Would treatment decisions about secondary prevention of CVD based on estimated lifetime benefit rather than 10-year risk reduction be cost-effective?

OBJECTIVE: To test the hypothesis that treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years. METHODS: A microsimulation model was constructed for 10,000 patients with stable cardiovascular disease (CVD). Costs and quality-adjusted life years (QALYs) due to recurrent cardiovascular events and (non)vascular death were estimated for lifetime benefit-based compared to 10-year risk-based treatment, with PCSK9 inhibition as an illustration example. Lifetime benefit in months gained and 10-year absolute risk reduction were estimated using the SMART-REACH model, including an individualized treatment effect of PCSK9 inhibitors based on baseline low-density lipoprotein cholesterol. For the different numbers of patients treated (i.e. the 5%, 10%, and 20% of patients with the highest estimated benefit of both strategies), cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER), indicating additional costs per QALY gain. RESULTS: Lifetime benefit-based treatment of 5%, 10%, and 20% of patients with the highest estimated benefit resulted in an ICER of €36,440/QALY, €39,650/QALY, or €41,426/QALY. Ten-year risk-based treatment decisions of 5%, 10%, and 20% of patients with the highest estimated risk reduction resulted in an ICER of €48,187/QALY, €53,368/QALY, or €52,390/QALY. CONCLUSION: Treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years.

Are there gender disparities in symptom presentation or triage of patients with chest discomfort at primary care out-of-hours services? An observational study.

OBJECTIVES: Previous hospital-based studies have suggested delayed recognition of acute coronary syndrome (ACS) in women. We wanted to assess differences in symptom presentation or triage among women and men who contacted primary care out-of-hours services (OHS) for chest discomfort. DESIGN: Retrospective observational study. SETTING: Primary care OHS. PARTICIPANTS: 276 women and 242 men with chest discomfort who contacted a primary care OHS in the Netherlands in 2013 and 2014. MAIN OUTCOME MEASURES: Differences between women and men regarding symptom presentation and urgency allocation. RESULTS: 8.4% women and 14.0% men had ACS. Differences in symptoms between patients with and without ACS were in general small, for both women and men. In women with ACS compared with women without ACS, mean duration of telephone calls was discriminative; 5.22 (SD 2.53) vs 7.26 (SD 3.11) min, p value=0.003. In men, radiation of pain (89.3% vs 54.9%, p value=0.011) was discriminative for ACS, and stabbing chest pain (3.7% vs 24.0%, p value=0.014) for absence of ACS . Women and men with chest discomfort received similar high urgency allocation (crude and adjusted OR after correction for ACS and age; 1.03 (95% CI 0.72 to 1.48) and 1.04 (95% CI 0.72 to 1.52), respectively). Women with ACS received a high urgency allocation in 22/23 (95.7%) and men with ACS in 30/34 (88.2%), p value=0.331. CONCLUSIONS: Discriminating ACS in patients with chest discomfort who contacted primary care OHS is difficult in both women and men. Women and men with chest discomfort received similar high urgency allocation.

Cost-effectiveness of PCSK9 inhibition in addition to standard lipid-lowering therapy in patients at high risk for vascular disease.

BACKGROUND: As proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibodies are entering the market, we assessed the cost-effectiveness of PCSK9 inhibition added to standard lipid-lowering therapy in patient groups at high risk for major adverse cardiovascular events (MACE). METHODS: A lifetime Markov Model was designed to estimate healthcare costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for PCSK9 inhibition added to standard therapy in patients with Familial Hypercholesterolemia (FH), patients with vascular disease at high MACE recurrence risk, and patients with vascular disease with diabetes mellitus. The balance between costs and health outcomes was established for a broad range of potential relative risk reductions and drug costs. RESULTS: The expected QALY gain per patient and ICER in the main scenario were 1.4 QALYs for €78,485/QALY gained in patients with FH, 0.22 QALYs for €176,735/QALY gained in those with vascular disease and a predicted risk of MACE ≥30% in 10years, and 0.22 QALYs for €295,543/QALY gained in those with vascular disease and diabetes. Results were sensitive to assumptions on PCSK9 inhibitor treatment efficacy, and vascular event risks. CONCLUSION: The costs and effects of PCSK9 inhibition added to standard lipid-lowering treatment in patient groups at high risk for MACE can be estimated and adapted to a specific clinical setting. PCSK9 inhibition could be cost-effective in patients with FH. In patients with vascular disease PCSK9 inhibition is less cost-effective, however, a price development may change clinical practice. This model may aid treatment and reimbursement decisions regarding PCSK9 inhibitors.

Cost-Effectiveness of Intensifying Lipid-Lowering Therapy With Statins Based on Individual Absolute Benefit in Coronary Artery Disease Patients.

BACKGROUND: A validated prediction model estimates the absolute benefit of intensive versus standard lipid-lowering therapy (LLT) with statins on next major cardiovascular events for individual patients with coronary artery disease. We aimed to assess whether targeting intensive LLT therapy to coronary artery disease patients with the highest predicted absolute benefit is cost-effective compared to treating all with standard or all with intensive LLT. METHODS AND RESULTS: A lifetime Markov model was constructed for coronary artery disease patients (n=10 000) with mean age 61 years. Number of major cardiovascular events, (non) vascular death, costs, and quality-adjusted life years (QALYs) were estimated for the following strategies: (1) standard LLT for all (reference strategy); (2) intensive LLT for those with 5-year absolute major cardiovascular events risk reduction (ARR) ≥3%, ≥2.3%, or ≥1.5% (corresponding to ≥20%, ≥15%, or ≥10% 5-year major cardiovascular events risk); and (3) intensive LLT for all. With intensive LLT for those with ≥3% 5-year ARR (13% of patients), 380 QALYs were gained for €2423/QALY. Using a threshold of ≥2.3% ARR (26% of patients), 630 QALYs were gained for €5653/QALY. Using a threshold of ≥1.5% ARR (56% of patients), 1020 QALYs were gained for €10 960/QALY. By treating all intensively, 1410 QALYs were gained (0.14 QALY per patient) for €17 223/QALY. With benefit-based treatment, 0.16 to 0.17 QALY was gained per treated patient. CONCLUSIONS: Intensive LLT with statins for all coronary artery disease patients results in the highest overall QALY gain against acceptable costs. However, the number of QALYs gained with intensive LLT by statins in individual patients can be increased with selective benefit-based treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00327691 and NCT00159835.

Gender difference in long-term prognosis among patients with cardiovascular disease.

BACKGROUND: Differences in prognosis between women and men with atherosclerosis are currently under attention. Previous studies describe contradictory results and are restricted to one cardiovascular bed, while atherosclerosis is a systemic disease. We therefore studied the prognosis of women versus men in the SMART study, a large cohort of patients with clinically manifest atherosclerosis with extensive baseline and follow-up information. METHODS: 5349 patients (1347 women, 4002 men) with at least one type of atherosclerotic vascular disease (coronary artery disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm) were included in the SMART study, an ongoing long-term follow-up study. They all received a standardized cardiovascular work-up with a personalized therapy advice. All future cardiovascular events were collected prospectively. All-cause mortality, cardiovascular mortality and cardiovascular outcome (composite of myocardial infarction, stroke and cardiovascular death) were evaluated using Cox regression and expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). Men served as the reference category. Different models were used to adjust for differences in baseline characteristics. RESULTS: Women and men had a mean age of 60 years and their median follow-up (range) was five years (13.5). The hazard ratios of all-cause mortality, cardiovascular death and cardiovascular outcome were 0.62 (95%CI: 0.51-0.75), 0.59 (95%CI: 0.46-0.75) and 0.73 (95%CI: 0.60-0.87). Neither differences in risk-factor profile nor the different vascular beds involved could explain this advantage. CONCLUSION: Women with cardiovascular disease who received a similar standardized cardiovascular work-up and personalized therapy advice as men had a favourable long-term outcome.

Reliability of visual assessment of non-contrast CT, CT angiography source images and CT perfusion in patients with suspected ischemic stroke.

BACKGROUND AND PURPOSE: Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke. METHODS: We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement. RESULTS: Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps. CONCLUSION: Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.

Intra and interobserver reliability and agreement of semiquantitative vertebral fracture assessment on chest computed tomography.

OBJECTIVES: To evaluate the reliability of semiquantitative Vertebral Fracture Assessment (VFA) on chest Computed Tomography (CT). METHODS: Four observers performed VFA twice upon sagittal reconstructions of 50 routine clinical chest CTs. Intra- and interobserver agreement (absolute agreement or 95% Limits of Agreement) and reliability (Cohen's kappa or intraclass correlation coefficient(ICC)) were calculated for the visual VFA measures (fracture present, worst fracture grade, cumulative fracture grade on patient level) and for percentage height loss of each fractured vertebra compared to the adjacent vertebrae. RESULTS: Observers classified 24-38% patients as having at least one vertebral fracture, giving rise to kappa's of 0.73-0.84 (intraobserver) and 0.56-0.81 (interobserver). For worst fracture grade we found good intraobserver (76-88%) and interobserver (74-88%) agreement, and excellent reliability with square-weighted kappa's of 0.84-0.90 (intraobserver) and 0.84-0.94 (interobserver). For cumulative fracture grade the 95% Limits of Agreement were maximally ±1,99 (intraobserver) and ±2,69 (interobserver) and the reliability (ICC) varied from 0.84-0.94 (intraobserver) and 0.74-0.94 (interobserver). For percentage height-loss on a vertebral level the 95% Limits of Agreement were maximally ±11,75% (intraobserver) and ±12,53% (interobserver). The ICC was 0.59-0.90 (intraobserver) and 0.53-0-82 (interobserver). Further investigation is needed to evaluate the prognostic value of this approach. CONCLUSION: In conclusion, these results demonstrate acceptable reproducibility of VFA on CT.

Data Resource Profile: adult cardiac surgery database of the Netherlands Association for Cardio-Thoracic Surgery.

In 2007 The Netherlands Association for Cardio-Thoracic Surgery (Nederlandse Vereniging voor Thoraxchirurgie, NVT) instituted the Adult Cardiac Surgery Database. The dataset comprises demographic factors, type of intervention, in-hospital mortality and 18 risk factors for mortality after cardiac surgery, according to the European System for Cardiac Operative Risk Evaluation definitions. Currently, this procedural database contains over 60 000 interventions. Completeness of data is excellent and national coverage of all 16 Dutch cardio-thoracic surgery centres has been achieved since the start. The primary goal of the database is to control and maintain the quality of care by evaluation of outcomes. This is accomplished by regular feedback and comparison of outcomes. For a subset of the database (procedures from 10 out of 16 centres) longer-term follow-up has been established by means of data linkage to two national registries. This provides information on survival status, causes of death and readmissions. The database has recently been used for research, resulting in methodological papers aimed at optimizing comparison of outcomes. In future, clinical issues will also be addressed, for example survival after coronary artery bypass grafting and valve surgery.

The daily 10 kcal expenditure deficit: a before-and-after study on low-cost interventions in the work environment.

OBJECTIVES: To evaluate whether four types of low-cost interventions in the working environment can promote the small everyday lifestyle adaptations that can halt the epidemics of obesity and hypertension when maintained long term. DESIGN: A single-blind uninterrupted time-series intervention study consisting of four study periods: run-in (2 weeks), baseline (2 weeks), intervention (2 weeks), and after intervention 2 weeks). SETTING: University Medical Centre with over 11 000 employees, over 1000 hospital beds and over 2000 customers visiting the hospital restaurant each day. PARTICIPANTS: Hospital staff and visitors. INTERVENTIONS: (1) Point-of-decision prompts on hospital elevator doors promoting stair use. (2) Point-of-purchase prompts in the hospital restaurant promoting reduced-salt soup. (3) Point-of-purchase prompts in the hospital restaurant promoting lean croissants. (4) Reversal of the accessibility and availability of diet margarine and butter in the hospital restaurant. MAIN OUTCOME MEASURES: (1) Number of passages through 15 different parts of the hospital staircases. (2) Number and ratio of normal-salt and reduced-salt soup purchased. (3) Number and ratio of butter croissants and lean croissants purchased. (4) Number and ratio of diet margarine and butter purchased. RESULTS: Elevator signs increased the mean 24-h number of stair passages per measurement site (baseline: 992 ± 479 on week days and 208 ± 116 on weekend days) by 11.2% (95% CI 8.7% to 13.7%). This effect was maintained at least 2 weeks after the point-of-decision prompts were removed. Point-of-purchase prompts promoting low-salt soup and lean croissants did not result in altered purchase behaviour. The ratio between the purchase of margarine and butter was changed sevenfold (p<0.01) by reversing the positions of these products in the hospital restaurant. CONCLUSIONS: Healthy lifestyle adaptations in the working environment can be effectively promoted by making healthy choices easier than unhealthy ones. Educational prompts at points-of-decision moderately increase stair climbing, but do not affect healthy food choices. PROTOCOL REGISTRATION: Clinicaltrials.gov identifier number: NCT01574040.

Clinical outcome of implant removal after fracture healing. Design of a prospective multicentre clinical cohort study.

BACKGROUND: The clinical results of removal of metal implants after fracture healing are unknown and the question whether to remove or to leave them in is part of discussion worldwide. We present the design of a prospective clinical multicentre cohort study to determine the main indications for and expectations of implant removal, the influence on complaints, the incidence of surgery related complications and the socio-economic consequences of implant removal. METHODS/DESIGN: In a prospective multicentre clinical cohort study at least 200 patients with a healed fracture after osteosynthesis with a metal implant are included for analyzing the outcome after removal. Six hospitals in the Netherlands are participating. Special questionnaires are designed. The follow up after surgery will be at least six months. The primary endpoint is the incidence of surgery related complications. Secondary endpoints are the influence of removal on preoperative symptoms and complaints and the socio-economic consequences. DISCUSSION: By performing this study we hope to find profound arguments to remove or not to remove metal implants after fracture healing that can help to develop clear guidelines for daily practice. TRIAL REGISTRATION: NTR1297, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1297.

Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial.

BACKGROUND: Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. METHODS: Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. FINDINGS: Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. INTERPRETATION: In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. FUNDING: ZonMw; COOK Medical.

Cost-effectiveness of magnetic resonance angiography versus intra-arterial digital subtraction angiography to follow-up patients with coiled intracranial aneurysms.

BACKGROUND AND PURPOSE: To follow up patients with coiled intracranial aneurysms, magnetic resonance angiography (MRA) is a promising noninvasive alternative to current standard intra-arterial digital subtraction angiography (IA-DSA). MRA test results do not always concord with those of IA-DSA, and the impact of discrepancies on health benefits and costs is unknown. We evaluated the cost-effectiveness of follow-up with MRA vs IA-DSA to assess whether in this setting MRA may replace IA-DSA. METHODS: We studied aneurysm occlusion on MRA in addition to follow-up IA-DSA in 310 patients with 341 coiled intracranial aneurysms. The observed sensitivity (82%) and specificity (89%) of MRA for detection of reopening with IA-DSA as a reference were used as input for a Markov decision-analytic model. Other determinants were derived from the literature. We compared life expectancy, quality-adjusted life-years (QALY), costs, and expected number of events for the two strategies. RESULTS: Follow-up with MRA yielded similar life expectancy (MRA, 26.66 years; IA-DSA, 26.63 years; difference, 0.03 years; 95% CI, -0.17-0.23) and QALY (MRA, 10.96; IA-DSA, 10.95; difference, 0.01 QALY; 95% CI, -0.05-0.08) at lower costs (MRA, $7003; IA-DSA, $8241 per patient; difference, -$1238; 95% CI, -2617--36). The expected number of events was comparable except for complications from IA-DSA. CONCLUSIONS: MRA provided equivalent health benefits as IA-DSA and was cost-saving. MRA dominates and should replace routine IA-DSA to follow-up patients with coiled aneurysms.

Quality of life in patients with no-option critical limb ischemia underlines the need for new effective treatment.

OBJECTIVE: To provide a solid baseline reference for quality of life (QoL) in patients with no-option critical limb ischemia (CLI). CLI is associated with surgery, endovascular interventions, hospitalization, and a poor prognosis. An increasing number of clinical trials are, therefore, investigating new treatment strategies (eg, therapeutic neovascularization) in patients with CLI. QoL serves as an important secondary endpoint in many of these trials, but solid reference QoL data for patients with no-option CLI are lacking. METHODS: The Medical Outcomes Study Short Form 36 (SF-36) and the EuroQol-5D (EQ-5D) questionnaires were used to obtain baseline QoL scores from 47 patients with no-option CLI participating in a therapeutic neovascularization trial. To allow for easy comparability, a norm-based scoring (NBS) method was used to report the results of the SF-36. Scores of patients with CLI were furthermore compared with scores of patients with milder forms of peripheral arterial disease (PAD) and with patients with cardiovascular risk factors only. Determinants of QoL in patients with PAD were identified using multiple linear regression methods. RESULTS: Patients with no-option CLI reported QoL scores below the general population mean on every health dimension of the SF-36. Physical functioning, role physical functioning, and bodily pain were affected most intensively. These poor physical QoL scores were further underlined when compared with other patients with milder forms of PAD or patients with cardiovascular risk factors only. Patients with CLI scored poorly on the pain/discomfort and the usual activities domain of the EQ-5D. Diabetes, female gender, body mass index, and the ankle-brachial index at rest were significant determinants of the QoL in PAD on multivariate analysis. CONCLUSION: The QoL data of patients with no-option CLI using NBS methods for the SF-36 provide a baseline reference for ongoing clinical trials on new treatment strategies. Our data stress the need for new revascularization therapies in patients with no-option CLI.

Towards a more efficient diabetes control in primary care: six-monthly monitoring compared with three-monthly monitoring in type 2 diabetes - The EFFIMODI trial. Design of a randomised controlled patient-preference equivalence trial in primary care.

BACKGROUND: Scientific evidence for the frequency of monitoring of type 2 diabetes patients is lacking. If three-monthly control in general practice could be reduced to six-monthly control in some patients, this would on the one hand reduce the use of medical services including involvement of practice nurses, and thus reduce costs, and on the other hand alleviate the burden of people with type 2 diabetes. The goal of this study is to make primary diabetes care as efficient as possible for patients and health care providers. Therefore, we want to determine whether six-monthly monitoring of well-controlled type 2 diabetes patients in primary care leads to equivalent cardiometabolic control compared to the generally recommended three-monthly monitoring. METHODS AND DESIGN: The study is a randomised controlled patient-preference equivalence trial. Participants are asked if they prefer three-monthly (usual care) or six-monthly diabetes monitoring. If they do not have a preference, they are randomised to a three-monthly or six-monthly monitoring group. Patients are eligible for the study if they are between 40 and 80 years old, diagnosed with type 2 diabetes more than one year ago, treated by a general practitioner, not on insulin treatment, and with HbA1c < or = 7.5%, systolic blood pressure < or = 145 mmHg and total cholesterol < or = 5.2 mmol/l. The intervention group (six-monthly monitoring) will receive the same treatment with the same treatment targets as the control group (three-monthly monitoring). The intervention period will last one and a half year. After the intervention, the three-monthly and six-monthly monitoring groups are compared on equivalence of cardiometabolic control. Secondary outcome measures are HbA1c, blood pressure, cholesterol level, Body Mass Index, smoking behaviour, physical activity, loss of work due to illness, health status, diabetes-specific distress, satisfaction with treatment and adherence to medications. We will use intention-to-treat analysis with repeated measures. For outcomes that have only baseline and final measurements, we will use ANCOVA. Depending on the results, a cost-minimisation analysis or an incremental cost-effectiveness analysis will be done. DISCUSSION: This study will provide valuable information on the most efficient control frequency of well-controlled type 2 diabetes patients in primary care.

Semiquantitative assessment of cardiovascular disease markers in multislice computed tomography of the chest: interobserver and intraobserver agreements.

OBJECTIVE: To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings. METHODS: Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast-enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients. RESULTS: Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement. CONCLUSIONS: Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT.

Prediction rule for cardiovascular events and mortality in peripheral arterial disease patients: data from the prospective Second Manifestations of ARTerial disease (SMART) cohort study.

BACKGROUND: Patients with peripheral arterial disease (PAD) are at high risk of secondary cardiovascular death and events such as myocardial infarction or stroke. To minimize this elevated risk, cardiovascular risk factors should be treated in all PAD patients. Secondary risk management may benefit from a prediction tool to identify PAD patients at the highest risk who could be referred for an additional extensive workup. Stratifying PAD patients according to their risk of secondary events could aid in achieving optimal therapy compliance. To this end we developed a prediction model for secondary cardiovascular events in PAD patients. METHODS: The model was developed using data from 800 PAD patients who participated in the Second Manifestations of ARTerial disease (SMART) cohort study. From the baseline characteristics, 13 candidate predictors were selected for the model development. Missing values were imputed by means of single regression imputation. Continuous predictors were truncated and transformed where necessary, followed by model reduction by means of backward stepwise selection. To correct for over-fitting, a bootstrapping technique was applied. Finally, a score chart was created that divides patients in four risk categories that have been linked to the risk of a cardiovascular event during 1- and 5-year follow-up. RESULTS: During a mean follow-up of 4.7 years, 120 events occurred (27% nonfatal myocardial infarction, 21% nonfatal stroke, and 52% mortality from vascular causes), corresponding to a 1- and 5-year cumulative incidence of 3.1% and 13.2%, respectively. Important predictors for the secondary risk of a cardiovascular event are age, history of symptomatic cardiovascular disease, systolic blood pressure, high-density lipoprotein cholesterol, smoking behavior, ankle-brachial pressure index, and creatinine level. The risk of a cardiovascular event in a patient as predicted by the model was 0% to 10% and 1% to 28% for the four risk categories at 1- and 5-year follow-up, respectively. The discriminating capacity of the prediction model, indicated by the c statistic, was 0.76 (95% confidence interval, 0.71-0.80). CONCLUSION: A prediction model can be used to predict secondary cardiovascular risk in PAD patients. We propose such a prediction model to allow for the identification of PAD patients at the highest risk of a cardiovascular event or cardiovascular death, which may be a viable tool in vascular secondary health care practice.

Protocol for Physiotherapy Or TVT Randomised Efficacy Trial (PORTRET): a multicentre randomised controlled trial to assess the cost-effectiveness of the tension free vaginal tape versus pelvic floor muscle training in women with symptomatic moderate to severe stress urinary incontinence.

BACKGROUND: Stress urinary incontinence is a common condition affecting approximately 20% of adult women causing substantial individual (quality of life) and economic (119 million Euro/year spent on incontinence pads in the Netherlands) burden. Pelvic floor muscle training (PFMT) is regarded as first line treatment, but only 15-25% of women will be completely cured. Approximately 65% will report that their condition improved, but long term adherence to treatment is problematic. In addition, at longer term (2-15 years) follow-up 30-50% of patients will end up having surgery. From 1996 a minimal invasive surgical procedure, the Tension-free Vaginal Tape (TVT) has rapidly become the gold standard in surgical treatment of stress urinary incontinence. With TVT 65-95% of women are cured. However, approximately 3-6% of women will develop symptoms of an overactive bladder, resulting in reduced quality of life. Because of its efficacy the TVT appears to be preferable over PFMT but both treatments and their costs have not been compared head-to-head in a randomised clinical trial. METHODS/DESIGN: A multi-centre randomised controlled trial will be performed for women between 35-80 years old with moderate to severe, predominantly stress, urinary incontinence, who have not received specialised PFMT or previous anti-incontinence surgery. Women will be assigned to either PFMT by a specialised physiotherapist for a standard of 9-18 session in a period of 6 months, or TVT(O) surgery. The main endpoint of the study is the subjective improvement of urinary incontinence. As secondary outcome the objective cure will be assessed from history and clinical parameters. Subjective improvement in quality of life will be measured by generic (EQ-5D) and disease-specific (Urinary Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments. The economical endpoint is short term (1 year) incremental cost-effectiveness in terms of costs per additional year free of urinary incontinence and costs per Quality Adjusted Life Years (QALY) gained. Finally, treatment strategy and patient characteristics will be combined in a prediction model, to allow for individual treatment decisions in future patients. Four hundred female patients will be recruited from over 30 hospitals in the Netherlands. TRIAL REGISTRATION: Nederlands trial register: NTR 1248.

Decision analysis to complete diagnostic research by closing the gap between test characteristics and cost-effectiveness.

OBJECTIVE: The lack of a standard methodology in diagnostic research impedes adequate evaluation before implementation of constantly developing diagnostic techniques. We discuss the methodology of diagnostic research and underscore the relevance of decision analysis in the process of evaluation of diagnostic tests. STUDY DESIGN AND SETTING: Overview and conceptual discussion. RESULTS: Diagnostic research requires a stepwise approach comprising assessment of test characteristics followed by evaluation of added value, clinical outcome, and cost-effectiveness. These multiple goals are generally incompatible with a randomized design. Decision-analytic models provide an important alternative through integration of the best available evidence. Thus, critical assessment of clinical value and efficient use of resources can be achieved. CONCLUSION: Decision-analytic models should be considered part of the standard methodology in diagnostic research. They can serve as a valid alternative to diagnostic randomized clinical trials (RCTs).

Is centralization of ovarian cancer care warranted? A cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of tertiary referral care for ovarian cancer patients in the Netherlands. METHODS: We collected clinical and registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996-2003 in a random sample of Dutch hospitals. Decision modelling was used to compare the cost-effectiveness of treatment in general hospitals, semi-specialized hospitals, and tertiary care centers. The actual direct medical costs of ovarian cancer treatment were evaluated. Long-term outcomes in terms of costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained were estimated. To assess uncertainty, multivariable sensitivity analyses and scenario analyses were performed. RESULTS: Treatment of ovarian cancer patients in semi-specialized hospitals costs on average euro882 more than in general hospitals (95% confidence interval -720 to 2462) and yields 0.12 additional QALYs (95% CI 0.02 to 0.22), resulting in an incremental cost-effectiveness ratio (ICER) of euro7135. Patients treated in tertiary care centers incurred again higher costs (euro10,591, 95% CI 8757 to 12,480) and also higher QALYs (0.10, 95% CI 0 to 0.21), resulting in an ICER of euro102,642 compared to semi-specialized hospitals. If the optimal debulking rate in tertiary care centers would increase to 70%, costs could drop below euro30,000 per QALY. CONCLUSION: Current treatment of ovarian cancer patients in semi-specialized hospital settings is a cost-effective strategy, while treatment in tertiary care centers becomes only cost-effective when better surgical results would be achieved.

Chest radiography in general practice: indications, diagnostic yield and consequences for patient management.

BACKGROUND: Chest radiography (CXR) is frequently performed in Western societies. There is insufficient knowledge of its diagnostic value in terms of changes in patient management decisions in primary care. AIM: To assess the influence of CXR on patient management in general practice. DESIGN OF STUDY: Prospective cohort study. SETTING: Seventy-eight GPs and three general hospitals in the Netherlands. METHOD: Patients (n = 792) aged > or =18 years referred by their GPs for CXR were included. The main outcome was change in patient management assessed by means of questionnaires filled in by GPs before and after CXR. RESULTS: Mean age of the patients was 57.3+/-16.2 years and 53% were male. Clinically relevant abnormalities were found in 24% of the CXRs. Patient management changed in 60% of the patients following CXR. Main changes included: fewer referrals to a medical specialist (from 26 to 12%); reduction in initiation or change in therapy (from 24 to 15%); and more frequent reassurance (from 25 to 46%). However, this reassurance was not perceived as such in a quarter of these patients. A change in patient management occurred significantly more frequently in patients with complaints of cough (67%), those who exhibited abnormalities during physical examination (69%), or those with a suspected diagnosis of pneumonia (68%). CONCLUSION: Patient management by the GP changed in 60% of patients following CXR. CXR substantially reduced the number of referrals and initiation or change in therapy, and more patients were reassured by their GP. Thus, CXR is an important diagnostic tool for GPs and seems a cost-effective diagnostic test.