Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Construct validity of the PROMIS PF-10 in patients with inflammatory rheumatic diseases and severe limitations in physical functioning.

OBJECTIVE: Assessing the construct validity of the Patient-Reported Outcomes Measurement Information System Physical Function 10-Item Short Form (PROMIS PF-10) in a subpopulation of rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) patients with severe limitations in physical functioning (PF). METHOD: RA/axSpA patients with severe functional limitations completed the PROMIS PF-10, Health Assessment Questionnaire - Disability Index (HAQ-DI for RA) or Bath Ankylosing Spondylitis Functional Index (BASFI for axSpA), 36-item Short Form Health Survey (SF-36), EuroQol 5-dimensions 5-level (index score, EQ-VAS), and performed the Six-Minute Walk Test (6MWT). Construct validity was assessed by computing Spearman rank or Pearson correlation coefficients and testing hypotheses about correlations between the PROMIS PF-10 and measures of PF and quality of life. RESULTS: Data from 316 patients (180 RA/136 axSpA, 91.7%/47.8% female, mean ± sd age 58.6 ± 13.2/54.0 ± 11.3 years) were analysed. The median (IQR) PROMIS PF-10 score was 34.5 (31.4-37.6) in RA and 36.0 (32.8-38.3) in axSpA patients. The PROMIS PF-10 correlated strongly with the HAQ-DI, BASFI, and EQ-5D-5L index score (r > 0.6), moderately with the SF-36 Physical Component Summary score, EQ-VAS, and 6MWT (0.30 ≤ r ≤ 0.60), and weakly with the SF-36 Mental Component Summary score (r < 0.30). Five of six hypotheses (83%) were confirmed in both groups. CONCLUSION: The overall strong correlation of the PROMIS PF-10 with measures of PF and moderate to weak correlations with outcomes measuring different constructs were confirmed in subpopulations of RA and axSpA patients with severe functional limitations, supporting its construct validity.

Multicentre randomized clinical trial to investigate the cost-effectiveness of an allogeneic single-donor fibrin sealant after coronary artery bypass grafting (FIBER Study).

BACKGROUND: Reduction of blood transfusion in cardiac surgery is an important target. The aim of this study was to investigate the cost-effectiveness of the use of CryoSeal®, an allogeneic single-donor fibrin sealant, in patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized clinical study involved seven cardiac surgery centres in the Netherlands. Patients undergoing elective isolated CABG with the use of at least one internal thoracic artery (ITA) graft were assigned randomly to receive either CryoSeal® (5 ml per ITA bed) or no CryoSeal®. Primary efficacy endpoints were units of transfused red blood cells, fresh frozen plasma and platelet concentrates, and duration of intensive care unit stay. Secondary efficacy endpoints were 48-h blood loss, reoperation for bleeding, mediastinitis, 30-day mortality and duration of hospital stay. RESULTS: Between March 2009 and January 2012, 1445 patients were randomized. The intention-to-treat (ITT) population comprised 1436 patients; the per-protocol (PP) population 1292. In both the ITT and the PP analysis, no significant difference between the treatment groups was observed for any of the primary and secondary efficacy endpoints. In addition, no significant difference between the groups was seen in the proportion of transfused patients. Estimated CryoSeal® costs were €822 (95 per cent c.i. €808 to €836) per patient, which translated to €72,000 per avoided transfusion (unbounded 95 per cent c.i.). CONCLUSION: The use of the fibrin sealant CryoSeal® did not result in health benefits. Combined with the high cost per avoided transfusion, this study does not support the implementation of routine CryoSeal® use in elective isolated CABG. REGISTRATION NUMBER: NTR1386 ( http://www.trialregister.nl).

Effectiveness and cost-effectiveness of a multimodal, physiotherapist-led, vocational intervention in people with inflammatory arthritis: study protocol of the Physiotherapy WORKs trial.

BACKGROUND: Although reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care. METHODS: This randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index - Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group. DISCUSSION: The results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability. TRIAL REGISTRATION: This study is registered in the International Clinical Trial Registry Platform (ICTRP) under number NL9343.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

The value of productivity: human-capital versus friction-cost method.

Many cost-of-illness studies have investigated the impact of rheumatoid arthritis on productivity, invariably concluding that productivity costs are high. Different methods exist to value productivity. The human-capital method takes the patient's perspective and counts any hour not worked as an hour lost. By contrast, the friction-cost method takes the employer's perspective, and only counts as lost those hours not worked until another employee takes over the patient's work. Both methods can produce widely different results. Productivity costs have the potential to compensate for the costs of expensive biological agents, but only in early-onset disease when patients still have jobs and if productivity is given full weight by using the human-capital method. If productivity is given less weight by excluding productivity costs or by using the friction-cost method, then currently, biological agents are probably too expensive.

The impact of new evidence on regional variation in paediatric tonsillectomy and adenoidectomy: a historical review.

BACKGROUND: Tonsillectomy and adenoidectomy have been among the most commonly performed procedures in children for approximately 100 years. These procedures were the first for which unwarranted regional variation was discovered, in 1938. Indications for these procedures have become stricter over time, which might have reduced regional practice variation. METHODS: This paper presents a historical review on practice variation in paediatric tonsillectomy and adenoidectomy rates. Data on publication year, region, level of variation, methodology and outcomes were collected. RESULTS: Twenty-one articles on practice variation in paediatric tonsil surgery were included, with data from 12 different countries. Significant variation was found throughout the years, although a greater than 10-fold variation was observed only in the earliest publications. CONCLUSION: No evidence has yet been found that better indications for tonsillectomy and adenoidectomy have reduced practice variation. International efforts are needed to reconsider why we are still unable to tackle this variation.

[The effect of the risk of a complaint on treatment decision making. An explorative investigation in fourth-year dental students]. / Het effect van de klachtkans op een behandelbeslissing. Een exploratief onderzoek onder vierdejaarsstudenten tandheelkunde.

The perception of the seriousness of a false-negative or false-positive diagnosis could influence treatment decision making for carious lesions. In order to investigate this hypothesis, the perceived risk of a complaint at a disciplinary tribunal was used as an indicator of the seriousness of the consequences of treatment decision errors. Using a computer programme for caries diagnosis on radiographs and by means of a questionnaire, was investigated in a group of fourth-year dental students whether their accuracy of treatment decision making for carious lesions was dependent on the perception of the risk of a complaint at a disciplinary tribunal. The perception of the likelihood of complaints does not seem to play a significant role in the accuracy of decision making. However, the students demonstrated unrealistical high risk perceptions of a complaint at a disciplinary tribunal following a treatment decision making error by a false diagnosis of a carious lesion on a bitewing radiograph.

Healthcare utilization in chronic thromboembolic pulmonary hypertension after acute pulmonary embolism.

Essentials Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) is long. We explored healthcare utilisation of patients diagnosed with CTEPH after pulmonary embolism. A large number of physicians were consulted and test results were not always interpreted correctly. Better education and higher awareness of CTEPH may lead to faster diagnosis. SUMMARY: Background The median diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) is 14 months, which may affect prognosis. We aimed to explore the healthcare utilization of patients diagnosed with CTEPH after acute pulmonary embolism (PE), and to identify the causes of diagnostic delay. Methods We collected all data on patient symptoms, medical specialist referrals and ordered diagnostic tests to reconstruct the clinical pathways of 40 patients referred to the VU University Medical Center Amsterdam (VUMC, the Netherlands) for CTEPH treatment. Diagnostic delay was defined as the time between first symptom onset and referral to the VUMC. Correlations of patient-specific characteristics and diagnostic delay were evaluated. Results Patients consulted four (median) different physicians for a median of 13 (interquartile range [IQR] 10-18) consultations before the correct diagnosis was made. The median diagnostic delay was 21 months (IQR 12-49 months). Echocardiographic results suggestive of CTEPH were not always followed by an adequate work-up; most patients were not subjected to ventilation/perfusion scanning. Prior cardiopulmonary comorbidity and recurrent venous thromboembolism were predictors of a longer delay. Conclusion Healthcare utilization in patients before their final CTEPH diagnosis was far from optimal, contributing to a considerable diagnostic delay. Better education and higher awareness of CTEPH among PE caretakers may lead to faster diagnosis.

Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe.

Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value. We performed a literature search covering PubMed, Embase, Web of Science and Cochrane, for studies related to one or more of the four selected assays. We identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX both have evidence available, including level IA clinical trial results for both assays. Both assays provide prognostic information. Predictive value has only been shown for OncotypeDX. In the clinical utility studies, a higher reduction in chemotherapy was achieved by OncotypeDX, although the number of available studies differ considerably between tests. On average, economic evaluations estimate that genomic testing results in a moderate increase in total costs, but that these costs are acceptable in relation to the expected improved patient outcome. PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with less economical and clinical utility studies. Furthermore, for these assays no level IA trial data are available yet. In summary, all assays have shown excellent prognostic capacities. The differences in the quantity and quality of evidence are discussed. Future studies shall focus on the selection of appropriate subgroups for testing and long-term outcome of validation trials, in order to determine the place of these assays in daily clinical practice.

The YEARS algorithm for suspected pulmonary embolism: shorter visit time and reduced costs at the emergency department.

Essentials The YEARS algorithm was designed to simplify the diagnostic workup of suspected pulmonary embolism. We compared emergency ward turnaround time of YEARS and the conventional algorithm. YEARS was associated with a significantly shorter emergency department visit time of ˜60 minutes. Treatment of pulmonary embolism was initiated 53 minutes earlier with the YEARS algorithm SUMMARY: Background Recently, the safety of the YEARS algorithm, designed to simplify the diagnostic work-up of pulmonary embolism (PE), was demonstrated. We hypothesize that by design, YEARS would be associated with a shorter diagnostic emergency department (ED) visit time due to simultaneous assessment of pre-test probability and D-dimer level and reduction in number of CT scans. Aim To investigate whether implementation of the YEARS diagnostic algorithm is associated with a shorter ED visit time compared with the conventional algorithm and to evaluate the associated cost savings. Methods We selected consecutive outpatients with suspected PE from our hospital included in the YEARS study and ADJUST-PE study. Different time-points of the diagnostic process were extracted from the to-the-minute accurate electronic patients' chart system of the ED. Further, the costs of the ED visits were estimated for both algorithms. Results All predefined diagnostic turnaround times were significantly shorter after implementation of YEARS: patients were discharged earlier from the ED; 54 min (95% CI, 37-70) for patients managed without computed tomography pulmonary angiography (CTPA) and 60 min (95% CI, 44-76) for the complete study population. Importantly, patients diagnosed with PE by CTPA received the first dose of anticoagulants 53 min (95% CI, 22-82) faster than those managed according to the conventional algorithm. Total costs were reduced by on average €123 per visit. Conclusion YEARS was shown to be associated with a shorter ED visit time compared with the conventional diagnostic algorithm, leading to faster start of treatment in the case of confirmed PE and savings on ED resources.

Implementation of the laparoscopic simulator in a gynecological residency curriculum.

BACKGROUND: In view of the current emphasis on increasing patient safety and quality control in laparoscopic surgery, there is a growing need to improve laparoscopic training. This study was conducted to investigate if and when residents reached performance standards for basic laparoscopic skills on a boxtrainer and to analyze the current state of implementation of laparoscopic simulators in a gynecological residency curriculum. METHODS: Residents across all 6 years of residency (postgraduate year [PGY] 1-6) were tested once on our boxtrainer by performing five inanimate tasks (pipe cleaner, rubber band, beads, cutting circle, intracorporeal knot tying). A sumscore for the five tasks was calculated for each participant (sum of all scores). Scores were calculated by adding completion time and penalty points, thus rewarding both speed and precision. These data were compared with scores of laparoscopic experts, which were set as performance standards. RESULTS: Of the participants, 111 were residents (7 PGY1, 27 PGY2, 29 PGY3, 28 PGY4, 14 PGY5, 6 PGY6) and 8 were experts. At the end of residency, PGY6 residents reached the performance standard for all tasks except intracorporeal knot tying. It was not until PGY5 that residents reached the performance standard for the pipe cleaner task; PGY1, for rubber band; PGY5, for beads; PGY4, for circle cutting; and PGY6, for sumscore. Throughout residency PGY6 had a mean total of only 3.6 h of simulator training experience. No correlation was found between this previous voluntary simulator training experience and performance on our boxtrainer during this study (sumscore), and between previous voluntary simulator training and total laparoscopic procedures performed. In a combined multivariate analysis, sumscore performance remained significantly associated with the number of laparoscopic procedures performed by residents when they were working as as a primary surgeon (p = 0.002), and not with the cumulative hours of simulator training during residency prior to participating in this study (p = 0.15). CONCLUSIONS: In a current Dutch gynecological residency curriculum, residents do not reach all performance standards for basic laparoscopic skills on the boxtrainer. We conclude that the voluntary simulator training program has a substantial risk to fail and that the implementation of the laparoscopic skills simulator in the current residency curriculum is in its infancy.

[Early surgery or a wait-and-see policy in lumbosacral radicular syndrome: a randomized study]. / Vroeg opereren of langer afwachten voor het lumbosacraal radiculair syndroom: een gerandomiseerd onderzoek.

OBJECTIVE: To compare early surgery with expectative policy and later surgery if necessary in patients with sciatica that did not resolve within 6 weeks. DESIGN: Randomized multicentre clinical trial (ISRCTN 26872154). METHODS: Patients who had had severe sciatica for 6 to 12 weeks were randomized to early surgery or to prolonged conservative treatment with later surgery if necessary. The primary outcomes were the Roland Disability Questionnaire score, the visual-analogue scale for leg pain score, and the patient's report of their perceived recovery over the first year after randomization. Repeated measures analysis according to the intention-to-treat principle was used to analyse the outcome curves for both groups. RESULTS: A total of 283 patients were included and randomized. Of 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy after a mean of 2.2 weeks. Of 142 patients assigned to conservative treatment, 55 (39%) still had to undergo surgical treatment after a mean of 18.7 weeks. There was no significant overall difference in disability scores during the first year (p = 0.13). Leg pain lessened more quickly in patients assigned to early surgery (p < 0.001). Patients assigned to early surgery also reported a faster rate of perceived recovery (hazard ratio (HR): 1.97; 95% CI: 1.72-2.22; p < 0.001). In both groups, however, the probability of perceived recovery after 1 year of follow-up was 95%. CONCLUSIONS: The 1-year outcomes were similar for patients assigned to early surgery and those assigned to extended conservative treatment with later surgery if necessary but the rates of reduction of leg pain and of perceived recovery were faster in those assigned to early surgery.

[Evidence-based diagnosis and clinical decision making]. / Evidence-based diagnostiek en klinische besluitvorming.

The application of evidence-based dentistry to diagnosis should result in a reduction in errors in decision making. The frequency of errors is dependent not only on the accuracy of a diagnostic test for pathology but also on the prior chance of disease being present. If this chance is low and below a certain threshold then, for example, applying a diagnostic test can result in more decision errors and therefore inappropriate treatment than omitting to use the test. In deciding on the usefulness of a diagnostic test an additional factor to take into account is the relative value of the possible health states resulting from diagnosis and subsequent therapy. These can be determined by eliciting from the patient the numerical values of the appropriate dental health conditions using a visual analogue scale technique. Although clinical decision analysis is starting to influence the development of guidelines for the diagnostic use of radiographs, its application in dentistry needs further refinement and development.

Healthcare costs and loss of productivity in patients with trapeziometacarpal osteoarthritis.

The objective of this study was to analyse healthcare and productivity costs in patients with trapeziometacarpal osteoarthritis. We included 161 patients who received surgery or steroid injection and calculated their healthcare costs in Euro (€) over 1 year. Patients filled out the Work Productivity and Activity Impairment Questionnaire to assess loss of productivity at baseline, and after 3, and 12 months. In the surgical group, loss of productivity among employed patients first increased and then decreased (50%, 64%, and 25% at 0, 3, and 12 months). Productivity was more stable over time in the injection group (52%, 38%, and 48%). In the surgical group, estimated total annual healthcare and productivity costs were €5770 and €5548, respectively. In the injection group, healthcare and productivity costs were €348 and €3503. These findings highlight the need for assessing productivity costs to get a comprehensive view of the costs associated with a treatment.Level of Evidence III.

Effect of Aerobic Exercise Training on Fatigue in Rheumatoid Arthritis: A Meta-Analysis.

OBJECTIVE: Rheumatoid arthritis (RA) fatigue is not being well-managed currently, and evidence of effective interventions is limited. Aerobic exercise may provide benefit to treat fatigue in RA. Therefore, the purpose of this meta-analysis is to analyze the effect of aerobic land-based exercise on fatigue in RA. METHODS: A literature search was conducted using PubMed, Cochrane Library, Embase, and trial registers to identify randomized controlled trials (RCTs) with a supervised land-based aerobic exercise program performed with an intensity between 50% and 90% of maximal heart rate, of at least 15 minutes' duration, performed at least 2 times a week, and lasting for a time period of at least 4 consecutive weeks. Risk of bias was assessed using the Cochrane tool. A meta-analysis of fatigue outcomes was performed by calculating the standardized mean difference (SMD) using a random-effects model. RESULTS: Five RCTs were included. None of the trials selected patients with RA for having fatigue. Risk of bias was low in 3 RCTs and unclear in 2. Land-based aerobic exercise programs had a positive effect on fatigue in RA compared to no exercise at 12 weeks, SMD -0.31 (95% confidence interval [95% CI] -0.55, -0.06). At 24 weeks, the effect of aerobic land-based exercise was smaller and not statistically significant: SMD -0.15 (95% CI -0.33, 0.02). CONCLUSION: There is evidence with low risk of bias that an aerobic exercise program is effective in reducing fatigue among patients with RA, especially in the short term; however, effects are small. To substantiate the evidence, RCTs should be performed in patients with RA selected for having fatigue.

Cost-effectiveness analysis of colorectal cancer treatments.

A concise overview is provided of the methodology of cost-effectiveness analyses, followed by a survey of published CEAs of colorectal cancer treatments. To gain credibility, the methodology applied in CEAs must be further improved. Costs are rarely estimated from the societal perspective, and little is known about how colorectal patients value their treatment and health.

The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.

PURPOSE: To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. PATIENTS: 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%). METHOD: Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated. RESULTS: On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule. CONCLUSION: The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial.

BACKGROUND: Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands. METHODS: A multistate Markov model was developed to simulate how patients' clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion. RESULTS: The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained. LIMITATIONS: A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results. CONCLUSIONS: Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.

Evidence-based diagnosis and clinical decision making.

The application of evidence-based dentistry to diagnosis should result in a reduction of errors in decision making. The frequency of errors is dependent not only on the accuracy of a diagnostic test for pathology, but also on the prior chance of disease being present. If this chance is low and below a certain threshold, then, for example, applying a diagnostic test can result in more decision errors and therefore inappropriate treatment than omitting to use the test. In deciding on the usefulness of a diagnostic test an additional factor to take into account is the relative value of the possible health states resulting from diagnosis and subsequent therapy. These can be determined by eliciting from the patient the numerical values of the possible dental health conditions using a visual analogue scale technique. Clinical decision analysis can then be carried out to calculate the most appropriate diagnostic strategy for the patient. Clinical decision analysis is starting to influence the development of guidelines for the diagnostic use of radiographs although its application in dentistry needs further refinement and development.