Lars Oddershede

The effect of radiotherapy beam energy on modern cardiac devices: an in vitro study.

AIMS Radiotherapy (RT) for malignancies can harm pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). There is some evidence that, besides cumulative dose, the damaging radiation effects increase with beam energy. The aim of this study was to determine whether modern PMs and ICDs are more sensitive to high-energy than to low-energy photon beams. METHODS AND RESULTS Two groups of unused PMs and explanted ICDs (five PMs and one ICD in each) were subjected to irradiations in a phantom with 6 and 18 megavolt (MV) photons, respectively. The devices were exposed to radiation at doses of 2 gray (Gy) daily to simulate two clinical scenarios with the PM/ICD in the RT field. A cumulative dose of 150 Gy was given to each device, corresponding to approximately twice the therapeutic dose. In the 6 MV group, one episode of PM malfunction was detected after reaching 150 Gy. In the 18 MV group, a total of 14 episodes of malfunction were detected starting at 30 Gy in all five PMs. No episodes appeared in the ICD, at the respective treatment groups. This corresponded to a hazard ratio of 9.11 [∼95% confidence interval (CI): 1.04-79.69] by Cox regression analysis between the two groups. In a repeated measures logistic regression model comparing the incidence rate of malfunctions, the odds ratio was 18.29 (∼95% CI: 1.52-219.41). CONCLUSION Photon beam energy plays a considerable role in inducing implantable cardiac device malfunctions. Low-energy RT may be safer in PM/ICD patients despite relatively high radiation dose to the device.

Economic Evaluation of Endoscopic Versus Open Vein Harvest for Coronary Artery Bypass Grafting

BACKGROUND A short saphenous vein segment is commonly used as a conduit for coronary artery bypass grafting, and clinicians must decide whether to obtain it by performing open (OVH) or endoscopic vein harvest (EVH). We conducted a health economic evaluation, using data on resource usage collected alongside a randomized controlled trial, to investigate whether EVH is cost-effective compared with OVH. METHODS Analyses were performed in accordance with international guidelines for health economic evaluations. We constructed 3 cost-levels as the current literature is inconclusive as to which resource consumptions differ significantly between harvesting methods. Outcomes were measured as purulent infections avoided in the cost-effectiveness analysis and for the cost-utility analysis we estimated quality-adjusted life-years gained. Results were presented as incremental cost-effectiveness ratios: ie, the extra cost of obtaining one extra quality-adjusted life-year and the extra cost of avoiding one purulent infection. To handle uncertainties, we performed bias corrected bootstrap analyses on 5,000 resamples and constructed cost-effectiveness acceptability curves. RESULTS The incremental cost-effectiveness ratio was

Estimation of utility values from visual analog scale measures of health in patients undergoing cardiac surgery

79,391/quality-adjusted life-year and

Decreased patency rates following endoscopic vein harvest in coronary artery bypass surgery

1,970/purulent infection avoided when costs and outcomes within 35 days postoperatively were compared. Within 35 days postoperatively, EVH was less than 1% cost-effective at a willingness-to-pay threshold of

The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

50,000/quality-adjusted life-year. CONCLUSIONS The EVH was not cost-effective within 35 days postoperatively. Future studies should investigate long-term cost effectiveness.

Endoscopic vein harvesting for coronary artery bypass grafting is safe and reduces postoperative resource consumption

Introduction In health economic evaluations, mapping can be used to estimate utility values from other health outcomes in order to calculate quality adjusted life-years. Currently, no methods exist to map visual analog scale (VAS) scores to utility values. This study aimed to develop and propose a statistical algorithm for mapping five dimensions of health, measured on VASs, to utility scores in patients suffering from cardiovascular disease. Methods Patients undergoing coronary artery bypass grafting at Aalborg University Hospital in Denmark were asked to score their health using the five VAS items (mobility, self-care, ability to perform usual activities, pain, and presence of anxiety or depression) and the EuroQol 5 Dimensions questionnaire. Regression analysis was used to estimate four mapping models from patients’ age, sex, and the self-reported VAS scores. Prediction errors were compared between mapping models and on subsets of the observed utility scores. Agreement between predicted and observed values was assessed using Bland–Altman plots. Results Random effects generalized least squares (GLS) regression yielded the best results when quadratic terms of VAS scores were included. Mapping models fitted using the Tobit model and censored least absolute deviation regression did not appear superior to GLS regression. The mapping models were able to explain approximately 63%–65% of the variation in the observed utility scores. The mean absolute error of predictions increased as the observed utility values decreased. Conclusion We concluded that it was possible to predict utility scores from VAS scores of the five dimensions of health used in the EuroQol questionnaires. However, the use of the mapping model may be inappropriate in more severe conditions.

Health economic evaluation of single-lead atrial pacing vs. dual-chamber pacing in sick sinus syndrome

Abstract Objectives. Endoscopic vein harvest has gained widespread use in coronary artery bypass surgery. However, potential negative mid- and long-term effects following endoscopic vein harvest have been described. We aimed to compare long-term clinical outcomes following endoscopic and open vein graft harvesting. Design. This study was a clinical follow-up with additional computed tomographic coronary angiography among 126 first-time bypass patients originally included in a randomized study comparing early leg wound complications and cosmetic results. Deceased patients were retrospectively followed up. Results. Follow-up was complete, but information on clinical endpoints was not available in all patients. A total of 111 patients were alive at follow-up. Median observation time was 6.3 (range: 0.2–9.1) years including three in-hospital deaths. Vein graft failure was significantly higher in the endoscopic vein harvest (EVH) group (13 of 31; 42%) compared with the open vein harvest (OVH) group (2 of 32, 6%) (P = 0.001). However, this difference was not reflected by differences in recurrence of angina (P = 0.44), myocardial infarction (P = 0.11), and all-cause mortality (P = 0.15). Conclusions. Using a median follow-up time of 6.3 years significantly more vein graft failures were identified following EVH compared with OVH without any differences in long-term clinical outcomes. Trial registration: ClinicalTrials.gov identifier: NCT01480726.

The cost-effectiveness of venous-converted acid-base and blood gas status in pulmonary medical departments

BACKGROUND Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain. OBJECTIVE To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial. DESIGN Open-label, parallel-group, randomised controlled trial. SETTING Forty-three HIV clinical centres in the UK NHS. PARTICIPANTS HIV-positive adults taking standard combination ART with a suppressed VL for ≥ 6 months. INTERVENTIONS Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound. MAIN OUTCOME MEASURES The primary outcome was reduction of future drug options, defined as new intermediate-/high-level resistance to one or more drugs to which the patients virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis. RESULTS In total, 587 participants were randomised (77% male, 68% white) to OT (n = 291) or PI-mono (n = 296) and followed for a median of 44 months, of whom 2.7% withdrew/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan-Meier estimate 3.2%) in the OT group and 95 patients (35.0%) in the PI-mono group [absolute risk difference 31.8%, 95% confidence interval (CI) 24.6% to 39.0%; p < 0.001]. PI-mono patients who changed to ART after VL rebound all resuppressed (median 3.5 weeks). The proportions with loss of a future drug option at 3 years were 0.7% in the OT group and 2.1% in the PI-mono group (difference 1.4%, (95% CI -0.4% to 3.4%); non-inferiority demonstrated). There were no significant differences in serious disease complications between groups or in the frequency of grade 3 or 4 clinical AEs (16.8% OT group vs. 22% PI-mono group; absolute risk difference 5.1%, 95% CI -1.3% to 11.5%; p = 0.12). Overall, the PI-mono strategy was shown to be cost-effective compared with OT under most scenarios explored. PI-mono was cost saving because of the large savings in ART drug costs while being no less effective in terms of quality-adjusted life-years in the within-trial analysis and only marginally less effective when extrapolated to lifetime outcomes. CONCLUSIONS PI monotherapy, with prompt reintroduction of combination therapy for VL rebound, was non-inferior to combination therapy in preserving future treatment options and is an acceptable and cost-effective alternative for long-term management of HIV infection. TRIAL REGISTRATION Current Controlled Trials ISRCTN04857074. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 21. See the NIHR Journals Library website for further project information.

Is the accuracy of preoperative MRI stage in rectal adenocarcinoma influenced by tumour height

Background: The greater saphenous vein is still frequently used as a conduit for coronary artery bypass grafting (CABG). Previously, veins were harvested through a single continuous skin incision, commonly referred to as open vein harvesting (OVH), while endoscopic vein harvesting (EVH) techniques have become increasingly popular. However, the postoperative consumption of healthcare resources remains uncertain. Therefore, the present study performed a systematic review, with meta-analysis, of outcomes relating to consumption of healthcare resources and clinical effectiveness following EVH and OVH for CABG. Methods: A systematic search was performed in five databases. OVH was defined as the use of open harvesting techniques using a single continuous incision, and all studies comparing EVH to OVH for CABG were eligible. Results: EVH was associated with increased duration of surgery, no difference in the length of stay in intensive care units, a reduced total length of stay in hospital, a reduced need for antibiotic treatment for leg wound infections, a reduced need for follow-up visit(s) at general practitioners/out-patient clinics, a reduced need for visit(s) by the homecare nurses, a reduced need for revision(s) of the leg wound, a reduced need for readmission(s) related to leg wounds complications and no difference in repeat cardiac catheterization(s). Furthermore, EVH reduced pain intensity approximately five days postoperatively, but not 30 days postoperatively. EVH did not increase the occurrence of mid-term myocardial infarction, recurrence of chest pain, repeat revascularization and mid-term allcause mortality. Conclusions: EVH provides safe clinical outcomes compared to OVH while reducing the short-term postoperative resource consumption. This article provides a formal synthesis of the available data on clinical effectiveness and consumption of healthcare resources following EVH and OVH for CABG, hence enabling future investigation of the long-term cost-effectiveness of methods.

Adjustment of foreign EQ-5D-3L utilities can increase their transferability

AIMS The recent Danish Multicentre Randomized Trial on Single-Lead Atrial (AAIR) Pacing versus Dual-Chamber (DDDR) Pacing in Sick Sinus Syndrome (DANPACE) suggested DDDR pacing as standard care. However, previous findings supported the routine use of AAIR pacing. This study investigated the cost-effectiveness of DDDR pacing compared with AAIR pacing for sick sinus syndrome. METHODS AND RESULTS A decision-analytical model based on patient-level data from three randomized trials was designed from the Danish healthcare systems perspective. The main outcomes were lifetime costs, quality-adjusted lifeyears (QALYs), and net monetary benefit. Quality-adjusted lifeyears were calculated by utilizing community-based preferences. Costs were calculated by utilizing the extensive data on resource consumption, from the DANPACE trial. Data were pooled and adjusted for baseline differences. Dual-chamber pacing was shown to be cost-effective in all the analyses using a willingness-to-pay (WTP) threshold of £20,000/QALY, and most analyses using a WTP of £30,000/QALY. When pooling the data and adjusting for baseline differences, Monte Carlo simulations revealed a 51-71% probability of DDDR pacing being cost-effective at a WTP of £20,000/QALY, and a 42-58% probability at a WTP of £30,000/QALY. Dual-chamber pacing was most likely to be cost-effective among elderly patients with comorbidity. The expected value of perfect information was low and initiation of additional publicly funded Danish trials was discouraged. CONCLUSION Dual-chamber pacing is likely to be a cost-effective treatment for sick sinus syndrome patients.