm Hg in nondiabetic patients (P < .001). At the chest wall, values for TcPo(2) were 51.77 +/- 11.15 mm Hg, and 58.22 +/- 12.47 mm Hg for diabetic patients and nondiabetic patients, respectively (P = .003). Regression analysis showed that TcPo(2)was significantly associated with diabetes mellitus (coefficient = -0.258; P = .004), and with having a first-degree relative with diabetes mellitus (coefficient = -0.265; P = .003). Furthermore, the interobserver variability showed a substantial correlation for both measurements at the chest (P < .001; r = 0.654; intraclass correlation coefficient [ICC] = 0.79) and at the dorsum of the foot (P < .001; r = 0.426; ICC = 0.60). CONCLUSION: Diabetic patients without signs of peripheral disease or neuropathy had significantly lower TcPo(2) values compared with age- and sex-matched nondiabetic patients. The influence of the examiner on the variance in TcPo(2) measurements was relatively small. We advocate the use of TcPo(2) measurement in diabetic patients to detect subclinical microvascular impairment as an additional tool to assess peripheral vascular disease.

Cost-effectiveness of endovascular revascularization compared to supervised hospital-based exercise training in patients with intermittent claudication: a randomized controlled trial.

BACKGROUND: The optimal first-line treatment for intermittent claudication is currently unclear. OBJECTIVE: To compare the cost-effectiveness of endovascular revascularization vs supervised hospital-based exercise in patients with intermittent claudication during a 12-month follow-up period. DESIGN: Randomized controlled trial with patient recruitment between September 2002-September 2006 and a 12-month follow-up per patient. SETTING: A large community hospital. PARTICIPANTS: Patients with symptoms of intermittent claudication due to an iliac or femoro-popliteal arterial lesion (293) who fulfilled the inclusion criteria (151) were recruited. Excluded were, for example, patients with lesions unsuitable for revascularization (iliac or femoropopliteal TASC-type D and some TASC type-B/C. INTERVENTION: Participants were randomly assigned to endovascular revascularization (76 patients) or supervised hospital-based exercise (75 patients). MEASUREMENTS: Mean improvement of health-related quality-of-life and functional capacity over a 12-month period, cumulative 12-month costs, and incremental costs per quality-adjusted life year (QALY) were assessed from the societal perspective. RESULTS: In the endovascular revascularization group, 73% (55 patients) had iliac disease vs 27% (20 patients) femoral disease. Stents were used in 46/71 iliac lesions (34 patients) and in 20/40 femoral lesions (16 patients). In the supervised hospital-based exercise group, 68% (51 patients) had iliac disease vs 32% (24 patients) with femoral disease. There was a non-significant difference in the adjusted 6- and 12-month EuroQol, rating scale, and SF36-physical functioning values between the treatment groups. The gain in total mean QALYs accumulated during 12 months, adjusted for baseline values, was not statistically different between the groups (mean difference revascularization versus exercise 0.01; 99% CI -0.05, 0.07; P = .73). The total mean cumulative costs per patient was significantly higher in the revascularization group (mean difference euro2318; 99% CI 2130 euros, 2506 euros; P < .001) and the incremental cost per QALY was 231 800 euro/QALY adjusted for the baseline variables. One-way sensitivity analysis demonstrated improved effectiveness after revascularization (mean difference 0.03; CI 0.02, 0.05; P < .001), making the incremental costs 75 208 euro/QALY. CONCLUSION: In conclusion, there was no significant difference in effectiveness between endovascular revascularization compared to supervised hospital-based exercise during 12-months follow-up, any gains with endovascular revascularization found were non-significant, and endovascular revascularization costs more than the generally accepted threshold willingness-to-pay value, which favors exercise.