Usage and impact of patient-reported outcomes in epilepsy.

BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.

New pricing models for generic medicines to ensure long-term sustainable competition in Europe.

Background: Price erosion of generic medicines over time as a result of existing pricing policies in combination with increasing operational costs of these products due to high inflation, undermine long-term sustainable competition in European off-patent medicines markets. Therefore, the aim of this study is to identify new potential pricing models for retail generic medicines in Europe, examine their pros and cons, and illustrate them with examples inside or outside the pharmaceutical sector. Methods: A targeted literature review, one-to-one interviews and a joint advisory board meeting with experts from five European countries were carried out to assess potential pricing models for generic medicines. Results: We identified ten pricing models that can be applied to generic medicines. The tiered pricing model is viewed as a sustainable solution ensuring competitiveness, but requires market monitoring using a supportive IT infrastructure. De-linking the price of generic medicines from that of the off-patent originator medicine prevents the originator from forcing generic medicines' prices to unsustainable levels. Higher costs due to inflation can be compensated in the automatic indexation model. Other pricing models that have less implementation potential include the one-in-one/multiple-out model, tax credits, value-based pricing, volume for savings and guaranteed margin/fee models. The hypothecated tax and cost allocation models, which add a patient fee to generic medicines prices, are not likely to be socially acceptable. Conclusion: When considering a new pricing model for generic medicines, the impact on innovative medicines and the characteristics of the healthcare system in a given country need to be taken into account. Also, there is a need to continuously follow up the level of competition in off-patent medicines markets and to identify sustainability risks.

An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus.

Enterococcus species are known for their ability to form biofilms, which contributes to their survival in extreme environments and involvement in persistent bacterial infections, especially in the case of multi-drug-resistant strains. This review aims to provide a comprehensive understanding of the mechanisms underlying biofilm formation in clinically important species such as Enterococcus faecalis and the less studied but increasingly multi-drug-resistant Enterococcus faecium, and explores potential strategies for their eradication. Biofilm formation in Enterococcus involves a complex interplay of genes and virulence factors, including gelatinase, cytolysin, Secreted antigen A, pili, microbial surface components that recognize adhesive matrix molecules (MSCRAMMs), and DNA release. Quorum sensing, a process of intercellular communication, mediated by peptide pheromones such as Cob, Ccf, and Cpd, plays a crucial role in coordinating biofilm development by targeting gene expression and regulation. Additionally, the regulation of extracellular DNA (eDNA) release has emerged as a fundamental component in biofilm formation. In E. faecalis, the autolysin N-acetylglucosaminidase and proteases such as gelatinase and serin protease are key players in this process, influencing biofilm development and virulence. Targeting eDNA may offer a promising avenue for intervention in biofilm-producing E. faecalis infections. Overall, gaining insights into the intricate mechanisms of biofilm formation in Enterococcus may provide directions for anti-biofilm therapeutic research, with the purpose of reducing the burden of Enterococcus-associated infections.

A review of the sustainability of vaccine funding across Europe and implications for post-COVID policymaking.

BACKGROUND: Approaches to routine vaccine funding and the underlying budget-setting process vary greatly across European countries. The ongoing COVID-19 pandemic has put enormous pressure on healthcare systems, affecting resilience of the overall vaccine ecosystem. METHODS: This article reviews how vaccine budgets are structured across 8 European countries (England, Finland, France, Germany, Italy, Norway, Romania, and Spain). First a literature review of the landscape was undertaken, followed by expert interviews to review the findings and consider policy principles to secure prioritisation and sustainability of routine vaccination budgets post-COVID. RESULTS: The organisation of budgets and vaccine spending varies greatly across Europe. In 2/8 countries (France and Germany) vaccine spending is subsumed into a wider healthcare budget. In 2/8 countries (Italy and Romania) the budget differentiates public health and prevention spending from other areas of healthcare, though there is no standalone vaccine budget. In 4/8 countries (England, Finland, Norway and Spain) there is a standalone vaccine budget, however this may not cover all elements needed for immunisation delivery and is not always transparent. CONCLUSION: Ensuring adequate and dynamic country vaccine budgets, with horizon scanning approaches like in England and Finland, or flexible vaccines expenditures like Germany, would greatly help the timely availability of public funding for new vaccines and strengthen vaccines supply security in Europe through a more virtuous European vaccine ecosystem.

Death by SARS-CoV 2: a Romanian COVID-19 multi-centre comorbidity study.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Burden of influenza in Romania. A retrospective analysis of 2014/15 - 2018/19 seasons in Romania.

INTRODUCTION: Influenza is a seasonal epidemic with a heavy negative impact both on population health, and healthcare system utilization; until now, there are only two burden of disease studies in the Romanian context. This study aims to quantify the burden of influenza for the Romanian population for the seasons 2014/15 to 2018/19, using health administrative databases. METHODS: Incidence, hospitalization and mortality rates attributable to influenza as well as total number of influenza cases and deaths were estimated, for each season in the analyzed period, by combining the new cases reported by General Practitioners, Emergency Department presentations, hospitalizations, number of deaths, positivity rate of influenza, and probability to be consulted by a physician. Years of life lost due to premature death attributable to influenza complications were also computed. RESULTS: On average, 591,151 cases/season attributable to influenza were estimated during the period 2014/15 - 2018/19. The highest rates for incidence, hospitalization and presentation to emergency department were found in the age groups 0-4 years and 65 years and above. Influenza mortality rate was estimated at 3 per 100,000 persons and the 65 and above age group had the highest rate. CONCLUSIONS: About 3% of the total Romanian population is estimated to develop an influenza attributable disease in a non-pandemic season. An overall increasing trend of the mortality rate attributable to influenza may be also underlined. On average, a person loses 12 years due to premature death caused by complications of influenza.

Changes in disease burden in Poland between 1990-2017 in comparison with other Central European countries: A systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Systematic collection of mortality/morbidity data over time is crucial for monitoring trends in population health, developing health policies, assessing the impact of health programs. In Poland, a comprehensive analysis describing trends in disease burden for major conditions has never been published. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides data on the burden of over 300 diseases in 195 countries since 1990. We used the GBD database to undertake an assessment of disease burden in Poland, evaluate changes in population health between 1990-2017, and compare Poland with other Central European (CE) countries. METHODS: The results of GBD 2017 for 1990 and 2017 for Poland and CE were used to assess rates and trends in years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs). Data came from cause-of-death registration systems, population health surveys, disease registries, hospitalization databases, and the scientific literature. Analytical approaches have been used to adjust for missing data, errors in cause-of-death certification, and differences in data collection methodology. Main estimation strategies were ensemble modelling for mortality and Bayesian meta-regression for disability. RESULTS: Between 1990-2017, age-standardized YLL rates for all causes declined in Poland by 46.0% (95% UI: 43.7-48.2), YLD rates declined by 4.0% (4.2-4.9), DALY rates by 31.7% (29.2-34.4). For both YLLs and YLDs, greater relative declines were observed for females. There was a large decrease in communicable, maternal, neonatal, and nutritional disease DALYs (48.2%; 46.3-50.4). DALYs due to non-communicable diseases (NCDs) decreased slightly (2.0%; 0.1-4.6). In 2017, Poland performed better than CE as a whole (ranked fourth for YLLs, sixth for YLDs, and fifth for DALYs) and achieved greater reductions in YLLs and DALYs than most CE countries. In 2017 and 1990, the leading cause of YLLs and DALYs in Poland and CE was ischaemic heart disease (IHD), and the leading cause of YLDs was low back pain. In 2017, the top 20 causes of YLLs and YLDs in Poland and CE were the same, although in different order. In Poland, age-standardized DALYs from neonatal causes, other cardiovascular and circulatory diseases, and road injuries declined substantially between 1990-2017, while alcohol use disorders and chronic liver diseases increased. The highest observed-to-expected ratios were seen for alcohol use disorders for YLLs, neonatal sepsis for YLDs, and falls for DALYs (3.21, 2.65, and 2.03, respectively). CONCLUSIONS: There was relatively little geographical variation in premature death and disability in CE in 2017, although some between-country differences existed. Health in Poland has been improving since 1990; in 2017 Poland outperformed CE as a whole for YLLs, YLDs, and DALYs. While the health gap between Poland and Western Europe has diminished, it remains substantial. The shift to NCDs and chronic disability, together with marked between-gender health inequalities, poses a challenge for the Polish health-care system. IHD is still the leading cause of disease burden in Poland, but DALYs from IHD are declining. To further reduce disease burden, an integrated response focused on NCDs and population groups with disproportionally high burden is needed.

Data from numerical analysis, simulation and experimental determinations performed to verify the sizing of an unbalanced capacitive compensator for three-phase four-wires networks.

In a three-phase four-wire distribution network, the load unbalance can be compensated by the use of an unbalanced three-phase reactive compensator, containing six single-phase coils and capacitors, grouped into two distinct circuits, having Yn and delta connections. In (Pana et al., 2020) is presented a method of calculating the equivalent susceptances of the six reactive elements, so that they are capacitive or null. The paper demonstrates that a power factor improvement and a total or partial balancing of an unbalanced inductive load can be achieved by using an unbalanced capacitive compensator. The calculation method can be implemented in the control system of a SVC containing only single-phase capacitor banks. In this DiB article are presented additional data and information, obtained by numerical analysis, simulation-modeling and experimental determinations performed with the purpose of validation of the calculation method proposed in (Pana et al., 2020).

Oscillatory Cortical Activity in an Animal Model of Dystonia Caused by Cerebellar Dysfunction.

The synchronization of neuronal activity in the sensorimotor cortices is crucial for motor control and learning. This synchrony can be modulated by upstream activity in the cerebello-cortical network. However, many questions remain over the details of how the cerebral cortex and the cerebellum communicate. Therefore, our aim is to study the contribution of the cerebellum to oscillatory brain activity, in particular in the case of dystonia, a severely disabling motor disease associated with altered sensorimotor coupling. We used a kainic-induced dystonia model to evaluate cerebral cortical oscillatory activity and connectivity during dystonic episodes. We performed microinjections of low doses of kainic acid into the cerebellar vermis in mice and examined activities in somatosensory, motor and parietal cortices. We showed that repeated applications of kainic acid into the cerebellar vermis, for five consecutive days, generate reproducible dystonic motor behavior. No epileptiform activity was recorded on electrocorticogram (ECoG) during the dystonic postures or movements. We investigated the ECoG power spectral density and coherence between motor cortex, somatosensory and parietal cortices before and during dystonic attacks. During the baseline condition, we found a phenomenon of permanent adaptation with a change of baseline locomotor activity coupled to an ECoG gamma band increase in all cortices. In addition, after kainate administration, we observed an increase in muscular activity, but less signs of dystonia together with modulations of the ECoG power spectra with an increase in gamma band in motor, parietal and somatosensory cortices. Moreover, we found reduced coherence in all measured frequency bands between the motor cortex and somatosensory or parietal cortices compared to baseline. In conclusion, examination of cortical oscillatory activities in this animal model of chronic dystonia caused by cerebellar dysfunction reveals a disruption in the coordination of neuronal activity across the cortical sensorimotor/parietal network, which may underlie motor skill deficits.

Country-specific costs of implementing the WHO FCTC tobacco control policies and potential financing sources.

BACKGROUND: One of the major obstacles to the full implementation of the World Health Organization (WHO) Framework Convention of Tobacco Control (FCTC) tobacco control measures is the lack of sustainable financing resources. GOAL: To update and simulate country-specific indicators that are highly relevant to the costs and financial resources of the treaty policy implementation. We also developed an Excel tool for simulation and assessed the aggregated-level indicators by the 2016 World Bank income groups. APPROACHES: Using mostly 2016 data or 2014-15 data if 2016 one are not available, we updated five indicators relevant to the treaty implementation, which are the gap between current and desirable policy implementation, cigarette affordability, the costs of implementing best- buy tobacco control policies, the number of smoking-attributable deaths, and the simulated tax revenue resulting from a $1 tax increase. We also aggregated indicators and simulation results by the World Bank income groups, encompassing the five indicators and the reduction in smoking and in attributable deaths due to a hypothetical 1I$ tax increase. Finally, the policy implementation cost was compared with tax revenue and revenue increases. FINDINGS: As of 2016, smoking remains one of the leading causes of premature deaths worldwide while the implementation of best-buy tobacco control policies was below the recommended levels. Meanwhile, there was room to further increase cigarette taxes and prices, as cigarettes remained affordable in many countries. The total costs of implementing best-buy policies in the next 15 years merely account for 8.3% of the 2016 excise tax revenue, indicating that a small proportion of annual tax revenue could fund the implementation of tobacco control policies recommended by the WHO FCTC. CONCLUSIONS: Increasing taxes could have a multiplier impact on curbing tobacco use through aiding the implementation of the WHO FCTC.

Romanian medicine, European medicine.

The aim of the present paper is to present the message transmitted by the Presidential Lecture given during the first congress of arthroscopy organised in Romania, in March 2016, by the Romanian Society of Arthroscopy and Sports Trauma (SRATS). The goal was to present the evolution of medical care in Romania over the years, with the remarkable progress made in the first half of the twentieth century and the current status of arthroscopic surgery as seen from the point of view of medical professionals, as well as from a governmental point of view.