Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC-screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1-4, the initiation of IFN-free regardless of fibrosis was a cost-effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400-88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2-3, the most cost-effective strategy was IFN-based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN-free regimens being more effective but not cost-effective at current costs. The budget impact of treating all CHC-screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2-3 with IFN-based or IFN-free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost-effective, but would add 3.5-7.2 billion € to an already overburdened medical care system.

Prospective assessment of rapid diagnostic tests for the detection of antibodies to hepatitis C virus, a tool for improving access to care.

Large-scale hepatitis C screening is required to prevent further spread of the infection, improve access to care in the context of new hepatitis C virus (HCV) drug regimens without interferon-alpha and subsequently reduce the risk of long-term complications of chronic liver disease. Rapid diagnostic tests (RDTs) represent an attractive alternative to enzyme immunoassay using blood from venepuncture. The aim of the present study was to prospectively assess the clinical performance of CE-marked RDTs detecting anti-HCV antibodies in fingerstick capillary whole blood and/or oral fluid. A total of 513 individuals, including 318 patients with chronic HCV infection, 25 patients with resolved HCV infection and 170 HCV-seronegative individuals, were prospectively enrolled. The specificity of RDTs with fingerstick whole blood varied from 98.8% to 100%. The clinical sensitivity was high for the OraQuick(®) and Toyo(®) tests (99.4% and 95.8%, respectively), but low for the Labmen(®) test (63.1%). The specificity and clinical sensitivity in crevicular fluid were both satisfactory for the OraQuick(®) test (100% and 97.6%, respectively). HCV antibody RDTs were easy and rapid to perform in the context of patient care. They were highly specific. Both the OraQuick(®) and Toyo(®) tests reached the expected level of performance for wide-scale use, with a performance advantage for the OraQuick(®) HCV test. RDTs appear to be a promising new tool for wide-scale screening of HCV infection in high-risk to medium-risk populations. Hence, careful assessment of the performance of HCV RDTs must be recommended before they can be implemented in clinical practice.

Effects 4.5 years after an interactive GP educational seminar on antibiotic therapy for respiratory tract infections: a randomized controlled trial.

BACKGROUND: The few studies assessing long-term effects of educational interventions on antibiotic prescription have produced conflicting results. OBJECTIVES: Our aim was to assess the effects after 4.5 years of an interactive educational seminar designed for GPs and focused on antibiotic therapy in respiratory tract infections (RTIs). The seminar was expected to decrease antibiotic prescriptions for any diagnosis. METHODS: We conducted a randomized controlled parallel-group trial in a Paris suburb (France), with GPs as the randomization unit and prescriptions as the analysis unit. The intervention occurred in September 2004 and the final assessment in March 2009. Among 203 randomized GPs, 168 completed the study, 70 in the intervention group and 98 in the control group. Intervention GPs were randomized to attending only a 2-day interactive educational seminar on evidence-based guidelines about managing RTIs or also 1 day of problem-solving training. The primary outcome was the percentage of change in the proportion of prescriptions containing an antibiotic for any diagnosis in 2009 versus 2004. An intention-to-treat sensitivity analysis was performed using multiple imputation. RESULTS: After 4.5 years, absolute changes in the primary outcome measure were -1.1% (95% confidence interval: -2.2 to 0.0) in the intervention group and +1.4% (0.3-2.6) in the control group, yielding an adjusted between-group difference of -2.2% (-2.7 to -1.7; P < 0.001). Both intervention modalities had significant effects, and multiple imputation produced similar results. CONCLUSIONS: A single, standardized and interactive educational seminar targeting GPs significantly decreased antibiotic use for RTIs after 4.5 years.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Assessment of calf muscle contraction by diffusion tensor imaging.

The goal of this study was to assess the changes of water diffusion during contraction and elongation of calf muscles using diffusion tensor (DT) MRI in normal volunteers. Twenty volunteers (mean age, 29+/-4 years) underwent DT MRI examination of the right calf. Echo planar imaging sequence was performed at rest, during dorsal flexion and during plantar flexion. The three eigenvalues (lambda1, lambda2, and lambda3), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the diffusion tensor were calculated for medial gastrocnemius (mGM) and tibialis anterior (TA). A fiber tractography was performed on both muscles. Non-parametric Wilcoxon and Mann Whitney tests were used for statistical evaluation. At rest, lambda1, lambda2 and ADC of mGM were higher than their counterparts of TA (P<0.01). During dorsal flexion, the three eigenvalues and ADC of TA significantly increased (P<0.05) as their counterparts of mGM slightly decreased (P=NS). Opposite variations were detected during plantar flexion of the foot. Visual analysis evidenced a relationship between 3D representations of MRI fibers and physiological state of muscles. Contraction of calf muscles produces changes in DT parameters, which are related to the physiological state of the muscle.

Abdominal aortic aneurysm sac behavior following Cook Zenith graft implantation: a five-year follow-up assessment of 212 cases.

AIM: Aneurysm shrinkage is an expected outcome after stent-grafting for abdominal aortic aneurysm (AAA). A worrying problem following repair is progressive enlargement indicating persistent sac pressurization: in this setting not all grafts are equal. The Cook Zenith device (CZ) became available on the European market in 1999. While multicenter studies on the device have shown favorable clinical results at mid-term follow-up, few have focused on sac behavior. This study evaluated AAA sac behavior and predictive factors of its evolution by assessing the five-year results obtained with the CZ graft in a single-institution experience. METHODS: All consecutive elective surgery patients treated with a CZ graft for infrarenal aortic or aortoiliac aneurysm repair from January 2000 to November 2004 in our institution were included prospectively in the study and followed at 1, 6, 12, 18, 24 months and yearly thereafter. Pre-, intra- and postoperative data were recorded in a computerized database. Computed tomography (CT) scans were reviewed by a senior radiologist to identify any abnormalities including endoleak and graft malfunction. Pre- and postoperative maximum sac diameters were derived from measurements of CT findings and then compared. A change of at least 8 mm in sac size was considered significant. Overall results are expressed according to the Committee on Reporting Standards of AAA treatment. Factors that may have influenced sac behavior were analyzed by dividing the patients into 3 groups according to whether the sac diameter remained unchanged (group 1), had increased (group 2) or regressed (group 3). Statistical analysis of the demographic and CT-scan data was then performed. RESULTS: The study sample was 212 consecutive patients (mean age 72.8+/-9.0 years); the mean aneurysm diameter before treatment was 55.5+/-9.8 mm. All stent grafts were successfully implanted. The 30-day mortality rate was 0.94% (2/212); the morbidity rate was 11.7% (25/212). The primary technical success rate was 93.40%; the assisted primary technical success and secondary technical success rates were 96.63% and 99.52%, respectively. The mean follow-up period was 17.7+/-14.7 (1-60) months. The cumulative survival probability was 94%, 84.2%, and 72.9% at 12, 24, and 36 months, respectively. The endoleak-free survival probabilities at 12 and 24 months were 75.7% and 62.8%, respectively. The free of intervention survival rates were 82.1%, 68.9% and 60.6% at 12, 24 and 38 months, respectively. At five years follow-up, the overall clinical success rate was 49.5%. If changes in sac diameter occurred, they were noted at 13 months on average. Sac size remained unchanged in 115 (54.3%) patients (group 1), increased in 9 (4.2%) (group 2), and regressed in 88 (41.5%) (group 3). Neither preoperative patient demographics nor aneurysm characteristics were found to be predictive of sac behavior. Aortouniliac graft configuration was predictive of sac shrinkage (P=0.020). Endoleak was more frequent among patients in groups 1 (27/115; 23%) and 2 (5/9; 56%) than among those in group 3 (9/88;10%) (P=0.001). Reduction in aneurysm sac diameter was less marked in patients with any type of endoleak (P=0.0003). CONCLUSION: The CZ grafts offered satisfactory overall results up to five years of follow-up; nevertheless, sac diameter increased in 4.25% of patients. Endoleak was a predictive factor of a lack of sac shrinkage, while aortouniliac graft configuration was predictive of sac shrinkage.

[Hepavir, the first observational study of one cohort of patients treated with alpha-2a interferon, monotherapy. Evaluation of asthenia and its social consequences]. / Hépavir, première étude observationnelle d'une cohorte de malades traités par interféron alpha-2a en monothérapie. Evaluation de l'asthénie et de ses répercussions sociales.

OBJECTIVES: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue. METHODS: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness. RESULTS: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment. CONCLUSION: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Costs and benefits of measures to prevent needlestick injuries in a university hospital.

OBJECTIVE: To document the costs and the benefits (both in terms of costs averted and of injuries averted) of education sessions and replacement of phlebotomy devices to ensure that needle recapping did not take place. DESIGN: The percentage of recapped needles and the rate of needlestick injuries were evaluated in 1990 and 1997, from a survey of transparent rigid containers in the wards and at the bedside and from a prospective register of all injuries in the workplace. Costs were computed from the viewpoint of the hospital. Positive costs were those of education and purchase of safer phlebotomy devices; negative costs were the prophylactic treatments and follow-up averted by the reduction in injuries. SETTING: A 1,050-bed tertiary-care university hospital in the Paris region. RESULTS: Between the two periods, the proportion of needles seen in the containers that had been recapped was reduced from 10% to 2%. In 1990, 127 needlestick (12.7/100,000 needles) and 52 recapping injuries were reported versus 62 (6.4/100,000 needles) and 22 in 1996 and 1997. When the rates were related to the actual number of patients, the reduction was 76 injuries per year. The total cost of information and preventive measures was $325,927 per year. The cost-effectiveness was $4,000 per injury prevented. CONCLUSION: Although preventive measures taken to ensure reduction of needlestick injuries appear to have been effective (75% reduction in recapping and 50% reduction in injuries), the cost of the safety program was high.

Reducing unnecessary laboratory use with new test request form: example of tumour markers.

To limit the ordering of serum tumour marker tests that are clinically irrelevant, we designed a new request form. This is a matrix of boxes, rows being individual markers and columns body organs. The box at the intersection of line and column is colour-coded to indicate whether the test is appropriate or not. These ratings were allocated on the basis of published data and local consensus. This new form replaced the form in use at our hospital at the beginning of 1992, and resulted in a 25% decrease in the ordering of tumour markers. Adapting the design of the test request form is a low-cost intervention that combines both economic and clinical requirements in reducing the prescription of tests that are useless in a given clinical situation.