A systematic review on the appropriate discounting rates for the economic evaluation of gene therapies: whether a specific approach is justified to tackle the challenges?

OBJECTIVES: Discounting the cost and effect for health intervention is a controversial topic over the last two decades. In particular, the cost-effectiveness of gene therapies is especially sensitive to the discount rate because of the substantial delay between the upfront cost incurred and long-lasing clinical benefits received. This study aims to investigate the influence of employing alternative discount rates on the incremental cost-effectiveness ratio (ICER) of gene therapies. METHODS: A systematic review was conducted to include health economic evaluations of gene therapies that were published until April 2023. RESULTS: Sensitivity or scenario analysis indicated that discount rate represented one of the most influential factors for the ICERs of gene therapies. Discount rate for cost and benefit was positively correlated with the cost-effectiveness of gene therapies, that is, a lower discount rate significantly improves the ICERs. The alternative discount rate employed in some cases could be powerful to alter the conclusion on whether gene therapies are cost-effective and acceptable for reimbursement. CONCLUSIONS: Although discount rate will have substantial influence on the ICERs of gene therapies, there lacks solid evidence to justify a different discounting rule for gene therapies. However, it is proposed that the discount rate in the reference case should be updated to reflect the real-time preference, which in turn will affect the ICERs and reimbursement of gene therapies more profoundly than conventional therapies.

Exploration of barriers and facilitators to the implementation of the DREPADO randomized controlled trial: A qualitative study.

PURPOSE: DREPADO is a randomized controlled trial (RCT) assessing the impact of a pediatric-adult transition program, on the health status of adolescents with sickle cell disease. Using a biopsychosocial approach with three main facets (educational, psychological and social interactions), it constitutes a complex transition program, which is quite difficult to implement. To facilitate the implementation of this complex program, the aim of this ancillary study is to explore barriers and facilitators at the early stages of this implementation. METHODS: A qualitative study with semi-structured interviews was conducted, according to COREQ quality criteria, in patients with sickle cell disease who had already experienced the transition to adult care before DREPADO, and healthcare professionals working on the DREPADO RCT. RESULTS: Semi-structured interviews were conducted with patients (n = 12) and healthcare professionals (n = 12) from November 2019 to May 2020. The main barriers identified by patients were time and implication required by this transition program. Healthcare professionals involved in the coordinating center mentioned changes in their working habits and also elements about the RCT regulatory procedures. Main facilitators reported by both patients and healthcare professionals were the positive perception of the transition program design, and especially the home setting for therapeutic education sessions. CONCLUSION: This study led to the identification of main barriers and facilitators to the implementation of both the DREPADO intervention and RCT. These propositions could also be used to promote other complex public health interventions or/and other randomized controlled trials.

Quality control of rigid endoscopes: a comparative study between ScopeControl® and surgeons' evaluation.

BACKGROUND: In central sterile services departments (CSSD), the functionality of rigid endoscopes, which are complex and fragile reusable devices, is usually controlled visually and is considered a complex and subjective task. ScopeControl® was developed to provide an automated quality control of rigid endoscopes by measuring the value of six parameters: viewing angle (VA), field of view (FV), color correctness (CC), light transmission (LT), fibers transmission (FT), and focus (FC). The aim of the present study was to assess the ability of ScopeControl® to pre-emptively identify endoscope defects before the surgeon considers them as defective. METHODS: The same endoscope was evaluated by surgeons during surgery using a scoring scale as well as the CSSD staff using the ScopeControl® during reprocessing. The ScopeControl® categorized the endoscope into 3 groups: "passed," "in danger," and "failed." Correlations between the surgeon's evaluation and results of the ScopeControl® were calculated. RESULTS: One hundred sixty-six controls were carried out concerning 51 different endoscopes. According to the surgeon's evaluation, 78.9% and 80.7% of controls were considered as satisfactory for image and brightness quality, respectively. Results obtained using ScopeControl® found that 13.3% of controls were considered as "passed," 31.3% "in danger," and 55.4% "failed," with poor correlation with the surgeons' evaluation. LT and FT parameters represented 95.2% of the reasons for failures. The ability of the ScopeControl® to detect endoscope defects earlier than surgeons was validated by tracking the results of endoscopes used and controlled several times. CONCLUSION: The ScopeControl® achieved an objective and consistent quality control of endoscopes and showed poor correlation with the surgeon's opinion. In practice, the ScopeControl® could avoid the use of defective endoscopes in the surgery unit and thus improve the quality of the surgical procedure.

Sickle cell disease perceptions of caregivers, adolescent, and adult patients: Barriers and facilitators to medical care adherence.

AIMS: To provide an understanding of medical care adherence factors as reported by caregivers, adolescent, and adult patients with sickle cell disease and to analyse those concerns to identify barriers and facilitators about medical care adherence. Three topics influenced medical care adherence: the disease itself, therapeutics, and the healthcare system. This study will focus on the first topic. DESIGN: Qualitative explorative study, using semi-structured and life-experience interviews and manual inductive content analysis. METHODS: From December 2016 - March 2017, one semi-structured interview was conducted by a researcher with each of the 15 adolescent patients, 10 adult patients, and 19 caregivers in a French public hospital. Interviews were audio-taped and transcribed before a content analysis. Perceptions were classified into barriers and facilitators of medical care adherence. RESULTS: This article presents disease perceptions of caregivers and patients (adolescents and adults): daily management and social representations. These perceptions differ among parents, adolescent patients, and adult patients. However, all report important disease-related "limitations" in their lives. The objective for adults (parents and patients) is to "live with the disease" and to achieve this, they find coping resources. Two major resources expressed by adults emerged: social resources (support from friends, patients' association, and social visibility) and disease knowledge (theoretical and derived from experience). This is not the case of adolescents for whom social normality was the main concern. CONCLUSION: Care management adherence is partly based on coping with the disease. Given the lower number of facilitators expressed by adolescents, it is essential to propose interventions in this population. It will help them cope with the disease and, consequently, optimize care management adherence. IMPACT: Showing differences among caregivers, adult, and adolescent patient perceptions, this study impact future care practices. It revealed needs of intervention for adolescents.

Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model.

PURPOSE: A first cost-effectiveness analysis has raised a strong concern regarding the cost of tumor treatment fields (TTF) added to maintenance temozolomide for patients with glioblastoma. This evaluation was based on effectiveness outcomes from an interim analysis of the pivotal trial, moreover it used a "standard" Markov model. Our objective was to update the cost-effectiveness evaluation using the more flexible potential of the "partitioned survival" model design and using the latest effectiveness data. METHODS: We developed the model with three mutually exclusive health states: stable disease, progressive disease, and dead. Good fit parametric models were developed for overall survival and progression free survival and these generated clinically plausible extrapolations beyond the observed data. We adopted the perspective of the French national health insurance and used a 20-year time horizon. Results were expressed as cost/life-years (LY) gained (LYG). RESULTS: The base case model generated incremental benefit of 0.604 LY at a cost of €453,848 which, after 4% annual discounting of benefits and costs, yielded an incremental cost effectiveness ratio (ICER) of €510,273/LYG. Using sensitivity analyses and bootstrapping methods results were found to be relatively robust and were only sensitive to TTF device costs and the modelling of overall survival. To achieve an ICER below €100,000/LYG would require a reduction in TTF device cost of approximately 85%. CONCLUSIONS: Using a different type of model and updated survival outcomes, our results show TTF remains an intervention that is not cost-effective, which greatly restrains its diffusion to potentially eligible patients.

Health-related quality of life during pregnancy: A repeated measures study of changes from the first trimester to birth.

INTRODUCTION: The objective was to evaluate the quality of life of pregnant women with a full-term birth from the first trimester to the 9th month using the EQ5D-3L questionnaire, comparing physiological, simple pathological, or complex pathological pregnancies. MATERIAL AND METHODS: A prospective cohort of 500 pregnant women over the age of 18 was monitored between 2015 and 2017 at the Toulouse University Hospital (France). The data were collected monthly with an online report. Given that the decrease in quality of life was not linear during pregnancy, unadjusted and adjusted piecewise linear regression models were performed, considering 3 periods of time during pregnancy: 3-4, 4-8, and 8-9 months. The 5 dimensions of the EQ5D-Index and perceived health status were also analyzed. RESULTS: In total, 1847 questionnaires were collected. Between the 4th and 8th months, the quality of life was lower for pathological pregnancies (P < 0.001) than for physiological ones and decreased over time for each type of pregnancy (physiological: -0.08 points per month, P < 0.001; simple pathological: -0.12 points per month, P < 0.001; complex pathological: -0.11 points per month, P < 0.001). Interestingly, the perceived health status was lower at the 9th month than at the 3rd month of pregnancy, for physiological pregnancies (mean difference = -10.5 points, P < 0.001), pathological pregnancies (mean difference = -10.0 points, P < 0.002), and for complex pathological pregnancies (mean difference = -7.8 points, P = 0.058). CONCLUSIONS: In our population, the quality of life decreased between the 4th and 8th months, and decreased to a greater degree in a pathological pregnancy.

Non-profit Drug Research and Development at a Crossroads.

In wealthy nations, non-profit drug R&D has been proposed to reduce the prices of medicines. We sought to review the ethical and economic issues concerning non-profit drug R&D companies, and the possible impact that their pricing strategy may have on the innovation efforts from for-profit companies targeting the same segment of the pharmaceutical market. There are two possible approaches to pricing drugs developed by non-profit R&D programs: pricing that maximises profits and "affordable" pricing that reflects the cost of manufacturing and distribution, plus a margin that ensures sustainability of the drug supply. Overall, the non-profits face ethical challenges - due to the lack of resources, they are unable to independently commercialize their products on a large scale; however, the antitrust law does not permit them to impose prices on potential licensees. Also, reduced prices for the innovative products may result in drying the for-profit R&D in the area.

[Quality of medication storage on hospital wards]. / Qualité du stockage des médicaments dans les unités de soins.

In order to meet regulations and limit the risks for patients, the quality of medication storage on hospital wards requires practical actions. They concern mainly the management of the emergency medication cabinets, conditions regarding supply and cold storage under controlled temperatures. Failures in the system may result in nurses carrying out risky procedures.

[A prevalence study to monitor the consumption of antibiotics]. / Une enquête de prévalence pour suivre la consommation en antibiotiques.

Following the second Antibiotics Plan, in association with the hospital hygiene operational team, the hospital pharmacy department of the Desgenettes military teaching hospital led a study into the prevalence of the prescribing of antibiotics in December 2011. The study highlighted the trends in prescriptions and assessed the effectiveness of corrective or preventive actions implemented following the first prevalence study of 2006, in particular the multidisciplinary antibiotherapy coordination meetings.

Understanding the gap between guidelines and influenza vaccination coverage in people with diabetes: a scoping review.

Background: Diabetes affects millions of people worldwide, making them more vulnerable to infections, including seasonal influenza. It is therefore particularly important for those suffering from diabetes to be vaccinated against influenza each year. However, influenza vaccination coverage remains low in this population. This review primarily aims to identify the determinants of influenza vaccination in people with diabetes (T1D or T2D). Secondly, it aims to assess main recommendations for influenza vaccination, vaccine effectiveness, vaccination coverage, and how education and pharmacists can encourage uptake of the vaccine in the diabetic population. Methods: A scoping review was conducted in January 2022 to systematically review evidence on influenza vaccination in people with diabetes using data from PubMed, Science Direct, and EM Premium with terms such as "Diabetes mellitus," "Immunization Programs," "Vaccination," and "Influenza Vaccines." Quality assessment and data extraction were independently conducted by two authors. Disagreements between the authors were resolved through discussion and consensus, and if necessary, by consulting a third author. Results: Of the 333 records identified, 55 studies met the eligibility criteria for inclusion in this review. Influenza vaccination was recommended for people ≥6 months. Despite effectiveness evidence showing a reduction in mortality and hospitalizations in people with diabetes vaccinated vs. non-vaccinated ones, very few studies reported a coverage rate ≥ 75%, which is WHO's target objective. Determinants such as advanced age, presence of comorbidities and healthcare givers' advice were associated with increased vaccination uptake. On the contrary, fear of adverse reactions and concerns about vaccine effectiveness were significant barriers. Finally, education and pharmacists' intervention played a key role in promoting vaccination and increasing vaccination uptake. Conclusion: Influenza vaccination coverage in people with diabetes remains low despite recommendations and evidence on vaccine effectiveness. Motivators and barriers as well as several socio-demographic and clinical factors have been identified to explain this trend. Efforts are now needed to increase the number of diabetics vaccinated against influenza, mainly through education and the involvement of healthcare givers.

Glossary of healthcare pathways: a methodological approach involving a transdisciplinary team in public health.

Introduction: The healthcare pathway is at the heart of public health organization concerns, but communication between the various players can be an obstacle. This work, produced by a French transdisciplinary team, offers a methodological approach based on formalized consensus to elaborate a glossary of healthcare pathways. A two-steps procedure was elaborated, including a double rounded Delphi method to formalize expert consensus, and two groups of experts: a workgroup and a review group. Methods: The workgroup provided a list of words or expressions that, in their opinion, described, evaluated or compared the healthcare pathways for patients, caregivers or regulators. The review group checked this list and added or deleted words or expressions. Then, definitions were added by the workgroup based into account three dimensions: official, academic and from the field. The review group validated the definitions and provided complementary proposals if needed. Results: After pooling the list of words proposed by each of the six members of the working group, 417 words/expressions were ranked. After the two rounds of evaluation, 294 words/expressions were rated "appropriate" and were analyzed by the review group. This group, after two rounds of evaluation, agreed on 263 words/expressions that were transmitted to the working group who defined them. These definitions were rated by the review group. The first round of evaluation established 195 definitions as being appropriated whereas 68 definitions were amended by the review group. Conclusion: This glossary supports transdisciplinary communication, reduces the extent of variations in practice and optimizes decision-making. International debate on all aspects might be strengthened by an improved understanding of the concept of health pathway.

[Improving collaboration between the pharmacy and the nurses]. / Améliorer la collaboration entre la pharmacie et les infirmierès.

In hospitals, improving collaboration between the diferent players in the health care chain is an ongoing issue. Numerous tools are available to facilitate interprofessional communication. Satisfaction surveys can be of particular interest.

Human Papillomaviruses in Adolescents: Knowledge, Attitudes, and Practices of Pharmacists Regarding Virus and Vaccination in France.

Human papillomaviruses (HPVs) are responsible for one of the most common sexually transmitted diseases in the world, and their oncogenic role has been well demonstrated in genital, anal, and oropharyngeal areas. However, a certain distrust and a lack of knowledge about this vaccine are perceptible among French adolescents and their parents. Thus, health professionals and, more particularly, pharmacists appear to be key persons to promote HPV vaccination and restore confidence in the target population. The present study aims to assess the knowledge, attitudes, and practices regarding HPV vaccination among pharmacists, particularly in boys, following the 2019 recommendation to vaccinate them. The present study was designed as a cross-sectional, quantitative, and descriptive survey that was conducted from March to September 2021 among pharmacists in France. 215 complete questionnaires were collected. Gaps in knowledge were found, only 21.4% and 8.4% obtained a high level of knowledge related to, respectively, HPV and vaccination. Pharmacists were confident in the HPV vaccine (94.4%), found it safe and useful, and felt that the promotion of the vaccine was part of their role (94.0%). However, only a few have already advised it, which they justify due to a lack of opportunity and forgetfulness. Faced with this, training, computerized reminders, or supportive materials could be implemented to improve the advice and thus the vaccination coverage. Finally, 64.2% were in favor of a pharmacy-based vaccination program. In conclusion, pharmacists are interested in this vaccination and the role of promoter. However, they need the means to facilitate this mission: training, computer alerts, supportive materials such as flyers, and the implementation of vaccination in pharmacies.

Epidemiology and Clinical Burden of Meningococcal Disease in France: Scoping Review.

Invasive meningococcal disease (IMD) remains a significant health concern due to its unpredictable nature and its rapid progression. Even if occurrence of IMD is strictly monitored by a national surveillance network, no information on long-term sequelae is reported, making it difficult to assess the entire clinical burden of IMD in France. The aim of this scoping review was to analyze the epidemiology and the clinical burden of IMD in France by reporting the main epidemiological parameters, and by describing the clinical consequences and the care pathway of patients. The process of the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to the Scoping Reviews guidelines. In France, the incidence of IMD cases has been fluctuating over time, characterized by an overall downward trend linked to a decrease in Sg B cases and the introduction of mandatory vaccination against Sg C. Sg W cases increased in recent years (from 5% to 21% in 2019). The case fatality rate remained constant (6-12.9%). The most frequently reported sequelae were severe neurological disorder, epilepsy, and anxiety. However, data on sequelae and care pathways were scarce. Further research should concentrate on providing robust identification of sequelae and the subsequent impact on quality of life, as well as on the organization of optimal care and support for patients and their families.

Exploring the Determinants of Polypharmacy Prescribing and Dispensing Behaviors in Primary Care for the Elderly-Qualitative Study.

Polypharmacy is particularly prevalent in the elderly. The interest in this issue is growing, and many interventions exist to improve the appropriate use of polypharmacy for older people. However, evidence of their effectiveness is still limited. Thus, the aim of this study, based on a qualitative approach, was to identify the key elements perceived to influence the prescribing and dispensing of appropriate polypharmacy to older people in primary care. Semistructured interviews were conducted with general practitioners and community pharmacists practicing in the region of Nouvelle-Aquitaine (France). Pre-existing topic guides based on the 12 TDF domains have been adapted and used. Data were analyzed using the framework method and content analysis. A focus group of healthcare professionals was conducted, and behavior change techniques (BCTs) were used to select the intervention components. Seventeen interviews were convened. A wide range of determinants were identified as barriers and/or facilitators. Nine domains were selected as key domains to target for intervention. Five intervention components (behavior change techniques-BCTs) to include in an intervention were finally selected. The results of this study will serve as a starting point for the design of a theory-based intervention targeting healthcare professionals to improve appropriate prescribing and dispensing of polypharmacy for older people in primary care.

Implicit factors influencing the HTA deliberative processes in 5 European countries: results from a mixed-methods research.

Background: Health technology assessment (HTA) bodies across Europe rely on explicit factors for decision making. However, additional undefined factors play a role. This mixed-methods research aimed to identify the implicit factors involved in HTA deliberative processes in five European countries, and to analyze their impact on decision making. Methods: Between February and May 2021, semi-structured interviews (n = 20) were conducted with HTA experts of three different profiles (chair, advisor, and committee member) from France, Germany, Italy, Spain, and the United Kingdom. The degree of influence of a set of implicit factors and attributes that play a role in the HTA deliberative process, as previously identified in a systematic literature review, was scored by the experts. Experts were also asked to make recommendations on ways of improving the deliberative process. A qualitative analysis and descriptive statistics of quantitative variables are reported. Results: Most (18/20) experts concurred that implicit factors play a role in the HTA deliberative process. Recommendations for improving the process fell into three categories: transparency, methodology improvement, and stakeholder involvement. The results suggest a need for 1) increased external involvement HTA and 2) development of a methodology to mitigate the influence of implicit factors in the deliberative process. This could be achieved by updating the current frameworks to acknowledge these implicit factors and by developing methods to address them.

Relevance of early management by proton-pump inhibitor in acute upper gastro-intestinal tract disorder: A scoping review.

BACKGROUND: Proton-pump inhibitors (PPI) are frequently used in the emergency and general practice settings in several clinical presentations linked to acute upper gastro-intestinal tract disorders as abdominal or chest pain without recommendations. OBJECTIVE: The aim of this scoping review was to assess pain reduction, diagnostic performance, and safety in the first 24 h-management in primary care or emergency medicine. METHODS: Search was realized by 2 independent reviewers in PubMed, Embase, and Web of Science following PRISMA-ScR guidelines. Only original articles or systematic reviews in English were included. Studies about chronic and/or bleeding conditions, therapeutic cocktails and studies without pain evaluation were excluded. Two methodologies were used for bias estimation. RESULTS: From 4442 titles, 79 full-text articles were assessed, and 9 were included. There is no strong evidence supporting the use of PPI as a first line analgesic or diagnostic test in acute syndromes linked to acute upper gastro-intestinal tract disorder. A small effect in pain reduction was retrieved in patients with low pain scores. A poor additional value in patients with gastric reflux, and a low specificity compared to other diagnostic tests were observed. A short-term PPI administration appears to be safe with low risk of serious allergic reactions, and poor adverse effects (moderate evidence). CONCLUSION: Although PPIs may contribute to the multimodal analgesia in acute settings, with few and/or minor side effects, no recommendation can be drawn for their use as a primary analgesic. Data regarding the relevance of the PPI test are much less clear, no data regarding care pathways are available.

Association between health literacy and medication adherence in chronic diseases: a recent systematic review.

BACKGROUND: Poor medication adherence is a serious barrier to successful chronic disease management. Previous reviews reported that low health literacy could be associated with medication non-adherence but conclusions were uncertain. AIM: The aim of this systematic review was to clarify the relationship between health literacy and medication adherence in adults with chronic diseases. A secondary objective was to identify the factors that influence medication adherence. METHOD: Publications analyzing the relationship between health literacy and adherence in adults with chronic diseases were identified through 6 databases between 2015 and 2020. A quality assessment was conducted in order to improve the interpretation of the relationship between health literacy and medication adherence. A narrative synthesis was then performed to describe the relationship between health literacy and medication adherence. The factors influencing medication adherence were then analyzed as a secondary outcome. RESULTS: Among the 27 studies, 17 and 10 were considered to be of good and medium methodological quality, respectively. Concerning the relationship between health literacy and adherence, 14 reported a positive relationship, 1 study suggested a negative relationship, 3 found mixed results, and 9 reported not finding a relationship. Patient-related factors such as medication beliefs, self-efficacy, or medication knowledge, as well as demographic factors such as ethnic minority and incomes influence medication adherence. CONCLUSION: The present review confirms an unclear relationship between health literacy and medication adherence. Although health literacy plays a substantial role in medication adherence, other factors must be taken into account when addressing non-adherence.

Supporting health education policies: translation, cross-cultural adaptation and validation of a health literacy instrument, in French.

Background: Oral health is a fundamental human right and is inseparable and indivisible from overall health and well-being. Oral Health Literacy (OHL) has been proved to be fundamental to promoting oral health and reducing oral health inequalities. To our knowledge, no OHL instrument to evaluate OHL level is currently validated in French language despite the fact it is the fifth most widely spoken languages on the planet. The Oral health literacy Instrument (OHLI) appears to be the most interesting OHL instrument to adapt into French because it is already available in English, Spanish, Russian, Malaysian, and it contains both reading comprehension and numeracy sections. Its psychometric properties have been rated as adequate. Objective: The aim of this study was to translate and adapt cross-culturally the OHLI into French, to evaluate its psychometric properties and to compare its results to oral health knowledge. Method: This study followed and applied well-established processes of translation, cross-cultural adaptation and validation, based on the recommendations of the World Health Organization guidelines and on the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) study design checklist for patient-reported outcomes. Two psychometric assessments were planned, the comparison of OHLI-F scores according to education level and frequency of dental visits, and the test-retest reliability of the OHLI-F. Results: A total of 284 participants answered the OHLI-F. The OHLI-F scores were significantly different between participants with different levels of education and frequency of dental visits (p < 0.001). Participants with an education level lower than the baccalaureate, and those who never visit the dentist or only in case of pain, had significantly lower OHLI-F scores. Internal consistency was excellent (Cronbach's alpha = 0.881-0.914). Test-retest reliability was very high (intraclass correlation = 0.985 to 0.996). Conclusion: The OHLI-F has demonstrated adequate psychometric properties and can therefore be used to measure oral health literacy in French-speaking populations.