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 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 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.

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.

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).

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.

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.

[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.

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.

Long-term followup of health status in patients with severe rheumatoid arthritis after high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation.

OBJECTIVE: High-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe, refractory rheumatoid arthritis (RA). The present study was undertaken to assess the health status of patients with severe RA over a long-term followup period after treatment with HDC + HSCT. METHODS: Health status and utility scores were assessed in 8 patients before and after treatment with HDC + HSCT. Patients were followed up for 5 years posttransplantation. Health status was assessed by the Health Assessment Questionnaire (HAQ), the RAND-36 version of the Short Form 36 (SF-36) health survey, and the Arthritis Impact Measurement Scales (AIMS). Utility scores were calculated using the EuroQol (EQ-5D) questionnaire and the SF-36-derived utility index (called the SF-6D), from which quality-adjusted life years (QALYs) were derived. RESULTS: Most measures of health status improved compared with baseline in the first 2 years posttransplantation, notably HAQ and AIMS scores and scores on the functional status, general health, and health change summary scales of the RAND-36 version of the SF-36. Utility scores derived from the EQ-5D questionnaire and the SF-6D also increased significantly after transplantation. This was reflected in the 0.28 QALYs gained compared with baseline. For a putative 50-year-old RA patient with a life expectancy of 20 years, a threshold analysis revealed that HDC + HSCT yielded more QALYs than conventional therapy when treatment-related mortality (TRM) was <2.8%. CONCLUSION: HDC + HSCT temporarily increased the functionality and health status of patients with severe, refractory RA. With a reported TRM of 1.3%, HDC + HSCT can be considered a realistic treatment option for patients with severe RA.

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.