Manuela A. Joore

Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: A meta-analysis

PURPOSE To provide a comparison between radiotherapy with photons, protons and carbon-ions in the treatment of Non-Small-Cell Lung Cancer (NSCLC), performing a meta-analysis of observational studies. METHODS Eligible studies on conventional radiotherapy (CRT), stereotactic radiotherapy (SBRT), concurrent chemoradiation (CCR), proton therapy and carbon-ion therapy were searched through a systematic review. To obtain pooled estimates of 2- and 5-year disease-specific and overall survival and the occurrence of severe adverse events for each treatment modality, a random effects meta-analysis was carried out. Pooled estimates were corrected for effect modifiers. RESULTS Corrected pooled estimates for 2-year overall survival in stage I inoperable NSCLC ranged from 53% for CRT to 74% for carbon-ion therapy. Five-year overall survival for CRT (20%) was statistically significantly lower than that for SBRT (42%), proton therapy (40%) and carbon-ion therapy (42%). However, caution is warranted due to the limited number of patients and limited length of follow-up of the particle studies. CONCLUSION Survival rates for particle therapy were higher than those for CRT, but similar to SBRT in stage I inoperable NSCLC. Particle therapy may be more beneficial in stage III NSCLC, especially in reducing adverse events.

Specialised treatment based on cognitive behaviour therapy versus usual care for tinnitus: a randomised controlled trial

BACKGROUND Up to 21% of adults will develop tinnitus, which is one of the most distressing and debilitating audiological problems. The absence of medical cures and standardised practice can lead to costly and prolonged treatment. We aimed to assess effectiveness of a stepped-care approach, based on cognitive behaviour therapy, compared with usual care in patients with varying tinnitus severity. METHODS In this randomised controlled trial, undertaken at the Adelante Department of Audiology and Communication (Hoensbroek, Netherlands), we enrolled previously untreated Dutch speakers (aged >18 years) who had a primary complaint of tinnitus but no health issues precluding participation. An independent research assistant randomly allocated patients by use of a computer-generated allocation sequence in a 1:1 ratio, stratified by tinnitus severity and hearing ability, in block sizes of four to receive specialised care of cognitive behaviour therapy with sound-focused tinnitus retraining therapy or usual care. Patients and assessors were masked to treatment assignment. Primary outcomes were health-related quality of life (assessed by the health utilities index score), tinnitus severity (tinnitus questionnaire score), and tinnitus impairment (tinnitus handicap inventory score), which were assessed before treatment and at 3 months, 8 months, and 12 months after randomisation. We used multilevel mixed regression analyses to assess outcomes in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00733044. FINDINGS Between September, 2007 and January, 2011, we enrolled and treated 492 (66%) of 741 screened patients. Compared with 247 patients assigned to usual care, 245 patients assigned to specialised care improved in health-related quality of life during a period of 12 months (between-group difference 0·059, 95% CI 0·025 to 0·094; effect size of Cohens d=0·24; p=0·0009), and had decreased tinnitus severity (-8·062, -10·829 to -5·295; d=0·43; p<0·0001) and tinnitus impairment (-7·506, -10·661 to -4·352; d=0·45; p<0·0001). Treatment seemed effective irrespective of initial tinnitus severity, and we noted no adverse events in this trial. INTERPRETATION Specialised treatment of tinnitus based on cognitive behaviour therapy could be suitable for widespread implementation for patients with tinnitus of varying severity. FUNDING Netherlands Organisation for Health Research and Development (ZonMW).

Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial.

It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs (

How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons

3222 versus

Joint recovery programme versus usual care : An economic evaluation of a clinical pathway for joint replacement surgery

4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis

PURPOSE Particle therapy has potentially a better therapeutic ratio than photon therapy. However, investment costs are much higher. This study provides an estimation and comparison of the costs of these therapies. METHODS Within an extensive analytical framework capital and operational costs, cost per fraction, and four tumor specific treatment costs are calculated for three facilities: combined carbon-ion/proton, proton-only, and photon. RESULTS Capital costs for the combined, proton-only and photon facilities are: euro 138.6 million, euro 94.9 million, euro 23.4 million. Total costs per year are: euro 36.7 million, euro 24.9 million, euro 9.6 million. Cost per fraction is: euro 1128 (euro 877-1974), euro 743 (euro 578-1300), euro 233 (euro 190-407). Cost ratio particle/photon therapy is 4.8 for the combined and 3.2 for the proton-only facility. Particle treatment costs vary from euro 10,030 (c-ion: lung cancer) to euro 39,610 (proton: head & neck tumors). Cost difference between particle and photon therapies is relatively small for lung and prostate cancer, larger for skull-base chordoma and head & neck tumors. CONCLUSION Investment costs are highest for the combined carbon-ion/proton facility and lowest for the photon facility. Cost differences become smaller when total costs per year and specific treatment costs are compared. Lower fractionation schedule of particle therapy might further reduce its costs.

Safely Ruling Out Deep Venous Thrombosis in Primary Care

Objective:The objective of the present study was to determine the incremental cost-effectiveness of a clinical pathway for patients undergoing joint replacement, the Joint Recovery Programme (JRP), as compared with usual care. The existing care process was revised to contain costs and shorten waiting lists by facilitating patient flows and improve healthcare efficiency. Methods:The study design was a before–after trial. In total, 160 patients undergoing total hip and total knee replacement, aged 28 to 87 years (mean age, 64.4 years), were treated either according to the Joint Recovery Programme (a standardized care process with patient education and rehabilitation in groups) or usual care. Both groups were followed for 1 year. Costs were studied from a societal perspective. Outcomes included functional level (Harris Hip score and American Knee Society score) and generic quality of life (EuroQol). Results:The results indicate that the Joint Recovery Programme resulted in a significant cost saving when compared with usual care mainly as a result of a considerable (>50%) reduction in length of hospital stay. The average cost saving per patient amounted to

Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer

1261 in the total hip replacement group and

Literature review on monitoring technologies and their outcomes in independently living elderly people

3336 in the total knee replacement group. At the same time, both functional level and quality of life were higher in the JRP group. Conclusions:Clinical pathway dominates usual care and is a highly cost-effective approach to contain costs related to joint replacement surgery without adverse consequences for patients.

Systematic review and meta-analysis of radiotherapy in various head and neck cancers: Comparing photons, carbon-ions and protons

BACKGROUND Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain. METHODS Sixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used. RESULTS Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR-) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of < 20% can be used to rule out an AMI (LR- 0.04, 95% CI 0.02 to 0.10). The optimum strategy, based on the Abbott assay, used a limit of detection (LoD) threshold in a presentation sample to rule out AMI (LR- 0.01, 95% CI 0.00 to 0.08). Patients testing positive could then have a further test at 3 hours; a result above the 99th centile on this sample has some potential for ruling in an AMI (LR+ 10.16, 95% CI 8.38 to 12.31), whereas a result below the 99th centile can be used to rule out an AMI (LR- 0.02, 95% CI 0.01 to 0.05). In the base-case analysis, standard Tn testing was both most effective and most costly. Strategies considered cost-effective depending upon incremental cost-effectiveness ratio thresholds were Abbott 99th centile (thresholds of < £6597), Beckman 99th centile (thresholds between £6597 and £30,042), Abbott optimal strategy (LoD threshold at presentation, followed by 99th centile threshold at 3 hours) (thresholds between £30,042 and £103,194) and the standard Tn test (thresholds over £103,194). The Roche 99th centile and the Roche optimal strategy [LoB threshold at presentation followed by 99th centile threshold and/or Δ20% (compared with presentation test) at 1-3 hours] were extendedly dominated in this analysis. CONCLUSIONS There is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI. Further research is needed to clarify optimal diagnostic thresholds and testing strategies. STUDY REGISTRATION This study is registered as PROSPERO CRD42013005939. FUNDING The National Institute for Health Research Health Technology Assessment programme.