Search

Presents a regulatory perspective on making a therapeutic choice for anti-hemophilic factors in Europe. Rationale for the absence of recommendation between recombinant and plasma-derived factor VII/IX; Evaluation of the benefit-risk ratio when granting a marketing authorization; Viral safety and health issues.

Abstract: The studies on anthropogenic climate change performed in the last decade over Europe show consistent projections of increases in temperature and different patterns of precipitation with widespread increases in northern Europe and decreases over parts of southern and eastern Europe. In many countries and in recent years there is a tendency towards cereal grain yield stagnation and increased yield variability. Some of these trends may have been influenced by the recent climatic changes over Europe. A set of qualitative and quantitative questionnaires on perceived risks and foreseen impacts of climate and climate change on agriculture in Europe was distributed to agro-climatic and agronomy experts in 26 countries. Europe was divided into 13 Environmental Zones (EZ). In total, we had 50 individual responses for specific EZ. The questionnaires provided both country and EZ specific information on the: (1) main vulnerabilities of crops and cropping systems under present climate; (2) estimates of climate change impacts on the production of nine selected crops; (3) possible adaptation options as well as (4) adaptation observed so far. In addition we focused on the overall awareness and presence of warning and decision support systems with relevance for adaptation to climate change. The results show that farmers across Europe are currently adapting to climate change, in particular in terms of changing timing of cultivation and selecting other crop species and cultivars. The responses in the questionnaires show a surprisingly high proportion of negative expectations concerning the impacts of climate change on crops and crop production throughout Europe, even in the cool temperate northern European countries. The expected impacts, both positive and negative, are just as large in northern Europe as in the Mediterranean countries, and this is largely linked with the possibilities for effective adaptation to maintain current yields. The most negative effects were found for the continental climate in the Pannonian zone, which includes Hungary, Serbia, Bulgaria and Romania. This region will suffer from increased incidents of heat waves and droughts without possibilities for effectively shifting crop cultivation to other parts of the years. A wide range of adaptation options exists in most European regions to mitigate many of the negative impacts of climate change on crop production in Europe. However, considering all effects of climate change and possibilties for adaptation, impacts are still mostly negative in wide regions across Europe. [Copyright &y& Elsevier]

Climate change and global warming have contributed to increase terrestrial drought, causing negative impacts on agricultural production. Drought stress may be addressed using novel agronomic practices and beneficial soil microorganisms, such as arbuscular mycorrhizal fungi (AMF), able to enhance plant use efficiency of soil resources and water and increase plant antioxidant defence systems. Specific traits functional to plant resilience improvement in dry conditions could have developed in AMF growing in association with xerophytic plants in maritime sand dunes, a drought-stressed and low-fertility environment. The most studied of such plants are European beachgrass (Ammophila arenaria Link), native to Europe and the Mediterranean basin, and American beachgrass (Ammophila breviligulata Fern.), found in North America. Given the critical role of AMF for the survival of these beachgrasses, knowledge of the composition of AMF communities colonizing their roots and rhizospheres and their distribution worldwide is fundamental for the location and isolation of native AMF as potential candidates to be tested for promoting crop growth and resilience under climate change. This review provides quantitative and qualitative data on the occurrence of AMF communities of A. arenaria and A. breviligulata growing in European, Mediterranean basin and North American maritime sand dunes, as detected by morphological studies, trap culture isolation and molecular methods, and reports on their symbiotic performance. Moreover, the review indicates the dominant AMF species associated with the two Ammophila species and the common species to be further studied to assess possible specific traits increasing their host plants resilience toward drought stress under climate change., (© 2024. The Author(s).)

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research., (© 2023 International Society of Blood Transfusion.)

Introduction: Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system., Areas Covered: Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management., Expert Opinion: Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.

Plasma-derived medicinal products (PDMPs) are life-saving and life-improving therapies, but the raw material is in short supply: Europe depends on importation from countries including the United States. Plasma from donors resident in the United Kingdom has not been fractionated since 1999 when a precautionary measure was introduced in response to the outbreak of variant Creutzfeldt-Jakob disease (vCJD). Cases of vCJD have been far fewer than originally predicted in the 1990s. Since the introduction of leucodepletion in 1999, and accounting for the incubation period, more than 40 million UK-derived blood components have been issued with no reports of TT vCJD. In February 2021, the UK Government authorized manufacture of immunoglobulin from UK plasma. Following separate reviews concluding no significant difference in the risk posed, the United States, Australia, Ireland and Hong Kong also lifted their deferrals of blood donors with a history of living in the United Kingdom. Other countries are actively reviewing their position. Demand is rising for PDMPs, and Europe faces a threat of supply shortages. Industry and patient groups are clear that using UK plasma would bring significant immediate benefits to patients and to the resilience of the European supply chain. From this scientific review, we conclude that UK plasma is safe for fractionation and urge blood regulators and operators to take account of this safety profile when considering fractionation of UK plasma, and to revise their guidelines on the deferral of donors who have lived in, or received a transfusion in, the United Kingdom., (© 2023 International Society of Blood Transfusion.)

Background: Phase 1 clinical trials represent a critical phase of drug development because new candidate therapeutic agents are tested for the first time on humans. Therefore, international guidelines and local laws have been released to mitigate and control possible risks for human health in agreement with the declaration of Helsinki and the international Good Clinical Practice principles. Despite numerous scientific works characterizing the registered clinical trials on ClinicalTrials.gov, the main features and trends of registered phase 1 clinical trials in Europe have not been investigated. This study is aimed at assessing the features and the temporal trend of distribution of phase 1 clinical studies, carried out in the five largest European countries over a ten-year period (2012-2021), and to evaluate the impact of the Italian regulatory framework on the activation of such studies., Methods: The main data and characteristics of phase 1 clinical studies registered on the ClinicalTrials.gov database for France, Germany, Italy, Spain and the United Kingdom have been investigated and subsequently compared. The above-mentioned countries were selected based on similarities in terms of demographic and Gross Domestic Product (GDP) data available on official government websites. (3) Results: A total number of 6878 phase 1 clinical trials were registered for the five selected countries in the ClinicalTrials.gov database during the ten years analyzed; the studies were predominantly randomized (39.33%) and for-profit (76.64%). The most represented area of investigations was oncology (52.15%), followed by hematology (24.99%) and immunology (12.04%). The variability observed between the analyzed countries showed that the UK, Germany and France presented the highest reduction in the number of phase 1 clinical trials, while for Spain and Italy, a stable/increased trend was observed, although with a lower number of trials registered on the ClinicalTrials.gov database. (4) Conclusions: Italy displayed the lowest number of registered phase 1 clinical trials, even though it showed a stable trend over the years. In this regard, the Italian regulatory framework must urgently be adapted to that of other European countries (Spain has been the first country to implement the new Regulation (EU) No 536/2014) and streamline the process of clinical trial application to increase the attractiveness of the country. Moreover, nonprofit phase 1 clinical trials (which represent 19.81% of the total number of phase 1 clinical trials registered in Italy vs. 80.19% of profit phase 1 clinical studies) should be promoted and supported by the institutions, even from a financial point of view, to allow independent researchers to develop new therapeutic drugs.

Background: Developed countries have a high prevalence of vitamin D deficiency. In previous studies, 25(OH)D was predominantly measured by immunoassays. The present study assessed serum 25(OH)D in a very large Southern European outpatient cohort by liquid chromatography tandem mass spectrometry (LC-MS/MS)., Materials and Methods: 74,235 serum 25(OH)D results generated under routine conditions between 2015 and 2016 were extracted from the laboratory information system of the Department of Clinical Pathology at Bolzano Hospital (Italy). In 3801 cases, parathyroid hormone (PTH) was requested in parallel. Serum 25(OH)D was measured by a NIST-972 aligned commercial LC-MS/MS method. The distribution of serum 25(OH)D concentrations in males and females of different age groups, the prevalence of 25(OH)D 2 and seasonal variability were studied., Results: The average 25(OH)D concentration in the entire cohort was 68.6 nmol/L (7.5-1880 nmol/L). Females had a 7 nmol/L higher average 25(OH)D concentration than males, which increased significantly with age. 37.9 and 28.3% of males and females, respectively, had a deficient 25(OH)D concentration of < 50 nmol/L. 620 samples (0.84%) had measureable amounts of 25(OH)D 2 . In samples with a normal PTH, 25(OH)D was 11 nmol/L higher than in the entire cohort. Seasonal variation ranged between 20 and 30% and was most pronounced in young individuals. 25(OH)D 2 remained constant throughout the year., Conclusion: Average serum 25(OH)D in South Tyrol is higher than in other parts of Europe. 25(OH)D and PTH show a continuous inverse relationship. Seasonal variation of serum 25(OH)D is an important aspect in young and middle-aged adults, but becomes less relevant in elderly subjects. 25(OH)D 2 is of minor practical importance in South Tyrol.

Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio-maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future., Aim: Within this narrative review, we discuss possible future biomaterials for bone replacement., Scientific Rationale for Study: Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce., Practical Implications: In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG., Results: We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision-making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations., Conclusions: We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To update the 2012 European Society of Musculoskeletal Radiology (ESSR) clinical consensus guidelines for musculoskeletal ultrasound referral in Europe., Methods: Twenty-one musculoskeletal imaging experts from the ESSR participated in a consensus study based on a Delphic process. Two independent (non-voting) authors facilitated the procedure and resolved doubtful issues. Updated musculoskeletal ultrasound literature up to July 2017 was scored for shoulder, elbow, wrist/hand, hip, knee, and ankle/foot. Scoring of ultrasound elastography was included. The strength of the recommendation and level of evidence was scored by consensus greater than 67% or considered uncertain when the consensus was consensus less than 67%., Results: A total of 123 new papers were reviewed. No evidence change was found regarding the shoulder. There were no new relevant articles for the shoulder, 10 new articles for the elbow, 28 for the hand/wrist, 3 for the hip, 7 for the knee, and 4 for the ankle/foot. Four new evidence levels of A were determined, one for the hip (gluteal tendons tears), one for the knee (meniscal cysts), one for the ankle (ankle joint instability), and one for the foot (plantar plate tear). There was no level A evidence for elastography, although for Achilles tendinopathy and lateral epicondylitis evidence level was B with grade 3 indication., Conclusions: Four new areas of level A evidence were included in the guidelines. Elastography did not reach level A evidence. Whilst ultrasound is of increasing importance in musculoskeletal medical practice, the evidence for elastography remains moderate., Key Points: • Evidence and expert consensus shows an increase of musculoskeletal ultrasound indications. • Four new A evidence levels were found for the hip, knee, ankle, and foot. • There was no level A evidence for elastography.

Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics. While commercially available tests are being developed, potential surrogate antibiotics may be used as marker of susceptibility. Using tedizolid as an example of a new antibiotic, this special report makes recommendations to optimize routine susceptibility reporting.

The link between diet and health has been recognized since the Grecian period; as Hippocrates said, "Let food be your medicine and medicine be your food". Although the primary goals of diet are meeting nutritional requirements and providing energy, there is increasing awareness that a correct and balanced diet may prevent the insurgence of diet-related pathologies and/or improve well-being and life expectancy, also reflecting on the ageing process. Research on the interaction among nutrients, gut microbiota and host metabolism is presently unravelling the molecular mechanisms underlying the positive and negative effects of traditional diets on health and ageing, providing useful information for the design of innovative foods targeting specific needs and segments of the population. The food supply chain plays a key role in ensuring quality and safety through both comprehensive quality management and inspection systems and a focused innovation process mainly devoted to the creation of functional foods. However, innovation and scientific development pose a problem of information asymmetry towards final consumers; thus, regulatory aspects and private and public communication strategies must be efficiently developed.

The viral safety of IVIg is defined by transposition of European Directives. Directive 89/381/CEE defines plasma-derived medicinal products (pd-MP) which should be registred through a Marketing Authorization (75/318/CEE) and requires specific criteria for donation acceptability and fractionation processing. Recommendations and Notes for Guidance are prepared by the "Biotechnology Working Party" (BWP), Committee for Proprietary Medicinal Products (CPMP) ad hoc group. "Note for Guidance on Virus Validation Studies: CPMP/BWP/268/95" defines, for conventional viruses, the validation study as regards viral elimination /inactivation steps (relevant virus, scale reduction system and statistical interpretation of the results). "Note for Guidance on 'blood products'- CPMP/BWP/269/95" defines the key issues of viral safety: starting material, viral elimination /inactivation steps within the fractionation processing and in process controls. Pd-MP used as excipients are also covered. BWP/CPMP recommends that exclusion criteria only be considered for sporadic, familial or iatrogenic Creutzfeldt-Jakob disease (CJD), while withdrawal should be undertaken, according to the precaution principle, when a donor is suffering from nv-CJD (February 1998). Also, screening tests currently under development for transmissible spongiform encephalopathies are encouraged to be introduced for fractionation products (January 1999). Some donor exclusion criteria for conventional viruses and prions are specific to France. In conclusion, measures taken to ensure pd-MP viral safety are constantly changing. Its evaluation can only be done when considering numerous parameters within a global context.

Economic evaluations of pharmaceuticals are increasingly being conducted in conjunction with randomized phase III clinical trials to meet the demand for pharmacoeconomic data when new products are launched. While the need for such data is often global, the trials in which relevant information may be collected are often conducted in only one or a limited number of countries. A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others. We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease (rhDNase), which is used to improve pulmonary function in patients with cystic fibrosis (CF). The objective of these evaluations was to estimate the potential impact of rhDNase therapy in France, Germany, Italy, and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections (RTIs) in patients with CF. Analyses of economic impact were undertaken both with and without adjustment for differences in practice patterns between the United States and the countries of interest. Our findings suggest that rhDNase therapy may reduce the cost of RTI-related care by between US$600 and US$1,100 over a 24-week period; the cost of rhDNase is not included in these figures, as a price was unavailable when our analyses were undertaken. Despite methodologic challenges, economic evaluations that meet the information needs of decision makers in diverse countries can nonetheless be undertaken in conjunction with phase III clinical trials.

During the Dark ages, Greco-Roman science survived in the eastern Roman Empire and the most important advances in pharmacology and pharmacy were made in Byzantium. As the Arab empires spread in the 7th and 8th centuries, they incorporated earlier learning, and the most important contribution of Arabic medical writers was probably the introduction of formularies to aid in the preparation of medicines. In turn, the later spread of Arabic knowledge to the West introduced little-known plants and fostered an interest in collecting and cultivating them, and also introduced the palatable dose forms preferred by the Arabic doctors. In the West, however, the Christian Church taught a doctrine of unquestioning faith, and despite the centers of learning, e.g. at Salerno, most ordinary people depended on the healing power of faith, religious relics and traditional folk medicine. Hydrology was also well developed in the Middle Ages. The formularia that survive describe many indigenous plants, but with few illustrations. Their gathering and preparation is generally guided by magic ceremonies and ritual, and plants often took their properties from their habitat, e.g. the wayside plantain was thought good for tired or wounded feet. Concepts of therapeutic plants were also influenced by alchemy and were linked to related metals and planets.

The habitual use of drugs acting on the human mental faculties is very ancient. An overview on the history of cocaine, from the pre-Colombian populations of South-America to our days, is reported.

This paper considers the descriptive capacity of Italian census data on spatial mobility. A systematic comparison is carried out between the Italian census and traditional sources--particularly the population register. The discussion concerns the items collected and published as well as the measurements obtained, their meaning, and their comparability. Many examples are presented, especially on migration flows during the 1976-1981 period, as recorded by the 1981 Italian population census, applied to the whole country as well as the regions, with particular reference to the Veneto region.