14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI).

BACKGROUND: The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED). METHODS: Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE. RESULTS: Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population. CONCLUSIONS: Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders. CLINICALTRIALS: Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

Implementing Technologies: Assessment of Telemedicine Experiments in the Paris Region: Reasons for Success or Failure of the Evaluations and of the Deployment of the Projects.

BACKGROUND: Telemedicine is increasingly viewed as a tool to provide a wide range of health services. This article presents policy lessons drawn from the evaluation of telemedicine experiments conducted in the Paris region. METHODS: We used a mixed method design to study telemedicine projects commissioned by the Paris Regional Health Agency between 2013 and 2017. We combined data analysis of the telemedicine projects, review of the protocols, and interviews with stakeholders. RESULTS: We identified the following reasons for disappointing outcomes: the outcome measure was requested too early during the experiments because payers required information for budgetary decisions; and the learning curve, technical problems, diversion of use, insufficient number of inclusions, and a lack of adherence prevented the demonstration of successful outcomes of the projects. CONCLUSION: The evaluation of telemedicine should be undertaken after sufficient uptake to ensure barriers to implementation are overcome, and to obtain the sample size necessary for statistical power and reduce the average cost for one telemedicine request. Randomized controlled trials should be encouraged with appropriate funding and the follow-up period should be extended.

Cost-effectiveness of 82-Rubidium PET myocardial perfusion imaging for the diagnosis of myocardial ischemia depending on the prevalence of coronary artery disease.

BACKGROUND: 82-Rubidium-Positron emission tomography myocardial perfusion imaging (Rb-PET-MPI) offers higher diagnostic performance for the detection of myocardial ischemia compared to Tc-SPECT-MPI. The aim of this economic evaluation was to perform a cost-effectiveness analysis of Rb-PET-MPI versus Tc-SPECT-MPI in patients with suspected myocardial ischemia according to pretest probabilities (PTP) of obstructive coronary artery disease based on the results of the RUBIS Trial. METHODS: Costs and effectiveness were calculated for all patients over 1 year and an incremental analysis of differences in costs and effectiveness in terms of diagnostic accuracy was performed. The uncertainty of the results was estimated using bootstrap. The analysis was conducted from the perspective of the French health care system with a time horizon of 12 months. RESULTS: The average cost of a Rb-PET-MPI-based strategy for the detection of myocardial ischemia was €219 lower than a SPECT-MPI-based strategy (€1192 (± 1834) vs €973 (± 1939), p < 0.01). The one-year incremental cost-effectiveness ratio was negative: - €2730 (money saved per additional accurate diagnosis) in patients presenting PTP > 15% for the Rb-PET-MPI vs. Tc-SPECT-MPI strategy. Analysis of the joint distribution of costs and outcomes found that the Rb-PET-MPI strategy had a 92% probability to be dominant (cost-saving and outcome-improving). CONCLUSIONS: Rb-PET-MPI is cost-effective compared to Tc-SPECT-MPI for the detection of myocardial ischemia in patients with PTP > 15% of obstructive coronary artery disease. TRIAL REGISTRATION: RUBIS Trial registration: NCT01679886, Registered 03 September 2012, https://clinicaltrials.gov/ct2/show/NCT01679886 .

Economic evaluation of restrictive vs. liberal transfusion strategy following acute myocardial infarction (REALITY): trial-based cost-effectiveness and cost-utility analyses.

AIMS: To estimate the cost-effectiveness and cost-utility ratios of a restrictive vs. liberal transfusion strategy in acute myocardial infarction (AMI) patients with anaemia. METHODS AND RESULTS: Patients (n = 666) with AMI and haemoglobin between 7-8 and 10 g/dL recruited in 35 hospitals in France and Spain were randomly assigned to a restrictive (n = 342) or a liberal (n = 324) transfusion strategy with 1-year prospective collection of resource utilization and quality of life using the EQ5D3L questionnaire. The economic evaluation was based on 648 patients from the per-protocol population. The outcomes were 30-day and 1-year cost-effectiveness, with major adverse cardiovascular events (MACEs) averted as the effectiveness outcome. and a 1-year cost-utility ratio.The 30-day incremental cost-effectiveness ratio was €33 065 saved per additional MACE averted with the restrictive vs. liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE-reducing (i.e. dominant). At 1 year, the point estimate of the cost-utility ratio was €191 500 saved per quality-adjusted life year gained; however, the cumulated MACE was outside the pre-specified non-inferiority margin, resulting in a decremental cost-effectiveness ratio with a point estimate of €72 000 saved per additional MACE with the restrictive strategy. CONCLUSION: In patients with AMI and anaemia, the restrictive transfusion strategy was dominant (cost-saving and outcome-improving) at 30 days. At 1 year, the restrictive strategy remained cost-saving, but clinical non-inferiority on MACE was no longer maintained. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02648113. ONE SENTENCE SUMMARY: The use of a restrictive transfusion strategy in patients with acute myocardial infarction is associated with lower healthcare costs, but more evidence is needed to ascertain its long-term clinical impact.

Effectiveness and cost-effectiveness of a telemedicine programme for preventing unplanned hospitalisations of older adults living in nursing homes: the GERONTACCESS cluster randomized clinical trial.

OBJECTIVE: The GERONTACCESS trial evaluated the utility and cost-effectiveness of a gerontological telemedicine (TLM) programme for preventing unplanned hospitalisation of residents living in nursing homes (NHs) in regions lacking medical facilities and/or qualified medical providers ("medical deserts"). DESIGN: GERONTACCESS was a 12-month, multicentre, prospective cluster-randomised trial conducted in NHs. The intervention group underwent TLM assessments every 3 months. The control group received the usual care. In both groups, comprehensive on-site assessments were conducted at baseline and the final visit. Care requirements were documented throughout the study. SETTING AND PARTICIPANTS: NH residents aged ≥ 60 years with multiple chronic diseases. METHODS: The study outcomes were the proportion of patients who experienced avoidable and unplanned hospitalisation, and the incremental cost savings per quality-adjusted life years from baseline to the 12-month follow-up. RESULTS: Of the 426 randomised participants (mean ± standard deviation age, 87.2 ± 7.6 years; 311 [73.0%] women), 23.4% in the intervention group and 32.5% in the control group experienced unplanned hospitalisation (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.43 to 0.97; p = 0.034). Each avoided hospitalisation in the intervention group saved $US 3,846. CONCLUSIONS AND IMPLICATIONS: The results of GERONTACCESS revealed that our gerontological, preventative TLM program significantly reduced unplanned hospitalisations. This innovative intervention limited disease progression and promoted a healthy lifestyle among NH residents. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02816177, registered June 28, 2016.

Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma.

PURPOSE: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma. METHODS: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs). FINDINGS: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses. IMPLICATIONS: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds.

Effectiveness and efficiency of tele-expertise for improving access to retinopathy screening among 351 neonates in a secondary care center: An observational, controlled before-after study.

In France, secondary care hospitals encounter difficulties to adhere to retinopathy of prematurity (ROP) screening guidelines. Our objective was to assess the effectiveness and efficacy of a tele-expertise program for ROP screening in neonatal intensive care units without on-site ophthalmologists. We evaluated the impact of a tele-expertise program funded by the Paris Region Health Authority in a secondary care center general hospital of the Paris Region (CHSF), where there was previously no on-site ophthalmologist. We performed an observational, controlled before-after study, with a university tertiary care center with on-site ophthalmologists (Port-Royal) as the control group. Recruitment and data collection for both periods took place from 1 January 2012 to 31 December 31 2012, and from 1 January 2014 to 31 March 2015. The primary endpoint was the percentage of compliance with screening guidelines, secondary endpoints included pain scores and costs. Over the two periods, at total of 351 infants were recruited in the CHSF. Implementation of the tele-expertise resulted in an absolute +57.3% increase in the proportion of examinations realized in accordance with guidelines (3.8% during the "before" period and 61.1% during the "after" period, p<0.001). As compared with the control group, the proportion of infants appropriately screened improved (57.5% versus 43.1%, p = 0.002); median pain score on the acute pain rating scale for neonates during examination was significantly higher (median score 5.5/10, range [2.5-5.7] versus 2.0/10, range [1.0-3.1], p = 0.002). Screening rates in the control group remained unchanged. The average cost per examination increased from €337 in the "before" period to €353 in the "after period" in the tele-expertise group. The implementation of tele-expertise for ROP screening in the CHSF medical center resulted in a major improvement of access to care with a small cost increase. The issue of pain control during examination with tele-expertise should be further addressed.