European Health Authorities Research Articles

Prevalence and burden of dengue infection in Europe: A systematic review and meta-analysis.

Imported dengue cases are thought to be important source for transmission of autochthonous dengue in Europe. We aimed to investigate the prevalence of dengue in Europe, its severity, and factors associated with it. Out of 5287 reports resulting from the search of nine electronic search engines, we included 174 reports. Meta-analysis was performed by pooling the event rate and 95% confidence interval (CI). Subgroup meta-analyses were performed to test the effect of the covariates. Among 20 284 reported cases, 130 autochthonous dengue cases were reported in eight countries with the highest number of cases reported in Israel (n = 41). The highest number of imported dengue cases was in Germany (n = 6638) then France (n = 6610). Most cases were imported from Southeast Asia (n = 2533) especially Thailand. Dengue infection cases increased with time, with 4157 cases reported in 2010. Second dengue infection and dengue serotype 2 were positively associated with dengue severity. The proportion of autochthonous dengue infection increased with time to reach 14.8% (95% CI, 7.6-26.9) in 2015. The pooled proportion of severe dengue was 6.18% (95% CI, 2.7-13.3). The United Kingdom and France had the highest rate of severe dengue (25%; 95% CI, 6.3-62.3, and 21.4%; 95% CI, 24.5-18.7, respectively). This change may be due to the surveillance efforts instead of true biological phenomenon; thus, the lack of surveillance is an obvious limitation. In conclusion, imported and autochthonous dengue has been increasing in Europe. Severe dengue began to increase recently in Europe. European health authorities should pay more attention for the diagnosis and control of dengue infection among returning travelers, especially the travelers with fever of unknown origin.

Current Rabies Vaccines Do Not Confer Protective Immunity against Divergent Lyssaviruses Circulating in Europe.

The use of the rabies vaccine for post-exposure prophylaxis started as early as 1885, revealing a safe and efficient tool to prevent human rabies cases. Preventive vaccination is the basis for the control of canine-mediated rabies, which has already been eliminated from extensive parts of the world, including Europe. Plans to eliminate canine-mediated human rabies by 2030 have been agreed upon by international organisations. However, rabies vaccines are not efficacious against some divergent lyssaviruses. The presence in European indigenous bats of recently described lyssaviruses, which are not neutralised by antibody responses to existing vaccines, as well as the declaration of an imported case of an African lyssavirus, which also escapes vaccine-derived protection, leaves the European health authorities unable to provide efficacious protective vaccines to some potential situations of human exposure. All these circumstances highlight the need for a universal pan-lyssavirus rabies vaccine, able to prevent human rabies in all circumstances.

Availability of Effective Evidence-Based Symptomatic Treatments for Cluster Headache in the EU Countries-A Survey of the European Headache Alliance and European Headache Federation.

To assess the reimbursement options and accessibility of three effective medicines for cluster headache (CH) (subcutaneous sumatriptan, oxygen, and zolmitriptan spray) across the European Union (EU). A brief survey investigating the availability of symptomatic treatments for CH was sent by email in January 2017 to at least one headache specialist for every single country in the EU. The questionnaire was completed by 26 headache specialists (93% of the EU countries, representing 99.75% of the European population) and by 10 CH patients representative of patient organizations. Oxygen was reimbursable for 63% of the CH population. Oxygen device was reimbursable for 50% of the CH EU population. Subcutaneous sumatriptan was reimbursable for 66% and was accessible without restrictions for 45% of the CH EU population. Zolmitriptan spray was reimbursable for 23.7% and accessible without restrictions for 30.9% of the CH EU population. Only 47% of the EU population had unrestricted access to effective CH treatments, with unacceptable inequalities between eastern countries and the rest of Europe. Headache societies and patient associations should pressure European and national health authorities to improve the availability of effective symptomatic treatments for CH.

Pricing of oral generic cancer medicines in 25 European countries; findings and implications

Introduction: There are appreciable concerns among European health authorities with growing expenditure on cancer medicines and issues of sustainability. The enhanced use of low cost generics could help. Aims: Consequently, there is a need to comprehensively document current and future arrangements regarding the pricing of generic cancer medicines across Europe, and whether these are indication specific, as well as how this translates into actual prices to provide future direction. Methodology: Mixed method approach with qualitative research among senior health authority personnel and their advisers. Quantitative research via health authority databases to ascertain current prices for oral cancer medicines that had lost their patent and the influence of population size and economics on prices. Results: 25 European countries participated. Currently we see (a) variable approaches to the pricing of generic cancer medicines, which will continue; (b) no concerns with substitution for oral generic cancer medicines; (c) substantial price reductions versus originators for generic capecitabine (up to -93.1%), generic imatinib (up to -97.8%) and generic temozolomide (up to -80.7%). Prices for oncology medicines are not indication specific, and are not affected by population size although influenced by pricing approaches. There have also been price increases for some non-patented cancer medicines following manufacturer changes although now stabilising. Conclusion: The considerable price reductions seen for some generics means health authorities should further encourage the use of generic oncology medicines when they become available to fund increased volumes and new valued cancer medicines. Countries are also starting to address price increases for generics following changes in the manufacturer

Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Coq6 Knockout Mice.

Although studies have identified >55 genes as causing steroid-resistant nephrotic syndrome (SRNS) and localized its pathogenesis to glomerular podocytes, the disease mechanisms of SRNS remain largely enigmatic. We recently reported that individuals with mutations in COQ6, a coenzyme Q (also called CoQ10, CoQ, or ubiquinone) biosynthesis pathway enzyme, develop SRNS with sensorineural deafness, and demonstrated the beneficial effect of CoQ for maintenace of kidney function. To study COQ6 function in podocytes, we generated a podocyte-specific Coq6 knockout mouse (Coq6podKO ) model and a transient siRNA-based COQ6 knockdown in a human podocyte cell line. Mice were monitored for development of proteinuria and assessed for development of glomerular sclerosis. Using a podocyte migration assay, we compared motility in COQ6 knockdown podocytes and control podocytes. We also randomly assigned 5-month-old Coq6podKO mice and controls to receive no treatment or 2,4-dihydroxybenzoic acid (2,4-diHB), an analog of a CoQ precursor molecule that is classified as a food additive by health authorities in Europe and the United States. Abrogation of Coq6 in mouse podocytes caused FSGS and proteinuria (>46-fold increases in albuminuria). In vitro studies revealed an impaired podocyte migration rate in COQ6 knockdown human podocytes. Treating Coq6podKO mice or cells with 2,4-diHB prevented renal dysfunction and reversed podocyte migration rate impairment. Survival of Coq6podKO mice given 2,4diHB was comparable to that of control mice and significantly higher than that of untreated Coq6podKO mice, half of which died by 10 months of age. These findings reveal a potential novel treatment strategy for those cases of human nephrotic syndrome that are caused by a primary dysfunction in the CoQ10 biosynthesis pathway.

Etanercept biosimilar SB-4

ABSTRACTIntroduction: Biosimilars are highly similar molecules to other biological medicines that have already been authorized for use. Etanercept (ETN) was the first anti-tumor necrosis factor inhibitor (TNFi) approved by the Food and Drug Administration for the treatment of moderate to severe rheumatoid arthritis (RA) in November 1998 and in February 2000 by the European Medicines Agency. Twenty years later, the first ETN biosimilar has come of age.Areas covered: In this review we examined SB-4 as a biosimilar candidate to ETN, focusing on the available data. Current data indicate that SB-4 is a highly similar alternative to ETN in terms of safety, efficacy, tolerability, and immunogenicity. SB-4 has already been approved by health authorities in Europe, South Korea, Australia, and Canada, as a subcutaneous therapy option for the treatment of patients with RA but also for the full spectrum approved for its bio-originator ETN.Expert opinion: The current body of evidence suggests that all biologic activities have been demonstrated to be equivalent between SB-4 and the originator, including pharmacodynamic and pharmacokinetic activities. In some areas, and more specifically when it comes to immunogenicity, SB-4 showed lower incidents. Therefore, it is fully expected to have same efficacy and safety in all indications.

New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab.

The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naïve metastatic NSCLC with ≥50% of tumor cells expressing PDL1 and for metastatic NSCLC with ≥1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy. In 2017, it also authorized the first-line combination of pembrolizumab and carboplatin–pemetrexed chemotherapy without selection based on PDL1 expression, but European health authorities are still waiting for the results of a Phase III trial. In this review, the clinical results of published and ongoing studies evaluating pembrolizumab for advanced NSCLC are analyzed and the potential role of PDL1 as a factor predictive of overall responses addressed.

ABP 501 for the treatment of rheumatoid arthritis

ABSTRACTIntroduction: Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Tumour necrosis factor α (TNF) is a cytokine with diverse cellular effects, and a key regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a TNF inhibitor.Areas covered: In this review, we examined ABP 501, as a biosimilar candidate to adalimumab in the treatment of RA focusing on the available data. Current data indicate that ABP 501 is a highly similar alternative to adalimumab in terms of safety, efficacy, tolerability and immunogenicity. ABP 501 has already been approved by health authorities in Europe and the United States of America, as a subcutaneous (s.c.) therapy option for the treatment of patients with RA, but also for the full spectrum approved for its bio-originator adalimumab.Expert opinion: Current body of evidence suggests that all biologic activities have been demonstrated to be equivalent between ABP 501 and the originator, including binding rates and affinity to TNF, and also the effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC). Therefore, it is fully expected to have same efficacy and safety in all indications.

A QRM Discussion of Microbial Contamination of Non-sterile Drug Products, Using FDA and EMA Warning Letters Recorded between 2008 and 2016.

Microbial quality control of non-sterile drug products has been a concern to regulatory agencies and the pharmaceutical industry since the 1960s. Despite being an old challenge to companies, microbial contamination still affects a high number of manufacturers of non-sterile products. Consequences go well beyond the obvious direct costs related to batch rejections or product recalls, as human lives and a company's reputation are significantly impacted if such events occur. To better manage risk and establish effective mitigation strategies, it is necessary to understand the microbial hazards involved in non-sterile drug products manufacturing, be able to evaluate their potential impact on final product quality, and apply mitigation actions. Herein we discuss the most likely root causes involved in microbial contaminations referenced in warning letters issued by US health authorities and non-compliance reports issued by European health authorities over a period of several years. The quality risk management tools proposed were applied to the data gathered from those databases, and a generic risk ranking was provided based on a panel of non-sterile drug product manufacturers that was assembled and given the opportunity to perform the risk assessments. That panel identified gaps and defined potential mitigation actions, based on their own experience of potential risks expected for their processes. Major findings clearly indicate that the manufacturers affected by the warning letters should focus their attention on process improvements and microbial control strategies, especially those related to microbial analysis and raw material quality control. Additionally, the WLs considered frequently referred to failures in quality-related issues, which indicates that the quality commitment should be reinforced at most companies to avoid microbiological contaminations.LAY ABSTRACT: Microbial contamination of drug products affects the quality of non-sterile drug products produced by numerous manufacturers, representing a major risk to patients. It is necessary to understand the microbial hazards involved in the manufacturing process and evaluate their impact on final product quality so that effective prevention strategies can be implemented. A risk-based classification of most likely root causes for microbial contamination found in the warning letters issued by the US Food and Drug Administration and the European Medicines Agency is proposed. To validate the likely root causes extracted from the warning letters, a subject matter expert panel made of several manufacturers was formed and consulted. A quality risk management approach to assess microbiological contamination of non-sterile drug products is proposed for the identification of microbial hazards involved in the manufacturing process. To enable ranking of microbial contamination risks, quality risk management metrics related to criticality and overall risk were applied. The results showed that manufacturers of non-sterile drug products should improve their microbial control strategy, with special attention to quality controls of raw materials, primary containers, and closures. Besides that, they should invest in a more robust quality system and culture. As a start, manufacturers may consider investigating their specific microbiological risks, adressing their sites' own microbial ecology, type of manufacturing processes, and dosage form characteristics, as these may lead to increased contamination risks. Authorities should allow and enforce innovative, more comprehensive, and more effective approaches to in-process contamination monitoring and controls.

Complementary and Alternative Medicine Use and Initiatives in Europe

Complementary and Alternative Medicine Use and Initiatives in Europe

Benefits, benefits, once more benefits... with no risk? Stop overlooking the harms of medicines.

Consideration of drug benefits and harms is asymmetric. Approval of drugs is mainly based on efficacy, while the assessment of their safety is left to post-marketing commitments or spontaneous reporting. Benefits are overestimated as a result of pharmaceutical companies' advertisements, the paucity of independent information, and the scant understanding of the effectiveness of medicines in real life. Polypharmacy in older adults-even during the last period of their life-reflects the tendency to assign priority to efficacy and overlook harms, although nobody knows what happens when three or more drugs are given chronically. Medical journals and public research funding projects do not pay enough attention to drug toxicity. We call for a sense of purpose by all those involved in medicine to tackle this problem. European and national agencies and health authorities should promote and support independent information and experimental and clinical studies on drug toxicity. Information should rely not just on spontaneous reporting but also on active pharmacovigilance. The benefit-harm profile of drugs should be periodically reviewed in the light of toxic effects that come to light over the years. Potential interactions within polytherapies should be sought by re-assessing the pharmacokinetics and pharmacodynamics of their components.

How to include public health practice and practitioners in a European Network

There is a wide range of different Public Health (PH) activities and programs running in Europe. Besides the richness of national traditions, differences exist in numbers of programs, methods adopted, types of engaged professionals, available resources (including public investments), awareness to the problem and finally in health indicators among and within countries. Promoting networks of PH practices and practitioners strengthens the possibility to share knowledge across organizational, sectorial and geographic boundaries, promotes adaptation and local implementation, fosters innovation in the form of knowledge creation by developing more efficient new services and by sharing effective practices within and between organizations and sectors. Nevertheless, strengthening existing networks and promoting new ones requires coordinated efforts based on complex adaptive systems and network science rules, along with the engagement of local, national and European health authorities. Given these premises, networking promotion and development is a promising way to improve health and wealth to European citizens and communities.

Recreational drug use at a major music festival: trend analysis of anonymised pooled urine

Objective: The spread of new psychoactive substances (NPS) has expanded rapidly in the last decade. The complexity of the pharmacological effects of NPS challenges the traditional treatment guidelines, and information of the emergence of new arrivals is valuable. Our knowledge on the actual range of recreational drugs used and NPS available in Denmark is limited as identification is possible only when consumers become patients in the healthcare system or through drug seizures. We aimed to detect classical recreational drugs and NPS in the urine of music festival attendees and evaluate if the use of NPS could have been predicted by comparing study data with drug seizure data from the previous year published by European and Danish health authorities.Methods: In a cross-sectional study, 44 urine samples were collected from three urinals at Roskilde Festival 2016—the largest Danish music festival. Two urinals were placed at music stages with late-night concerts, and one urinal was placed at a camp site. Samples were prepared using enzymatic hydrolysis followed by cationic and anionic solid phase extraction, and analysed using ultra performance liquid chromatography-high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS). Data were processed using an in-house library of 467 target substances, including legal and illegal drugs and metabolites. Urine drug-screening immunoassays were also evaluated and results were compared to UPLC-HR-TOF-MS results.Results: In total, 77 drugs, including metabolites, were qualitatively identified in the 44 urine samples. The recreational drugs identified were amphetamine (n = 30), cocaine (n = 44), MDA (n = 40), MDMA (n = 44), THC-COOH (n = 19) and ketamine (n = 17). No NPS were identified. Sample testing using the urine drug-screening immunoassays showed presence of cocaine (n = 27), methamphetamine/MDMA (n = 4), THC (n = 7), “Spice” (n = 7) and methylphenidate (n = 1). These discrepancies might be caused by differences in cut-off values between the analytical methods, limited specificity or cross-reactivity of the urine drug-screening immunoassays compared to UPLC-HR-TOFMS results.Conclusion: Widespread uses of classical recreational drugs were identified in pooled urine samples. The prevalence of NPS was not as comprehensive as expected based on the European and Danish health authorities reports on illegal drugs. Urine drug-screening immunoassays results are advised to be confirmed by chromatographic bioanalysis.

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect

Objective: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance. Patients and Methods: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate. Results: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015). Conclusion: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

Clinical and economic issues complicating cost-effectiveness evaluation of orphan diseases

Abstract Cost-effectiveness evaluation of orphan medicinal products is confronted with a large confidence interval on the incremental cost-effectiveness ratios (ICERs), or extremely high ICERs and therefore rejection of products for uptake in the health insurance package (coverage) by health authorities in Europe. Examples from the United Kingdom (UK) and The Netherlands illustrated that straightforward application of the decision criteria might not always be possible, resulting in a large variety of coverage decisions that were neither transparent nor consistent with the criteria. This observation required more insight into what drives the high ICERs and what policies may support the appropriate use of orphan medicinal products. The most relevant clinical and economic issues that are perceived to complicate the cost-effectiveness evaluation of orphan medicinal products are discussed. Theoretically, two possible solutions are available: 1) circumvent or 2) keep the standard assessment criterion costeffectiveness. In analogy to the Europe Medicine Agency (EMA) registration approach of orphan medicinal products that are hampered by limitations in the clinical data at the time of registration, we suggest to stick to the use of standard uniform criteria, but that efforts should be directed at optimising the input to the cost-effectiveness evaluation. Subsequently potential policy approaches are developed.

Sirukumab: a promising therapy for rheumatoid arthritis

ABSTRACTIntroduction: Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Interleukin-6 (IL-6) wields pleiotropic biological effects that are crucially implicated in the activation of acute inflammatory response. Sirukumab is a monoclonal antibody with high affinity for IL-6.Areas covered: In this review, the authors examine sirukumab as a novel agent and its potential use in the treatment of RA focusing on the available data. Data from Phase I to Phase III indicate that sirukumab is generally safe and well tolerated by the patients with decreased inflammatory response. Sirukumab is currently awaiting approval by health authorities in Europe, the United States (U.S.) and Japan, as a subcutaneous (s.c.) therapy option for the treatment of adult patients with moderate to severely active RA.Expert opinion: Given the currently available literature on IL-6 and the IL-6 receptor antagonist tocilizumab, one could consider sirukumab as an attractive and promising alternative for RA therapy. Even if some Phase III trials are still ongoing and complete results are not fully available, sirukumab is clinically efficacious with a well-tolerated safety profile, and demonstrates non-inferiority when compared to TNFα inhibitors.

Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection.

The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

Transmissibility of Clostridium difficile Without Contact Isolation: Results From a Prospective Observational Study With 451 Patients.

Contact precautions are recommended by health authorities in Europe and the United States for patients with Clostridium difficile infection (CDI). Recently, the significance of nosocomial transmission has been challenged by screening on admission studies and whole-genome sequencing, providing evidence for an endogenous source of C. difficile. We discontinued contact precautions for patients with CDI, except for patients infected with hypervirulent ribotypes or with stool incontinence, to determine the rate of transmission. From January 2004 to December 2013, contacts of each index case with CDI were screened for toxigenic C. difficile by culturing rectal swabs. Transmission was defined as possible if toxigenic C. difficile was detected in contacts, as probable if the identical polymerase chain reaction ribotype was identified in index–contact pairs, and as confirmed if next-generation sequencing (NGS) revealed clonality of strains. Four hundred fifty-one contacts were exposed to 279 index patients nursed in 2-to 4-bed rooms. Toxigenic C. difficile was detected in 6.0% (27/451) after a median contact time of 5 days. Identical ribotypes were identified in 6 index–contact pairs, accounting for probable transmission in 1.3% (6/451). NGS was performed for 4 of 6 pairs with identical strains, and confirmed transmission in 2 contact patients. The rate of transmission of toxigenic, predominantly nonhypervirulent C. difficile, was low and no outbreaks were recorded over a 10-year period after discontinuing contact precautions for patients with CDI who were not severely incontinent and who used dedicated toilets. As contact precautions may lead to lower levels of care, their implementation needs to be balanced against the risk of nosocomial transmission.

Alkaloids in the valorization of European Lupinus spp. seeds crop

In this study, alkaloids from lupin varieties with commercial interest in Europe were identified and quantified. Additionally, the anti-inflammatory and antioxidant potential of some rich-alkaloid lupin extracts was assessed by 5-lipoxygenase (LOX) inhibition and nitric oxide radical (NO) scavenging assays, respectively. Relationships between extracts activity and those of pure standards were stablished.Nine alkaloids belonging to quinolizidine, indole and piperidine classes were identified by means of GC-IT/MS and quantified by GC-FID using a validated method. Lupanine was the most abundant alkaloid in white and narrow-leafed lupins (Lupinus albus L. and Lupinus angustifolius L., respectively) and sparteine in most yellow lupins (Lupinus luteus L.), but their proportions were cultivar-dependent. Gramine, smipine, angustifoline and lupanine derivatives were also identified. Five lupin varieties (Amiga, Estoril, Lumen, Dukat and Mister) were characterized as sweet (<0.5g alkaloids/kg, dry matter basis) and two of them respected the safety limit imposed by the European health authorities for human consumption (≤0.2g/kg, dry matter basis). Despite the weak effect on NO, a dose-dependent response towards LOX was found for all the studied extracts, which followed the order Taper>Estoril>Multitalia-PT>Dukat>Azuro>Multitalia-IT>Nacional.To our knowledge, the alkaloids composition of some of the varieties, as well as the study of the anti-inflammatory and antioxidant potential of rich-alkaloid lupin extracts are here reported for the first time. The results presented are a source of easily available data for producers, nutritionists and geneticists, and add biological knowledge on a major class of compounds in lupins.

The Syrian refugees crisis brings challenges to the health authorities in Europe: Hepatitis A Virus is a case in point

The Syrian refugees crisis brings challenges to the health authorities in Europe: Hepatitis A Virus is a case in point