Mechanical properties of a biodegradable self-expandable polydioxanone monofilament stent: In vitro force relaxation and its clinical relevance

Biodegradable stents are promising treatments for many diseases, e.g., coronary artery disease, urethral diseases, tracheal diseases, and esophageal strictures. The mechanical properties of biodegradable stent materials play a key role in the safety and efficacy of treatment. In particular, insufficient creep resistance of the stent material could result in premature stent collapse or narrowing. Commercially available biodegradable self-expandable SX-ELLA stents made of polydioxanone monofilament were tested. A new, simple, and affordable method to measure the shear modulus of tiny viscoelastic wires is presented. The important mechanical parameters of the polydioxanone filament were obtained: the median Young's modulus was (E) over tilde = 958 (922, 974) MPa and the shear modulus was (G) over tilde= 357 (185, 387) MPa, resulting in a Poisson's ratio of nu = 0.34. The SX-ELLA stents exhibited significant force relaxation due to the stress relaxation of the polydioxanone monofilament, approximately 19% and 36% 10 min and 48 h after stent application, respectively. However, these results were expected, and the manufacturer and implanting clinician should be aware of the known behavior of these biodegradable materials. If possible, a biodegradable stent should be designed considering therapeutic force rather than initial force. Additionally, new and more advanced biodegradable shape-memory polymers should be considered for future study and use

Comparison of drug prescribing before and during the COVID‐19 pandemic : a cross‐national European study

Purpose: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. Methods: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. Results: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from −39.4% in Romagna to −14.2% in Scotland) and nasal preparations (from −34.4% in Lithuania to −5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. Conclusions: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas

Corrigendum to "Utilisation trend of long-acting insulin analogues including biosimilars across Europe: findings and implications"

In the article titled "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications" [1], the captions of Figures 3 and 4 were incorrect. The corrected captions for Figures 3 and 4 appear below

Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments

Clinicopathological Characteristics and Prognostic Factors in Ovarian Metastases from Right- and Left-Sided Colorectal Cancer

Background: Secondary tumors of the ovary (STOs) account for 10–25% of all ovarian malignancies, including metastases from primary gynecological tumors. Colorectal cancer (CRC) has been recognized as one of the most common causes of STOs in Western countries. Despite it being well-known that CRC originating from the right versus left side of the colon/rectum differ substantially, there is a paucity of information regarding the effect of the primary tumor sidedness on the clinicopathological characteristics of STOs. Methods: This retrospective, observational chart review study included patients with histologically confirmed STOs of CRC origin diagnosed between January 2000 and December 2019. The clinicopathological characteristics of STOs originating from left-sided and right-sided CRC were compared. Univariable and multivariable analyses employing elastic net Cox proportional hazard models were used to evaluate potential prognostic factors. Further, the role of imaging methods in STOs diagnostics was evaluated. Results: Fifty-one patients with STOs of colorectal origin were identified. The primary tumor originated in the right and left colon/rectum in 39% and 61% of the cases, respectively. STOs originating from right-sided primary tumors were more frequently bilateral, associated with peritoneal carcinomatosis, had the ovarian surface affected by the tumor, and contained a mucinous component. The independent prognostic factors for overall survival in the whole cohort included: the presence of macroscopic residual disease after cytoreductive surgery, menopausal status, the application of systemic therapy, and the application of targeted therapy. In 54% of cases, the imaging methods failed to determine the laterality of the STOs correctly as compared to pathological reports and/or intraoperative findings. Conclusion: STOs originating from left-sided and right-sided CRC show distinct clinicopathological characteristics. Moreover, different metastatic pathways might be employed according to the primary tumor sidedness. Considering the discrepancies between radiological assessment and histopathological findings regarding the laterality of STOs, bilateral adnexectomy should be advised whenever feasible

Can Aspartate Aminotransferase in the Cerebrospinal Fluid Be a Reliable Predictive Parameter?

Brain ischemia after central nervous system (CNS) bleeding significantly influences the final outcome of patients. Catalytic activities of aspartate aminotransferase (AST) in the cerebrospinal fluid (CSF) to detect brain ischemia were determined in this study. The principal aim of our study was to compare the dynamics of AST in 1956 CSF samples collected from 215 patients within a 3-week period after CNS hemorrhage. We compared concentrations of the AST catalytic activities in the CSF of two patient groups: survivors (Glasgow Outcome Score (GOS) 5–3) and patients in a vegetative state or dead (GOS 2–1). All statistical evaluations were performed using mixed models and the F-test adjusted by Kenward and Roger and the Bonferroni adjustment for multiple tests. The significantly higher catalytic activities of AST in the CSF from patients with the GOS of 2–1 when compared to those who survived (GOS 5–3, p = 0.001) were found immediately after CNS haemorrhage. In the further course of time, the difference even increased (p < 0.001). This study confirmed the key association between early signs of brain damage evidenced as an elevated AST activity and the prediction of the final patient’s clinical outcome. The study showed that the level of AST in the CSF could be the relevant diagnostic biomarker of the presence and intensity of brain tissue damage

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe : Findings and Implications

Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed

Utilisation trend of long-acting insulin analogues including biosimilars across Europe : findings and implications

Background. Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Results. Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. Conclusions. There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems. Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines. Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments