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Substance use is a global phenomenon that is particularly affecting the prison population. This study aimed to describe the prevalence of drug use among people in prison before and during incarceration in seven European countries and to compare it with the prevalence in the general population. Individual data collection was carried out between 2014 and 2018 with a model European Questionnaire on Drug Use among people in prison. A total of 12,918 people living in prison filled in the survey. People in prison report higher level of drug use when compared with the general population and the use of drug inside prison exist, although at lower levels when compared with predetention. Prisons can represent a point of access to engage individuals who use drugs in interventions that address drug use and risk factors related to both drug use and imprisonment. [ABSTRACT FROM AUTHOR]

Introduction: Access to medicines is a shared goal across healthcare stakeholders. Since health technology assessment (HTA) informs funding decisions, it shapes access to medicines. Despite its wide implementation, significant access variations due to HTA are observed across Europe. This paper elicited the opinions of European stakeholders on how HTA can be improved to facilitate access. Methods: A scoping review identified HTA features that influence access to medicines within markets and areas for improvement, while three access dimensions were identified (availability, affordability, timeliness). Using the Delphi method, we elicited the opinions of European stakeholders to validate the literature findings. Results: Nineteen participants from 14 countries participated in the Delphi panel. Thirteen HTA features that could be improved to optimise access to medicines in Europe were identified. Of these, 11 recorded a positive impact on at least one of the three access dimensions. HTA features had mostly a positive impact on timeliness and a less clear impact on affordability. 'Early scientific advice' and 'clarity in evidentiary requirements' showed a positive impact on all access dimensions. 'Established ways to deal with uncertainty during HTA' could improve medicines' availability and timeliness, while more 'reliance on real-world evidence' could expedite time to market access. Conclusions: Our results reiterate that increased transparency during HTA and the decision-making processes is essential; the use of and reliance on new evidence generation such as real-world evidence can optimise the availability of medicines; and better collaborations between regulatory institutions within and between countries are paramount for better access to medicines. [ABSTRACT FROM AUTHOR]

Many researchers, consumer groups, activists and civil society organizations agree that the pharmaceutical sector has been left too much to the private sector, which is solely driven by a profit motive. Therefore, it is imperative to take a bold initiative to turn the idea of medicine, pharmaceutical products, and health technology as a common good into a reality. We propose to establish a European institute that can oversee an ambitious research portfolio. This institute can provide research grants or do in-house research but, in any case, any intellectual property rights emanating from the research will have to be shared in the interest of the public good. A collective knowledge pool, where all results and technological knowledge are gathered and shared, will likewise be part of the institute. Any final product developed within the Institute will be subject to an open license. We ensure that all necessary data and information remain public and that know-how about the production of a medicine can be passed on to those who need it. Finally, this institute should have a focus on production and distribution. Price, quality, availability and even working conditions of the staff will be criteria in any bidding process. [ABSTRACT FROM AUTHOR]

Background: Youth mortality from drugs is worryingly increasing in Europe. Little is so far known about what substance use services are available to young people. An out-of-home care placement is often used but does not suffice alone as an intervention in problematic substance use among youth. Additional interventions are needed. Objective: This narrative review investigated what has been done, what works, and what is needed in treating youth substance use in the Nordic countries from the viewpoint of social services. This study brought together previous Nordic studies on this topic and presented responses to youth substance use in Nordic social welfare system to the wider international audience. Methods: A search of the ProQuest and EBSCOhost databases revealed seven interventions reported in 17 papers. Narrative synthesis was used. Results: Interventions included the Cannabis Cessation Program (CCP), the Icelandic version of the Motivation to Change Inventory for Adolescents, the Norwegian multisystemic therapy program (MST), the Structured Interview Manual UngDOK implemented in the Swedish Maria clinics, the Finnish ADSUME-based intervention in school health care, and the Swedish Comet 12–18 and ParentStep 13–17 programs. Many interventions had originated in the US rather than in the Nordic countries and most of them were adapted from adult interventions when youth specificity was lacking. Parental involvement was deemed important, but ineffective without involving the adolescent themself. Interventions and ways for dealing with young offenders required reconsideration from the perspective of the best interests of the child. The current research focuses on universal prevention while more knowledge about selective and indicative prevention was called for. Conclusions: Not enough is known about the cessation of problematic youth substance use and subsequent rehabilitation in social services. We would encourage further research on the multi-producer system, subscriber-provider-cooperation in youth substance use services, non-medical youth-specific substance use interventions in social services, and rehabilitative juvenile drug offense practices. [ABSTRACT FROM AUTHOR]

Background: Studies revealed unidirectional associations between frailty and medication‐related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi‐directional association between frailty and the risk of MRPs in community‐dwelling older adults in five European countries. Methods: Participants were 1785 older adults in the population‐based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one‐year follow‐up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross‐lagged panel modeling was used to assess bi‐directional associations. Results: The unidirectional association between frailty at baseline and the risk of MRPs at follow‐up remained statistically significant after adjusting for covariates (β = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow‐up shows similar trends. The bi‐directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow‐up than reversed path (Wald test for comparing lagged effects: p < 0.05). Conclusion: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways. [ABSTRACT FROM AUTHOR]

Background: Although expanded access is an increasingly used pathway for patients to access investigational medicine, little is known on the magnitude and content of published scientific research collected via expanded access. Methods: We performed a review of all peer-reviewed expanded access publications between January 1, 2000 and January 1, 2022. We analyzed the publications for drugs, diseases, disease area, patient numbers, time, geographical location, subject, and research methodology (single center/multicenter, international/national, prospective/retrospective). We additionally analyzed endpoints reported in all COVID-19-related expanded access publications. Results: We screened 3810 articles and included 1231, describing 523 drugs for 354 diseases for 507,481 patients. The number of publications significantly increased over time ( p < 0.001 ). Large geographical disparities existed as Europe and the Americas accounted for 87.4% of all publications, whereas Africa only accounted for 0.6%. Oncology and hematology accounted for 53% of all publications. Twenty-nine percent of all expanded access patients (N = 197,187) reported on in 2020 and 2021 were treated in the context of COVID-19. Conclusions: By summarizing characteristics of patients, diseases, and research methods described in all scientific literature published on expanded access, we provide a unique dataset for future research. We show that published scientific research on expanded access has surged over the past decades, partly due to COVID-19. However, international collaboration and equity in geographic access remain an issue of concern. Lastly, we stress the need for harmonization of research legislation and guidance on the value of expanded access data within real-world data frameworks to improve equity in patient access and streamline future expanded access research. [ABSTRACT FROM AUTHOR]

Background: The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA's positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions. Methods: Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals. Results: Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was > 90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged. Conclusion: In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally. [ABSTRACT FROM AUTHOR]

Since the industrial revolution, the relationship between unemployment and psychiatric disorders has been a subject of high interest. Currently, regarding the correlation between unemployment and substance-use disorders (SUDs), only older, often isolated and fragmented research results are available in the literature. This review was based on an extensive literature search of the European and North American literature in most relevant databases for "unemployment" and "substance use" related to "drugs", "alcohol", "nicotine", and "tobacco" between November 2022 and January 2023, according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) guidelines. A total of 59,117 papers were identified, of which only 33 articles were identified as relevant to the research objective. The literature showed significantly higher prevalence rates of SUDs involving divergent psychotropic substances among unemployed people. Unemployment was found to be a risk factor for SUD, and vice versa. However, the correlation between unemployment and relapses or smoking cessation was inconsistent. In addition, there appeared to be a mild effect of business cycles on SUD. The results showed significant multifaceted correlations between unemployment and SUD, indicating that prevention and early intervention are required to prevent harmful psychosocial consequences, such as social disintegration and severe psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology (SIOPE) Essential Anticancer Medicines Project was to provide a list of anticancer medicines that are considered essential in the treatment of paediatric cancers to help ensure their continuous access to all children and adolescents with cancer across Europe.Methods: This pan-European project, done between Jan 20, 2020, and Feb 18, 2022, was designed to be a systematic collection and review of treatment protocols and strategies that are used to treat childhood cancer in Europe. We formed 16 working groups on the basis of paediatric cancer types, and which were based on the existing SIOPE Clinical Trial Groups. Workings groups consisted of representatives from the SIOPE Clinical Trial Groups, Young SIOPE members, and senior paediatric oncology experts. Each group collected existing treatment protocols that are used to treat the respective cancer types in Europe. Medicines from the standard group of each protocol were extracted. For medicines not on the WHO Essential Medicines List for children (EMLc) 2017, working groups did a literature search to determine whether the medicines should be defined as essential, promising, or neither essential nor promising. Each group provided an individual summary, and all medicines that were considered essential by at least one group were combined in a joint list.Findings: The working groups identified 73 treatment protocols used in Europe and defined 66 medicines as essential. For several newer medicines, such as kinase inhibitors or tisagenlecleucel, the supporting evidence was insufficient to consider them essential, so these medicines were defined as promising. 25 medicines were considered promising by at least one working group. 22 (33%) of the 66 essential and none of the promising medicines were included in the WHO EMLc 2017. The WHO EMLc 2021 included two new medicines (everolimus and vinorelbine) following applications we made as a result of this project.Interpretation: Medicines that were defined as essential within this project should be available for the treatment of childhood and adolescent cancer continuously and across Europe. This list can be used to support and guide stakeholders and policy makers in negotiations on a national and European level regarding shortages, accessibility, and affordability of these medicines.Funding: None. [ABSTRACT FROM AUTHOR]

Older adults with dementia commonly receive multiple medications and have higher hospitalization rates, elevating the risk of potentially inappropriate prescribing and in-hospital adverse drug reactions (ADRs). There is limited evidence examining ADRs in older adults with dementia during hospitalization. Our aim was to assess the association between dementia and incidence of ADRs during hospitalization and to identify prevalent types of ADRs and medications linked to ADRs. Secondary analysis of the SENATOR trial database, which was a randomized controlled trial of an intervention to reduce ADRs in older inpatients with multimorbidity. A total of 1537 patients (47.2% females) with a mean age of 78.1 years were recruited from 6 European hospitals. Sociodemographic data, functional status, cognitive status, clinical information, and ADR-related outcomes were extracted from the SENATOR database. Inpatients with dementia were identified based on prior International Classification of Diseases, Tenth Revision (ICD-10), dementia diagnosis, receiving acetylcholinesterase inhibitors or memantine, or a Mini-Mental State Examination score ≤24 at admission without concurrent delirium. Among participants, 392 (25.5%) were identified as having dementia. The proportion of patients with probable or certain incident in-hospital ADRs was similar between the groups with and without dementia (22.4% vs 25.4%, P >.05). However, in-hospital rates of probable or certain ADRs from 12 common categories were less frequently identified in patients with dementia compared to those without (19.4% vs 23%, P =.025). Major constipation (6.4% vs 9.9%, P =.03) and acute dyspepsia, nausea, or vomiting (2.8% vs 5%, P =.03) were less commonly observed ADRs in patients with dementia. We did not observe an increased risk of in-hospital ADRs among inpatients with dementia. However, ADRs related to the gastrointestinal tract and identified by subjective symptoms were less frequently identified in this group. This study lays the groundwork for developing new tools for ADR diagnosis for older patients with dementia. [ABSTRACT FROM AUTHOR]

Background: Studies on medication safety in pregnancy are increasingly focusing on child neurodevelopmental outcomes. Establishing neurodevelopmental safety is complex due to the range of neurodevelopmental outcomes and the length of follow-up needed for accurate assessment. The aim of this study was to provide an inventory of European data sources for use in pharmacoepidemiologic studies investigating neurodevelopment following maternal medication exposure. Method: The EUROmediSAFE inventory of data sources in Europe for evaluating perinatal and long-term childhood risks associated with in-utero exposure to medication was updated by contacting colleagues across 31 European countries, literature review and internet searches. Included data sources must record at least one neurodevelopmental outcome and maternal medication use in pregnancy must be available, either in the data source itself or through linkage with another data source. Information on the domain of neurodevelopment, measure/scale used and the approach to measurement were recorded for each data source. Results: Ninety data sources were identified across 14 countries. The majority (63.3%) were created for health surveillance and research with the remaining serving administrative purposes (21.1% healthcare databases,15.6% other administrative databases). Five domains of neurodevelopment were identified—infant development (36 data sources,13 countries), child behaviour (27 data sources, 10 countries), cognition (29 data sources, 12 countries), educational achievement (20 data sources, 7 countries), and diagnostic codes for neurodevelopmental disorders (42 data sources, 11 countries). Thirty-nine data sources, in 12 countries, had information on more than one domain of neurodevelopment. Conclusion: This inventory is invaluable to future studies planning to investigate the neurodevelopmental impact of medication exposures during pregnancy. Caution must be used when combining varied approaches to neurodevelopment outcome measurement, the age of children in the data source, and the sensitivity and specificity of the outcome measure selected should be borne in mind. [ABSTRACT FROM AUTHOR]

Introduction: Involving patients in decision making adds value in the context of pharmacovigilance (PV). This added value goes beyond participation in spontaneous reporting systems for adverse drug reactions. However, there is a gap between allowing patients to report and actual patient involvement. Views regarding best practices from regulators, patient organizations and pharmaceutical companies could help increase and improve patient involvement in PV.Objective: The aim of this study was to investigate the factors contributing to best practices for patient involvement in PV and to develop a definition of patient involvement based on a qualitative multistakeholder study across Europe.Methods: A literature review was conducted to map the field of study and obtain insights for the elaboration of an interview guide. Subsequently, patient representatives, members of the pharmaceutical industry and regulators were invited to participate in interviews. These interviews were analyzed using NVIVO® software and employing reflective thematic analysis.Results: A total of 20 interviews were conducted with representatives at both the national and European levels. The best practices identified were engagement from the start, face-to-face communication, a full circle of feedback, same-level partners, structured involvement and guidelines, establishing common goals, patient education and empowerment, and developing trust and balance. These activities can be implemented via deep collaboration among stakeholders. A definition of patient involvement was constructed in accordance with the input of all stakeholder groups, which reflects the involvement of all types of patients at all levels of the decision-making process.Conclusion: In this study, we developed a definition for patient involvement based on qualitative interviews. The factors contributing to best practices for patient involvement were mentioned across stakeholder groups and aimed to stimulate patient involvement in PV. Patients are eager to become equal partners and to engage effortlessly in the same manner as other stakeholders. [ABSTRACT FROM AUTHOR]

Background: Co‐medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis‐related search patterns in Google Trends. This study aims to assess AR co‐medication and its regional patterns in Europe, using real‐world data. Methods: We analysed 2015–2020 MASK‐air® European data. We compared days under no medication, monotherapy and co‐medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co‐medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co‐medication (p <.001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1‐antihistamines were the most common medication in single and co‐medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. Conclusions: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co‐medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co‐medication use is driven by symptom severity. [ABSTRACT FROM AUTHOR]

Background: Medication non-adherence jeopardises the effectiveness of chronic therapies and negatively affects financial sustainability of healthcare systems. Available medication adherence-enhancing interventions (MAEIs) are utilised infrequently, and even more rarely reimbursed. The aim of this paper was to review reimbursed MAEIs across selected European countries. Methods: Data on reimbursed MAEIs were collected from European countries at the ENABLE Cost Action expert meeting in September 2021. The identified MAEIs were analysed and clustered according to their characteristics, direct vs. indirect relation to adherence, and the targeted adherence phase. Results: Out of 12 contributing countries, 10 reported reimbursed MAEIs, 28 in total, of which 20 were identified as MAEIs targeting adherence directly. Reimbursed MAEIs were most often performed by either doctors (n = 6), nurses (n = 6), or pharmacists (n = 3). The most common types of MAEIs were education (n = 6), medication regimen management (n = 5), and adherence monitoring feedback (n = 4). Only seven reimbursed MAEIs were technology-mediated, whereas 11 addressed two interlinked phases of medication adherence, i.e., implementation and persistence. Conclusion: Our review highlights the scarcity of reimbursed MAEIs across the selected European countries, and calls for their more frequent use and reimbursement. [ABSTRACT FROM AUTHOR]

The medical profession is calling for an EU strategy against drug supply shortages. At the 69th Consultative Meeting of German-speaking medical organizations, a communiqué was adopted, highlighting the increasing gaps in medication supply in Europe. The relocation of pharmaceutical production facilities to Asia further exacerbates the situation. Diversification of supply chains, strengthening the production of medicines and active ingredients in Europe, as well as effective measures for sufficient stockpiling, are demanded. The policy is urged to develop a strategy against dependence on Asian production facilities. [Extracted from the article]

The article focuses on the European regulators' decision to withhold approval for a new Alzheimer's drug Leqembi and discusses the division of opinions regarding the treatment, the drug's mechanism and associated risks, and the contrast with approvals in other countries.

Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process. [ABSTRACT FROM AUTHOR]

P. aeruginosa is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many countries, especially in the eastern and south-eastern parts of Europe. The aim of this narrative review is to provide a comprehensive assessment of the epidemiology, latest data, and clinical evidence on the current and new available drugs active against P. aeruginosa isolates with limited treatment options. The latest evidence and recommendations supporting the use of ceftolozane-tazobactam and ceftazidime-avibactam, characterized by targeted clinical activity against a significant proportion of P. aeruginosa strains with limited treatment options, are described based on a review of the latest microbiological and clinical studies. Cefiderocol, with excellent in vitro activity against P. aeruginosa isolates, good stability to all β-lactamases and against porin and efflux pumps mutations, is also examined. New carbapenem combinations are explored, reviewing the latest experimental and initial clinical evidence. One section is devoted to a review of new anti-pseudomonal antibiotics in the pipeline, such as cefepime-taniborbactam and cefepime-zidebactam. Finally, other "old" antimicrobials, mainly fosfomycin, that can be used as combination strategies, are described. [ABSTRACT FROM AUTHOR]

Background: Five-day oral therapies against early COVID-19 infection have recently been conditionally approved in Europe. In the drug combination nirmatrelvir + ritonavir (nirmatrelvir/r), the active agent, nirmatrelvir, is made bioavailable in clinically adequate amounts by the additional administration of a potent inhibitor of its first-pass metabolism by way of cytochrome P450 [CYP] 3A in the gut and liver. In view of the central role of CYP3A in the clearance of many different kinds of drugs, and the fact that many patients with COVID-19 are taking multiple drugs to treat other conditions, it is important to assess the potential for drug interactions when nirmatrelvir/r is given, and to minimize the risks associated with such interactions. Methods: We defined the interaction profile of ritonavir on the basis of information derived from two databases (Medline, GoogleScholar), three standard electronic texts on drug interactions, and manufacturer-supplied drug information. We compiled a list of drugs and their potentially relevant interactions, developed a risk minimization algorithm, and applied it to the substances in question. We also compiled a list of commonly prescribed drugs for which there is no risk of interaction with nirmatrelvir/r. Results: Out of 190 drugs and drug combinations, 57 do not need any special measures when given in combination with brief, low-dose ritonavir treatment, while 15 require dose modification or a therapeutic alternative, 8 can be temporarily discontinued, 9 contraindicate ritonavir use, and 102 should preferably be combined with a different treatment. Conclusion: We have proposed measures that are simple to carry out for the main types of drug that can interact with ritonavir. These measures can be implemented under quarantine conditions before starting a 5-day treatment with nirmatrelvir/r. [ABSTRACT FROM AUTHOR]

There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate. We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision. Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193–751), 141 days (range 77–517) and 515 days (range 0–780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days. This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology. • Health technology assessments of paediatric oncology drugs vary greatly within Europe. • The timing of HTA evaluation adds to the delay of patient access. • Differences between adult and paediatric trial methodology should be considered. • Multistakeholder collaboration between EMA, academia, pharmaceutical companies, patients advocates and HTAs is needed. [ABSTRACT FROM AUTHOR]

Objective: This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health‐related quality of life, health status, work productivity, and healthcare resource utilization. Methods: This cross‐sectional study utilized SF‐12, EQ‐5D‐5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self‐reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx‐treated or Rx‐untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. Results: Of 2086 respondents with CLBP, 683 had mild pain (276 Rx‐untreated, 407 Rx‐treated) and 1403 had moderate/severe pain (781 Rx‐untreated, 622 Rx‐treated). Respondents with moderate/severe pain had significantly worse health‐related quality of life (SF‐12v2 physical component summary), health status (EQ‐5D‐5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx‐untreated (moderate/severe pain Rx‐untreated vs. mild pain Rx‐untreated, p ≤ 0.05) and Rx‐treated (moderate/severe pain Rx‐treated vs. mild pain Rx‐treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx‐treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx‐untreated (8.72 vs. 7.61, p = 0.072) groups. Health‐related quality of life (SF‐12v2 physical component summary) and health status (EQ‐5D‐5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx‐treated group compared with all other groups (all p ≤ 0.05). Conclusion: Greater severity of CLBP was associated with worse health‐related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to outline the challenges of implementing outcomes-based contracts (OBCs) in Europe. Methods: A scoping review was conducted, building on the searches of a previous systematic review and updating them for December 2017 until May 2021. The combined results were screened, based on inclusion and exclusion criteria. All identified studies published in the English language that described specific OBC schemes for medicines in European countries were included. Insights into the challenges of OBCs were extracted and analysed to develop a conceptual framework. Results: Ten articles from the previous systematic review matched our inclusion criteria, along with 14 articles from electronic searches. Analysis of these 24 articles and classification of the challenges revealed that there are multiple barriers that must be overcome if OBCs that benefit all stakeholders are going to be adopted widely across Europe. These challenges were grouped according to five key themes: negotiation framework; outcomes; data; administration and implementation; and laws and regulation. Conclusions: If the promise of OBCs is to be fully realised in Europe, there remain major challenges that need to be overcome by all stakeholders working in partnership. The overlapping and interconnected nature of these challenges highlights the complexity of OBC arrangements. [ABSTRACT FROM AUTHOR]

Background: Language discrepancies may create barriers to healthcare, compromise the quality of care and worsen health outcomes. This study explored what European countries currently do to ensure that foreign patients receive sufficient information about their medications if they do not understand the country's national language. Methods: A questionnaire was distributed to the delegates of two Council of Europe committees. The recipients were asked to provide insights on how their country facilitates access to the necessary product information when patients do not understand the national language. Results: Seventeen out of 39 delegates completed the questionnaire. The majority of the respondents indicated that all healthcare professionals experience difficulties in providing guidance and advice to foreign patients. The results also showed that different methods are used nationally to present the necessary information to foreigners. Finally, the observations from this survey suggested that electronic leaflets in the patient's primary language could be a valuable option to improve access to medication-related information. Conclusions: Healthcare professionals seem to encounter challenges in providing foreign patients with information associated with medication use. Electronic leaflets can be one of the tools for improving communication between these patients and healthcare professionals to ensure that medicines are used safely and effectively. [ABSTRACT FROM AUTHOR]

On the 24th of February 2022, the Russian Federation began an unprovoked invasion of Ukraine, marking the biggest military attack in Europe since the second world war. Over 4 million people have fled their homeland within the first month of the war and have triggered a large refugee crisis with impacts far beyond the Ukrainian border. People in the neighboring countries have shown tremendous support by stepping forward to donate food, clothes, medications, money, and other essential supplies. The governments and other regional stakeholders have also been supportive in accommodating and easing regulations for the incoming refugees. Herein, we summarize the humanitarian measures and medical donations that have been made by European countries as they stepped up their efforts to provide refugees with all necessary basic services. We further highlight potential oncoming challenges in Ukraine and the host countries along with relevant solutions to these challenges. The current scenario highlights the need for multi-party and multi-level collaborations (both public and private) to tackle the emerging situation. [ABSTRACT FROM AUTHOR]

Background: In recent years, innovation in oncology has created new challenges for pricing and reimbursement systems. Oncology medicines with multiple indications face a number of access challenges: (1) the number of assessments and administrative burden; (2) aligning price to different values of the same product; (3) managing clinical uncertainty at time of launch; and (4) managing budget uncertainty. These challenges impact a range of stakeholders and can result in delayed patient access to life-saving treatments. Consequently, countries have taken steps to facilitate patient access. Methods: Drawing on the experience across Europe we have reviewed different mechanisms countries have adopted that address these challenges. These include approaches aimed directly at the issue, multi-year-multi-indication (MYMI) agreements (BE, NL), and other approaches to manage access: flexible access agreements for new indications with clinical uncertainty (UK); development of a new agreement for each new indication (IT); and immediate access for new indications and bundled assessments (DE). Results: MYMI agreements are valuable where existing rules mean that every indication faces the same upfront evaluation process that delays patient access. They are also useful in managing budget impact and uncertainty. Other approaches that adopt an indication-specific approach helps manage clinical uncertainty at the time of launch and realise different values for the same product. They can help align price to value, even though indication-based pricing does not exist. Bundled assessments reduce the administrative burden for stakeholders, and the benefits of immediate reimbursement is that patient access is not delayed. Conclusion: The challenges for medicines with multiple indications impact a range of stakeholders and can result in delayed patient access to life-saving treatments. MYMI agreements have created a more pragmatic approach to HTA for medicines with multiple indications to ensure both fast and broad patient access. Continued innovation in oncology will require further innovative approaches in pricing and reimbursement. It is important that policymakers, payers and manufacturers engage in early discussions and are willing to find new solutions to help accelerate patient access to innovative therapies. [ABSTRACT FROM AUTHOR]

Background: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease., Methods: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019., Results: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV., Conclusions: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries., (© 2024. The Author(s).)

The presence of pharmacologically active compounds (PhACs) in surface waters poses an environmental risk of chronic exposure to nontarget organisms, which is a well-established and serious concern worldwide. Our aim was to determine the temporal changes in ecological risk quotient (RQ) based on the concentrations of 42 PhACs from six sampling sites on seven sampling dates in the water of a freshwater lake in Central Europe preferentially visited by tourists. Our hypothesis was that the environmental risk increases during the summer holiday season due to the influence of tourists. Different experimental toxicological threshold concentrations and seasonal measured environmental concentrations of 16 PhACs were applied to ecological risk assessment. RQs of 4 dominant PhACs (diclofenac, estrone [E1], estradiol [E2], and caffeine) indicated high ecological risk (RQ > 1) for freshwater ecosystems. Additionally, our results confirmed the assumptions that the high tourist season had a significant impact on the calculated RQ; however, these results are mainly due to the concentration and temporal change of particular PhACs, including diclofenac (5.3-419.4 ng/L), E1 (0.1-5.5 ng/L), and E2 (0.1-19.6 ng/L). The seasonal dependent highest RQs changed as follows: 9.80 (June 2017; E2), 1.23 (August 2017; E1), 0.43 (November 2017; E1), 0.51 (April 2018; E1), 5.58 (June 2018, diclofenac), 39.50 (August 2018; diclofenac), and 30.60 (October 2018; diclofenac). [ABSTRACT FROM AUTHOR]

In the article, the authors discuss how to address the interchangeability of biosimilars in the pharmaceutical industry. Also cited are how biosimilars reduced costs and boosted patient access to essential biological therapies, how biosimilars enhanced the accessibility and affordability of biological medicines for patients and the healthcare systems, and the dichotomy to the quick adoption of innovative medicines.

To ensure equitable access to medicines and vaccines, organizational efforts and purchase volumes have been pooled in joint procurements and negotiations for decades in some regions of the world, as well as globally through supranational procurement mechanisms. In Europe, countries started to collaborate on procurement and negotiations recently when it became increasingly difficult to ensure access to high-priced medicines, even in high-income countries. Two European country collaborations (the Nordic Pharmaceutical Forum and the Baltic Procurement Initiative) have successfully concluded at least one joint tender process for medicines and vaccines and the Beneluxa Initiative has concluded its first successful joint price negotiation. This article describes the experiences of these country collaborations. Challenges observed included: legal barriers; institutional and organizational differences between health-care systems in member countries; and the risk that suppliers will be reluctant to cooperate with country collaborations. Although these collaborations helped improve access to medicines and vaccines for the countries involved, in situations such as a global health crisis, larger-scale, more-inclusive initiatives are needed. In the current coronavirus disease 2019 (COVID-19) pandemic, COVID-19 Vaccines Global Access (COVAX) initiative established a global procurement mechanism to ensure the equitable distribution of COVID-19 vaccines globally. Despite differences in organization and scale, the European country collaborations and COVAX have some similarities: (i) their success depends on the increased purchasing power associated with pooled order volumes; (ii) expert knowledge and previous procurement experience is pooled; (iii) they perform other collaborative activities that go beyond procurement alone; and (iv) they actively involve external partners and stakeholders. [ABSTRACT FROM AUTHOR]

Driving under the influence of alcohol, drugs and fatigue are all important factors of crash causation. Exploring the link between driver attitudes and crash involvement provides understanding on these important issues. To that end, questionnaire answers of car drivers disclosing their attitudes on the impacts of driving under the influence of alcohol, drugs and fatigue, and their relationship with past crash involvement as car drivers were analysed. A two-step approach is adopted: Principal Component Analysis (PCA) was employed to consolidate relative questions in numeric factor quantities. Afterwards, binary logistic regression was implemented on the calculated component scores to determine the impact of perspectives of road users for each factor on past crash involvement of car drivers. Data from the international ESRA2015 survey were utilized. PCA indicated that it is possible to meaningfully merge 29 ESRA2015 questions relevant to driving under the influence of alcohol, drugs and fatigue into 8 informative components accounting for an adequate percentage of variance. Binary logistic analysis indicated that components involving overall personal and communal acceptance of impaired driving, overall and past year personal behaviour towards impaired driving and frequency of typical journey checks by traffic police were all quantities positively correlated with past crash involvement. [ABSTRACT FROM AUTHOR]

Background Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. Methods STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. Results The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. Conclusion STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies. [ABSTRACT FROM AUTHOR]

Background: Several new antidiabetic medicines (GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors) have been approved by the European Medicines Agency since 2006. The aim of this study was to evaluate the uptake of new antidiabetic medicines in European countries over a 10-year period. Methods: The study used IQVIA quarterly value and volume sales data January 2006–December 2016. The market uptake of new antidiabetic medicines together with intensity of prescribing policy for all antidiabetic medicines were estimated for Austria, Croatia, France, Germany, Hungary, Italy, Poland, Slovenia, Spain, Sweden, and the United Kingdom. The following measures were determined: number of available new active substances, median time to first continuous use, volume market share, and annual therapy cost. Results: All countries had at least one new antidiabetic medicine in continuous use and an increase in intensity of prescribing policy for all antidiabetic medicines was observed. A tenfold difference in median time to first continuous use (3–30 months) was found. The annual therapy cost in 2016 of new antidiabetic medicines ranged from EUR 363 to EUR 769. Among new antidiabetic medicines, the market share of DPP-4 inhibitors was the highest. Countries with a higher volume market share of incretin-based medicines (Spain, France, Austria, and Germany) in 2011 had a lower increase in intensity of prescribing policy. This kind of correlation was not found in the case of SGLT-2 inhibitors. Conclusions: This study found important differences and variability in the uptake of new antidiabetic medicines in the included countries. [ABSTRACT FROM AUTHOR]

Background The daily oral dosing requirement for antiretroviral therapy (ART) may be challenging for some people living with HIV (PLWHIV) with comorbid conditions, confidentiality concerns or pill fatigue. We investigated suboptimal adherence from the perspective of PLWHIV and HIV physicians. Methods PLWHIV on ART (n  = 688) and HIV physicians (n  = 120) were surveyed during 2019 in France, Germany, Italy and the UK. Suboptimal adherence was a report the participant missed taking their dose as prescribed 'Sometimes'/'Often'/'Very often'. Physicians' interest in offering a hypothetical long-acting HIV regimen for suboptimally adherent patients was assessed. Descriptive and multivariable analyses were performed (P  < 0.05). Results Of PLWHIV, 23.8% (164/688) reported suboptimal adherence vs. providers' estimated prevalence of 33.6% (SD = 28.8). PLWHIV-reported prevalence of specific suboptimal adherence behaviors were: mistimed dose [16.1% (111/688)]; missed a dose [15.7% (108/688)]; dosed under wrong conditions [e.g. food restrictions, 10.5% (72/688)] and overdosed [3.3% (23/688)]. Odds of suboptimal adherence were higher among those with vs. without a report of the following: dysphagia (AOR = 3.61, 95% CI = 2.28–5.74), stress/anxiety because of their daily dosing schedule (AOR = 3.09, 95% CI = 1.97–4.85), gastrointestinal side effects (AOR = 2.09, 95% CI = 1.39–3.15), neurocognitive/mental health conditions (AOR = 1.88, 95% CI = 1.30–2.72) or hiding their HIV medication (AOR = 1.51, 95% CI = 1.04–2.19). Of providers, 84.2% indicated they Definitely/Probably will offer a hypothetical long-acting HIV regimen 'for patients who have suboptimal levels of adherence to daily oral therapy (50–90%) for non-medical reasons'. Conclusions Dysphagia, stressful daily oral dosing schedule, gastrointestinal side effects, neurocognitive/mental health conditions and confidentiality concerns were associated with suboptimal adherence in our study. Adherence support and alternative regimens, such as long-acting antiretroviral therapies, could help address these challenges. [ABSTRACT FROM AUTHOR]

Affordable access to healthcare including medicines is a key social policy goal in Europe. However, it has rarely been addressed in comparative social policy research. Although the concept of decommodification has already been used in the context of healthcare and sickness benefits, we argue that the scope of such studies should be expanded to medicines to understand how welfare states protect their citizens from market forces in case of illness. We examine and compare the relationship between income, other characteristics, and subjective financial burden of medicines (FBM) across five countries with universal health systems pursuing egalitarian aims (Denmark, Finland, the Netherlands, Norway and Sweden). Analyses using 2017 EU-SILC microdata and linear probability models showed large differences in the level of FBM across countries, with the highest income quintile in Finland reporting FBM more frequently than the lowest income quintile in Denmark. Finland differed from the rest by increasing probability of FBM with age. In other countries, middle-aged adults tended to be the most affected, and older adults were well-protected. The association between income and FBM was strongest in the Netherlands; however, the higher probability of FBM was skewed towards the lower quintiles in all countries. FBM and financial burden of medical care were strongly associated although FBM tended to be more common. Unmet needs for medical examination were rare and lacked sensitivity in capturing manifestations of market risk. Decommodification literature has focused healthcare services as proxy of access; nevertheless, our study shows that further functions, and broader outcomes should be examined to capture market risk. Our evidence further highlights that important differences can be found even in countries with relatively similar health policy aims. The cost of medicines should be considered in comparative studies of health and welfare states. • Access to medicines should be considered in studies of decommodification. • Market risk manifested predominantly as subjective financial burden. • Significant country differences in financial burden were found. [ABSTRACT FROM AUTHOR]

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables. [ABSTRACT FROM AUTHOR]

Objective: People's socioeconomic status (SES) has a major impact on the risk of atherosclerotic cardiovascular disease (ASCVD) in primary prevention. In patients with existing ASCVD these associations are less documented. Here, we evaluate to what extent SES is still associated with patients' risk profile in secondary prevention.Methods: Based on results from a large sample of patients with coronary heart disease from the European Action on Secondary and Primary Prevention through Intervention to Reduce Events study, the relationship between SES and cardiovascular risk was examined. A SES summary score was empirically constructed from the patients' educational level, self-perceived income, living situation and perception of loneliness.Results: Analyses are based on observations in 8261 patients with coronary heart disease from 27 countries. Multivariate logistic regression analyses demonstrate that a low SES is associated (OR, 95% CI) with lifestyles such as smoking in men (1.63, 1.37 to 1.95), physical activity in men (1.51, 1.28 to 1.78) and women (1.77, 1.32 to 2.37) and obesity in men 1.28 (1.11 to 1.49) and women 1.65 (1.30 to 2.10). Patients with a low SES have more raised blood pressure in men (1.24, 1.07 to 1.43) and women (1.31, 1.03 to 1.67), used less statins and were less adherent to them. Cardiac rehabilitation programmes were less advised and attended by patients with a low SES. Access to statins in middle-income countries was suboptimal leaving about 80% of patients not reaching the low-density lipoprotein cholesterol target of <1.8 mmol/L. Patients' socioeconomic level was also strongly associated with markers of well-being.Conclusion: These results illustrate the complexity of the associations between SES, well-being and secondary prevention in patients with ASCVD. They emphasise the need for integrating innovative policies in programmes of cardiac rehabilitation and secondary prevention. [ABSTRACT FROM AUTHOR]

Based on research undertaken as part of the EU funded EPPIC project, this paper aims to update and elaborate on the relationship between drug use and offending behaviours by exploring variations within a cross-national sample of drug-experienced young people in touch with criminal justice systems. Adopting a trajectory-based approach, interviews were undertaken with 198 young people aged 15–25 in six European countries (Austria, Denmark, Germany, Italy, Poland, and UK). Data were analysed by applying the Bennett and Holloway categorization of the drugs-crime link, with a focus on the concept of social exclusion as developed by Seddon. Three main types of mechanisms (economic, pharmaceutical, and lifestyles) are used to interpret the data, showing how the relationship between drugs and offending can vary according to type of substances and over time. Furthermore, it can be associated with very different degrees of social exclusion and needs. The results suggest that while economic inequalities still play key roles in explaining drug use and offending, both behaviours can originate from a state of relative deprivation, resulting from the contradictions inherent in 'bulimic societies' that raise aspirations and desires while providing young people scarce opportunities for self-realisation and social recognition. [ABSTRACT FROM AUTHOR]

The safety of switching between generic products of antiseizure medications (ASMs) continues to be a hot topic in epilepsy management. The main reason for concern relates to the uncertainty on whether, and when, two generics found to be bioequivalent to the same brand (reference) product are bioequivalent to each other, and the risk of a switch between generics resulting in clinically significant changes in plasma ASM concentrations. This article addresses these concerns by discussing the distinction between bioequivalence and statistical testing for significant difference, the importance of intra‐subject variability in interpreting bioequivalence studies, the stricter regulatory bioequivalence requirements applicable to narrow‐therapeutic‐index (NTI) drugs, and the extent by which currently available generic products of ASMs comply with such criteria. Data for 117 oral generic products of second‐generation ASMs approved in Europe by the centralized, mutual recognition or decentralized procedure were analyzed based on a review of publicly accessible regulatory assessment reports. The analysis showed that for 99% of generic products assessed (after exclusion of gabapentin products), the 90% confidence intervals (90% CIs) of geometric mean ratios (test/reference) for AUC (area under the drug concentration vs time curve) were narrow and wholly contained within the acceptance interval (90%–111%) applied to NTI drugs. Intra‐subject variability for AUC was <10% for 53 (88%) of the 60 products for which this measure was reported. Many gabapentin generics showed broader, 90% CIs for bioequivalence estimates, and greater intra‐subject variability, compared with generics of other ASMs. When interpreted within the context of other available data, these results suggest that any risk of non‐bioequivalence between these individual generic products is small, and that switches across these products are not likely to result in clinically relevant changes in plasma drug exposure. The potential for variability in exposure when switching across generics is likely to be greatest for gabapentin. [ABSTRACT FROM AUTHOR]

Background: Inclusion of productivity losses and gains in cost-effectiveness analyses for drugs is recommended by pharmacoeconomic guidelines in some countries and is considered optional in others. Often guidelines recommend analysis based on the payer perspective, but suggest that a supplemental analysis based on the societal perspective may be submitted that includes productivity losses/gains. However, there is no universally recognized framework for the approach to including productivity losses and gains in pharmacoeconomic analyses.Objectives: This study aimed to systematically review literature on cost-effectiveness analyses of drug interventions that included costs associated with productivity losses/gains and to summarize the types cost elements included and cost calculation methods employed. Moreover, this study examines variations in the calculation of productivity losses/gains by target disease type, geographic region, income group, period of analysis, and analysis time horizon-as well as the impact of their inclusion on the study outcomes.Methods: A search of three databases was performed, including MEDLINE, Embase, and the Cochrane Library, to identify cost-effectiveness and cost-utility analyses that included indirect costs such as productivity losses/gains. Publications from January 2010 to October 2019 were examined and selected for inclusion by two independent reviewers. In addition to the citation details, data on the country of analysis, country income group, target disease area, study sponsorship, type of analysis, study design, time horizon, analysis perspective, productivity loss/gain elements included, the approach used to estimate productivity losses/gains, and the impact of their inclusion on the study outcome-namely the incremental cost effectiveness ratio-were extracted and summarized.Results: The search strategy identified 5038 unique studies, and 208 were included in the final analysis. Among the studies reviewed, 165 (79%) were conducted in high-income countries and 160 (77%) were conducted for North American and European/Central Asian countries. The productivity loss/gain elements included in the analysis were reported for 169 studies (81%). Absenteeism only was included for 98 studies (47%), and absenteeism plus presenteeism was included for 29 studies (14%). Absenteeism plus some other element such as costs associated with unemployment and/or early retirement was included for 32 studies (15%) examined. Only one out of four of the studies reviewed included information on the approach used to estimate productivity losses/gains, which was predominantly the human capital approach. One-hundred forty-four studies (69%) reported the impact of including productivity losses/gains on the ICER, with 110 studies (53%) reporting that their inclusion contributed to more favorable cost-effectiveness.Conclusions: Although inclusion of productivity losses/gains was shown to have a favorable impact on evaluations for many studies, their impact and method of calculation was often not reported or was unclear. Further examination and discussion is needed to consider the optimal framework for considering productivity losses/gains in cost-effectiveness analyses, including the appropriate cost elements to include (e.g., patient absenteeism, caregiver absenteeism, presenteeism, unemployment, etc.) and how those costs should be estimated. [ABSTRACT FROM AUTHOR]

Objective: To establish European League Against Rheumatism (EULAR) points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older.Methods: Points to consider were developed in accordance with EULAR standard operating procedures for EULAR-endorsed recommendations, led by an international multidisciplinary task force, including patient research partners and different health professionals from 10 European countries. Level of evidence and strength of recommendation were determined for each point to consider, and the mean level of agreement among the task force members was calculated.Results: Two overarching principles and seven points to consider were formulated based on scientific evidence and the expert opinion of the task force. The two overarching principles focus on shared decisions between patients and non-physician health professionals and involvement of different non-physician health professionals in prevention and management of fragility fractures. Four points to consider relate to prevention: identification of patients at risk of fracture, fall risk evaluation, multicomponent interventions to prevent primary fracture and discouragement of smoking and overuse of alcohol. The remaining three focus on management of fragility fractures: exercise and nutritional interventions, the organisation and coordination of multidisciplinary services for post-fracture models of care and adherence to anti-osteoporosis medicines. The mean level of agreement among the task force for the overarching principles and the points to consider ranged between 8.4 and 9.6.Conclusion: These first EULAR points to consider for non-physician health professionals to prevent and manage fragility fractures in adults 50 years or older serve to guide healthcare practice and education. [ABSTRACT FROM AUTHOR]

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Methods: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization.Results: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36).Conclusions: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800. [ABSTRACT FROM AUTHOR]

What is known and objective: The real‐life prognostic impact on long‐term survival of continuous or discontinuous adherence to ESC guideline‐recommended drugs in heart failure with reduced ejection fraction (HFrEF) patients has rarely been investigated. Here, we present the long‐term association of longitudinal prescription of guideline‐recommended drugs with 3‐year all‐cause and cardiovascular (CV) mortality in HFrEF patients. Methods: We used data from the EPICAL2 cohort study of 624 hospitalized HFrEF patients. Using the sequence analysis, we classified patients into five groups of long‐term adherence according to the continuity/discontinuity of their prescription adherence to guidelines over a 3‐year follow‐up, as follow: 316 (50.6%) patients in the sustained adherence group, 163 (26.1%) in the sustained non‐adherence group, 79 (12.6%) in the adherence to non‐adherence group, 43 (6.9%) in the non‐adherence to adherence group and 23 (3.7%) in the multiple switches group. The associations between all‐cause mortality and CV mortality and the adherence groups were determined by Cox and Fine‐Gray models, respectively. To account for immortal time bias, we performed a landmark analysis at 24 months. Patients who died, prior to the landmark time, were excluded from this analysis and long‐term adherence groups were redefined. Results and discussion: After adjustment for confounding factors, as compared to the sustained non‐adherence group, the sustained adherence group showed lower all‐cause and CV mortality (hazard ratio HR = 0.37 [0.25‐0.56] and sub‐distribution hazard ratio SHR = 0.33 [0.20‐0.56]). Both clinical outcomes were also significantly improved in the adherence to non‐adherence group (HR = 0.25 [0.13‐0.45] and SHR = 0.20 [0.10‐0.41]), the non‐adherence to adherence (HR = 0.24 [0.11‐0.55] and SHR = 0.11 [0.04‐0.30]), and for the multiple switches group (HR = 0.13 [0.07‐0.51] and SHR = 0.12 [0.08‐0.43]). Results from landmark analysis were comparable to the main results. What is new and conclusion: As in all observational studies, our results may be affected by residual confounding related to unmeasured confounders, although we attempted to adjust for many confounders. Even a discontinuous prescription of the recommended drugs over time was associated with better long‐term outcomes. In other words, whatever the time of HFrEF evolution, prescribing recommended drugs at some point was always better than never prescribing. [ABSTRACT FROM AUTHOR]

The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak. [ABSTRACT FROM AUTHOR]

Aims: Open drug scenes can be found in most major cities in Europe. Despite often being closed down by the police, the drug community continues to exist, and the drug scenes reappear elsewhere. There seem to be forces that hold these communities together, regardless of the substances used. In this study we explore whether interaction rituals have an impact on the decision by people to stay in the drug scene or to return after quitting their drug use. Method: In this ethnographic study, one of the researchers spent time in an open drug scene in a Norwegian city over a one-year span and gathered data on the human interactions hosted by this scene. In addition, the researcher interviewed eight people from the scene to obtain greater insight into their lives and perceptions of the scene, drawing on Goffman's and Collins's theories about rituals. Findings: Three themes emerged. First, drug users bonded as a group and resisted what they called "normal people" passing by. Second, users demonstrated the importance of sharing drugs and services and adhering to the scene's rules of conduct. The third and final theme is the focus of attention and the production of emotional energy. Conclusion: The experience of being outsiders and the need to hide some of their activities seemed to make it necessary for persons in the drug scene to have their own rules and rituals. These rules and rituals can be regarded as "interaction rituals". They provide participants with the symbols of group membership, emotional energy, and group solidarity. This makes it hard to leave the scene and might explain why those who do often return. [ABSTRACT FROM AUTHOR]

Repurposing of medicines has gained a lot of interest from the research community in recent years as it could offer safe, timely, and affordable new treatment options for cancer patients with high unmet needs. Increasingly, questions arise on how new uses will be translated into clinical practice, especially in case of marketed medicinal products that are out of basic patent or regulatory protection. The aim of this study was to portray the regulatory framework relevant for making repurposed medicines available to cancer patients in Europe and propose specific policy recommendations to address the current regulatory and financial barriers. We outlined two routes relevant to the clinical adoption of a repurposed medicine. First, a new indication can be approved, and thus brought on-label, via the marketing authorization procedures established in European and national legislation. Such procedures initiate a detailed and independent assessment of the quality and the benefit-risk balance of a medicinal product in a specific indication, benefiting both prescribers and patients as it reassures them that the scientific evidence is robust. However, the process of marketing authorization for new therapeutic indications entails a high administrative burden and significant costs while the return-on-investment for the pharmaceutical industry is expected to be low or absent for medicines that are out of basic patent and regulatory protection. Moreover, most of the repurposing research is conducted by independent or academic researchers who do not have the expertise or resources to get involved in regulatory procedures. A second option is to prescribe a medicine off-label for the new indication, which is managed at the national level in Europe. While off-label use could provide timely access to treatments for patients with urgent medical needs, it also entails important safety, liability and financial risks for patients, physicians, and society at large. In view of that, we recommend finding solutions to facilitate bringing new uses on-label, for example by developing a collaborative framework between not-for-profit and academic organizations, pharmaceutical industry, health technology assessment bodies, payers, and regulators. [ABSTRACT FROM AUTHOR]

The Integrated Management of Childhood Illness (IMCI) was introduced in Central Asia and Europe to address the absence of evidence-based guidelines, antibiotics misuse, polypharmacy and overhospitalisation. This study in 16 countries analyses status, strengths of and barriers to IMCI implementation and investigates how health systems affect the problems IMCI aims to address. 220 key informants were interviewed ranging from 5 to 37 per country (median 12). Data were analysed for arising themes and peer-reviewed. IMCI has not been fully used either as a strategy or as an algorithmic diagnostic and treatment decision tool. Inherent incentives include: economic factors taking precedence over evidence and the best interest of the child in treatment decisions; financing mechanisms and payment schemes incentivising unnecessary or prolonged hospitalisation; prescription of drugs other than IMCI drugs for revenue generation or because believed superior by doctors or parents; parents' perception that the quality of care at the primary healthcare level is poor; preference for invasive treatment and medicalised care. Despite the long-standing recognition that supportive health systems are a requirement for IMCI implementation, efforts to address health system barriers have been limited. Making healthcare truly universal for children will require a shift towards health systems designed around and for children and away from systems centred on providers' needs and parents' expectations. Prerequisites will be sufficient remuneration, sound training, improved health literacy among parents, conducive laws and regulations and reimbursement systems with adequate checks and balances to ensure the best possible care. [ABSTRACT FROM AUTHOR]