Risk management in transfusion after the HIV blood contamination crisis in France: the impact of the precautionary principle.

The importance of the precautionary principle in public health was highlighted in France after the HIV contamination of blood products used for transfusion. However, the definition of this principle, its objectives, the way in which it should be applied, and its consequences had not been considered previously. The question as to whether the application of the precautionary principle is appropriate remains unanswered. The aim of this study was to analyze the interpretations of the application of the precautionary principle to determine its consequences in terms of risk management and patient rights. This was accomplished by interviewing persons involved in transfusion medicine. We conducted 33 interviews and describe the issues enunciated for and against the application of the precautionary principle. The precautionary principle concept was confusing to the respondents. A major issue emerging from the interviews was that the precautionary principle was perceived more as a means of protecting the decision maker than as a means of protecting the patient. Taken to its extreme, the use of the precautionary principle could prejudice sound medical decision making. However, it was felt that it also can lead to the introduction of measures that update and gradually reduce risks associated with transfusion

[The precautionary principle applied to blood transfusion. What is its impact on practices and risk management?]

The precautionary principle has boomed in the French public health sector through blood transfusion. There has been, however, no perambulatory reflection on the definition, objectives, methods of application or consequences of this principle. The question of the pertinence of its application remains unanswered. This study, based on interviews with blood transfusion practitioners, aims to establish their perceptions of the precautionary principle's application in this specific field and of its consequences in terms of risk management and patients' rights. The pros and cons of this application are analysed based on these perceptions. According to our analysis, the precautionary principle seems to be born of confusion. It is seen more as a way to protect decision makers than patients and, if taken to extremes, could prejudice medical logic. Nevertheless, it also brings measures which renew and encourage evolution in transfusion risk management

[Informing the transfused patient of the possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion]

TRUE RISKS AND THEORETICAL RISKS: The texts ruling the obligation of the physician to inform the patient appears not to include theoretical risks in their application. In France however, the field of blood transfusions extends this obligation to the theoretical risk of potential transmission through the blood of the infectious agent responsible for Creutzfeldt-Jakob's disease. UNANSWERED QUESTIONS: From an ethical point of view, is information on the theoretical risk of transmission founded? From a formal point of view, the means used for such an extension (i.e.,a bulletin) is debatable; was this an adequate measure? THE RETURN OF COMMON SENSE: If we look at the earlier texts, the principle of an obligation to inform the patient of the theoretical risks does not appear widespread or even confirmed. Do these text simply the return of "common sense"? And if so, to what extent does it encourage the illusion of a zero risk...

Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial

International audienceIntroduction: The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.90, p < 0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61–0.88, p < 0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF.Methods: A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate.Results: The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16 years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold.Conclusions: The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshol

Public health and budget impacts of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Paraguay

This study aimed to investigate the public health and economic benefit of using a quadrivalent influenza vaccine (QIV) instead of a trivalent influenza vaccine (TIV) in past seasons in Paraguay. The budget impact of switching from TIV to QIV in the Immunization Program was also evaluated. The adapted model includes two modules. The first compared retrospectively Health and Economic outcomes resulting from the use of QIV instead of TIV. The second forecast the spending and savings that would be associated with the switch from TIV to QIV. Our findings estimate that the switch from TIV to QIV during the seasons 2012 to 2017 could have prevented around 2,600 influenza cases, 67 hospitalizations and 10 deaths. An alternative scenario using standardized estimates of the burden of influenza showed that 234 influenza-related hospitalizations and 29 deaths could have been prevented. The estimated annual budget impact of a full switch from TIV to QIV was around USD1,6 million both from the payer and societal perspectives. Those results are mainly driven by vaccine prices and coverage rate. In sum, this manuscript describes how the use of QIV instead of TIV could have prevented influenza cases and subsequent complications that led to hospitalizations and deaths. This could have generated savings for the health system and society, offsetting part of the additional investment needed to switch from TIV to QIV

Switching from trivalent to quadrivalent inactivated influenza vaccines in Uruguay: a cost-effectiveness analysis

We evaluated the cost-utility of replacing trivalent influenza vaccine (TIV) with quadrivalent influenza vaccine (QIV) in the current target populations in Uruguay. An existing decision-analytic static cost-effectiveness model was adapted for Uruguay. The population was stratified into age groups. Costs and outcomes were estimated for an average influenza season, based on observed rates from 2013 to 2019 inclusive. Introducing QIV instead of TIV in Uruguay would avoid around 740 additional influenza cases, 500 GP consultations, 15 hospitalizations, and three deaths, and save around 300 workdays, for the same vaccination coverage during an average influenza season. Most of the influenza-related consultations and hospitalizations would be avoided among children ≤4 and adults ≥65 years of age. Using QIV rather than TIV would cost an additional ~US$729,000, but this would be partially offset by savings in consultations and hospitalization costs. The incremental cost per quality-adjusted life-year (QALY) gained with QIV would be in the order of US$18,000 for both the payor and societal perspectives, for all age groups, and around US$12,000 for adults ≥65 years of age. The main drivers influencing the incremental cost-effectiveness ratio were the vaccine efficacy against the B strains and the percentage of match each season with the B strain included in TIV. Probabilistic sensitivity analysis showed that switching to QIV would provide a favorable cost-utility ratio for 50$20,000. A switch to QIV is expected to be cost-effective for the current target populations in Uruguay, particularly for older adults

Public health and economic impact of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Mexico

Most influenza vaccines in Mexico are trivalent, containing two influenza A strains and a single B strain. Quadrivalent influenza vaccines (QIVs) extend protection by including an additional B strain to cover both co-circulating B lineages. Here, we retrospectively estimated how a switch to QIV in Mexico would have impacted influenza-related health outcomes over the 2010/2011 to 2015/2016 influenza seasons, and prospectively estimated the budget impact of using QIV in Mexico’s national immunization program from 2016/2017 to 2020/2021. For the retrospective estimation, we used an age-stratified static model incorporating Mexico-specific input parameters. For the prospective estimation, we used a budget impact model based on retrospective attack rates considering predicted future vaccination coverage. Between 2010/2011 and 2015/2016, a switch to QIV would have prevented 270,596 additional influenza cases, 102,000 general practitioner consultations, 140,062 days of absenteeism, 3,323 hospitalizations, and 312 deaths, saving Mex$214 million (US$10.8 million) in third-party payer costs. In the prospective analysis, a switch to QIV was estimated to prevent an additional 225,497 influenza cases, 85,000 general practitioner consultations, 116,718 days of absenteeism, 2,769 hospitalizations, and 260 deaths, saving Mex$178 million (US$9 million) in third-party payer costs over 5 years. Compared to the trivalent vaccine, the benefit and costs saved with QIV were sensitive to the distribution of influenza A vs. B cases and trivalent vaccine effectiveness against the mismatched B strain. These results suggest switching to QIV in Mexico would benefit healthcare providers and society by preventing influenza cases, morbidity, and deaths, and reducing associated use of medical resources

Direct-acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-induced Cryoglobulinemia Vasculitis

International audienceBackground & AimsInterferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity.MethodsWe performed a prospective study of 27 consecutive patients with HCV-CV (median age 59 years) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France. Blood samples were collected from these patients before and after DAA therapy, and also from 12 healthy donors and 12 individuals with HCV infection without CV. HCV load, cryoglobulins, and cytokines were quantified by flow cytometry, cytokine multiplex assays, and ELISAs.ResultsTwenty-four patients (88.9%) had a complete clinical response of CV to DAA therapy at week 24, defined by improvement of all the affected organs and the absence of relapse. Compared to healthy donors and patients with HCV infection without CV, patients with HCV-CV, before DAA therapy, had a lower percentage of CD4+CD25hiFoxP3+ regulatory T cells (P<.01) but higher proportions of IgM+CD21–/low memory B cells (P<.05), CD4+IFNγ+ cells (P<.01), CD4+IL17A+ cells (P<.01), and CD4+CXCR5+IL21+ follicular T-helper (Tfh) cells (P<.01). In patients with HCV-CV, there was a negative correlation between numbers of IgM+CD21–/low memory B cells and T-regulatory cells (P=.03), and positive correlations with numbers of Tfh cells (P=.03) and serum levels of cryoglobulin (P=.01). DAA therapy increased patients’ numbers of T-regulatory cells (1.5%±0.18% before therapy vs 2.1%±0.18% after therapy), decreased percentages of IgM+CD21–/low memory B cells (35.7%±6.1% before therapy vs 14.9% ± 3.8% after therapy), and decreased numbers of Tfh cells (12%±1.3% before therapy vs 8%±0.9% after therapy). Expression levels of B lymphocyte stimulator receptor 3 and programmed cell death 1 on B cells increased in patients with HCV-CV after DAA-based therapy (mean fluorescence units, 37 ± 2.4 before therapy vs 47 ± 2.6 after therapy; P<.01 and 29 ± 7.3 before therapy vs 48 ± 9.3 after therapy; P<.05, respectively).ConclusionsIn a prospective clinical trial of patients with HCV-CV, DAA-based therapy restored disturbances in peripheral B- and T-cell homeostasis