Cost-effectiveness analysis of patent foramen ovale closure with Amplatzer plus medical therapy compared to medical therapy in patients with a history of stroke in France.

BACKGROUND: A patent foramen ovale (PFO) is formed when the ovale foramen does not close spontaneously or re-opens leaving the right and left atrium connected. The present study was conducted to analyze the cost-effectiveness of PFO closure with Amplatzer device plus medical therapy (MT) compared to MT alone in the French reimbursement system for PFO patients with a prior history of stroke, using the RESPECT study data. METHODS: A multi-state Markov model was used. The analysis was conducted from a collective perspective over a 10-year time horizon with 4% discount applied for costs and health effects. The simulated population included adult patients with PFO. Sub-group analysis was limited to patients with atrial septal aneurysm and/or a large-shunt. Clinical inputs were derived from the RESPECT study and literature. Costs associated with the device, drugs, and management were sourced from literature and national databases. The outcomes of analyses included life-years (LYs), quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and number of recurrent strokes avoided. Scenario and sensitivity analyses were conducted to assess the robustness of the results. RESULTS: The use of Amplatzer plus MT provided additional QALYs (0.16) at an incremental cost of 7301€, generating an ICER of 46,288€/QALY for Amplatzer vs. MT alone. In the sub-group analysis, Amplatzer plus MT provided additional QALYs (0.20) at an incremental cost of 5818€, generating an ICER of 28,624€/QALY for Amplatzer plus MT vs. MT alone. Amplatzer plus MT led to lower number of recurrent strokes in comparison to MT alone in both populations. Scenario and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Amplatzer plus MT represents a cost-effective treatment option and is associated with lower stroke recurrence compared to MT alone for PFO patients with a prior history of stroke.

Relationship Between Chronic Lateral Ankle Instability and Hindfoot Varus Using Weight-Bearing Cone Beam Computed Tomography.

BACKGROUND: Varus hindfoot deformity may increase the risk of chronic lateral ankle instability (CLAI). Our aim was to analyze hindfoot alignment (HFA) in patients with CLAI using weight-bearing cone beam computed tomography (WBCT) to assess this risk. METHODS: This retrospective, comparative analysis was carried out using an existing WBCT database (Talas, CurveBeam LLC), including data sets for 370 consecutive feet (189 patients) obtained between July 2016 and October 2018 at a single institution. The software provided semiautomated measurement of HFA, given as foot ankle offset (FAO). Univariate analysis was conducted to compare feet with and without CLAI against sex, age, body mass index, and FAO. Significant variables were included in a multivariable logistic model with random effects to take into account correlation between feet of the same patient. RESULTS: Forty-three feet had CLAI (34 patients). FAO (P = .0009) was significant for CLAI by univariate analysis. Mean FAO was -2.2% ± 5.5% (varus) and + 2.6% ± 4.7% (valgus) with and without CLAI history, respectively. Multivariable logistic regression adjusted for sex and age demonstrated a 35% increased odds ratio (OR) of CLAI per 1% reduction in FAO value (varus) (adjusted OR=0.64, 95% confidence interval [CI]: 0.49-0.84; P = .001) and no significant effect of sex (adjusted OR=0.52; P = .617) or age (adjusted OR=0.94; P = .165) after adjustment for FAO. CONCLUSION: A positive relationship was found between varus HFA and the risk to have CLAI. Systematic recording of FAO measurements from WBCT images along with clinical data regarding CLAI history proved successful at quantifying the risk of CLAI. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis.

BACKGROUND: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far. OBJECTIVE: To compare CPM to methylprednisolone (MP) in SPMS. METHODS: Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area-MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model. RESULTS: Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31-1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14-4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17-0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected. CONCLUSION: Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability. TRIAL REGISTRATION: Clinicaltrials.gov NCT00241254.

Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention.

OBJECTIVE: To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. METHODS: A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. CONCLUSIONS: Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations.

Metabolic imbalance of the insulin-like growth factor-I axis in Zucker diabetic fatty rats.

In healthy conditions, insulin-like growth factor-I (IGF-I) acts in a coordinated fashion with insulin to lower glycemia, mainly by increasing insulin sensitivity in peripheral tissues. The aim of this study was to explore the relationship between glucose homeostasis and the endocrine IGF-I axis in Zucker diabetic fatty (ZDF) rats. The plasma levels of glucose, insulin, growth hormone, free IGF-I, total IGF-I (associated to insulin-like growth factor binding proteins plus free), and corticosterone were measured in 13-week-old ZDF rats and in age-matched controls under fasting and postprandial conditions. The plasma IGF-I binding capacity was measured by radioligand binding. In ZDF rats, fasting total and free IGF-I levels were reduced by 22% and 92%, respectively, compared with controls. Postprandial free IGF-I was reduced by 35%, whereas total IGF-I was unaffected. The plasma IGF-I binding capacity in ZDF rats was reduced by 24% after fasting and by 13% under postprandial conditions. A clear correlation between free IGF-I and insulin was observed in postprandial controls but not in ZDF rats. A principal component analysis clearly separated ZDF and control rats into 2 main components under both fasting and postprandial conditions. The first component was determined equally by total IGF-I, bound IGF-I, the free to total IGF-I ratio, and the IGF-I binding capacity. The second component was determined mostly by glucose and insulin. Our results show a marked alteration of the plasma IGF-I levels and of the capacity of plasma to bind IGF-I, and a disturbed relationship between IGF-I and postprandial insulinemia in a rat model of type 2 diabetes mellitus.