[About direct and on behalf delivery of drugs.] / A proposito della distribuzione dei medicinali diretta e per conto.

Italian Medicines Agency (AIFA) intervenes in the debate that started from the parliamentary inquiry of the Chamber of Deputies at the XII Commission on the issue of the convenience, or not, of the transition from direct distribution (DD) to distribution on behalf (DPC) of local health companies, providing further data and additional information from the AIFA Medicines Observatory (OsMed). The availability of data and processing and the introduction of stringent criteria in the possible application of this distribution transfer, reduces the impact in terms of higher costs, estimated at 320 million euro/year. However, the contribution does not take into account that, on the basis of a regulatory automatism inserted in the Agreements between 7 Regions and the Unions of pharmacies, it is foreseeable a further transfer of medicines from DPC to retail distribution, today diversified on the basis of the different public price values of medicines (range 10-50 euro): this could result in an additional cost burden for the National Health Service (NHS) estimated at over 160 million due to the effect of the cessation of the cost reduction resulting from the tender savings and the emergence of the remuneration of the entire distribution chain. The final impact could therefore be very high in terms of additional expenditure for NHS.

Signalling and responding to zoonotic threats using a One Health approach: a decade of the Zoonoses Structure in the Netherlands, 2011 to 2021.

In the Netherlands, the avian influenza outbreak in poultry in 2003 and the Q fever outbreak in dairy goats between 2007 and 2010 had severe consequences for public health. These outbreaks led to the establishment of an integrated human-veterinary risk analysis system for zoonoses, the Zoonoses Structure. The aim of the Zoonoses Structure is to signal, assess and control emerging zoonoses that may pose a risk to animal and/or human health in an integrated One Health approach. The Signalling Forum Zoonoses (SO-Z), the first step of the Zoonoses Structure, is a multidisciplinary committee composed of experts from the medical, veterinary, entomology and wildlife domains. The SO-Z shares relevant signals with professionals and has monthly meetings. Over the past 10 years (June 2011 to December 2021), 390 different signals of various zoonotic pathogens in animal reservoirs and humans have been assessed. Here, we describe the Zoonoses Structure with examples from signals and responses for four zoonotic events in the Netherlands (tularaemia, Brucella canis, West Nile virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)). This may serve as an example for other countries on how to collaborate in a One Health approach to signal and control emerging zoonoses.

Burden of uterine fibroids in Italy: epidemiology, treatment outcomes, and consumption of health care resources in more than 5,000 women.

BACKGROUND AND PURPOSE: Epidemiological studies on uterine fibroids (UFs) are mostly based on surveys or analyses of small samples of patients. In 50% of women, the quality of life is worsened by disease-related symptoms; furthermore, treatments imply a remarkable health care cost. The aim of this observational study was to analyze a large sample of Italian patients with UFs and to assess the epidemiology, the appropriateness of treatments, and the consumption of disease-related resources. METHODS: Data were collected through a data-linkage technique from five administrative databases. Women aged between 18 and 55 years and resident in three local health authorities (north-central-south Italy) were selected over the period from 1st January 2009 to 31st December 2015. The inclusion criteria were a surgical procedure with diagnosis of UFs or a pharmacological treatment with gonadotropin-releasing hormone (GnRH) analogs or ulipristal acetate. Besides the overall descriptive analysis, two comparisons were evaluated: surgery versus no surgery and treatment with GnRH analogs versus ulipristal acetate. RESULTS: A total of 5,665 women with UFs were selected from an overall population of 2,400,000 people. In the north, 73.6% of patients underwent surgery, as opposed to only 16.7% in the south; 70% of surgeries were hysterectomies. The average cost per patient was €3,249 (duration of follow-up = up to 7 years). The southern district had the highest number of drug prescriptions; in particular, 49% of patients took >10 packages of GnRH analogs. CONCLUSION: This study is the first on this topic conducted in Italy using a large sample size. The analysis of resource consumption revealed a high heterogeneity in the choice of drug treatments by gynecologists (especially in the south); in the north, marked variations were seen in the rates of surgery. The long-term use of GnRH was inappropriate.

Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014.

In the Netherlands, 97 human leptospirosis cases were notified in 2014. This represents a 4.6-fold increase in autochthonous cases (n = 60) compared with the annual average between 2010 and 2013. Most cases had symptom onset between June and November. This marked increase in humans coincided with an increase of leptospirosis in dogs. In 2014, 13 dogs with leptospirosis were reported, compared with two to six dogs annually from 2010 to 2013. The majority of the autochthonous cases (n = 20) were linked to recreational exposure, e.g. swimming or fishing, followed by occupational exposure (n = 15). About sixty per cent (n = 37) of the autochthonous cases were most likely attributable to surface water contact, and 13 cases to direct contact with animals, mainly rats. A possible explanation for this increase is the preceding mild winter of 2013-2014 followed by the warmest year in three centuries, possibly enabling rodents and Leptospira spp. to survive better. A slight increase in imported leptospirosis was also observed in Dutch tourists (n = 33) most of whom acquired their infection in Thailand (n = 18). More awareness and early recognition of this mainly rodent-borne zoonosis by medical and veterinary specialists is warranted.

The safety of bevacizumab and ranibizumab in clinical studies.

In comparing the safety of ranibizumab versus bevacizumab in age-related macular degeneration, the meta-analyses published thus far have given conflicting results, particularly about the risk of venous thrombotic events and ocular inflammation. From the comparison of the design and the findings of these meta-analysis, we tried to identify the potential explanations to account for these discrepancies. We separately evaluated the incidence of ocular inflammation with the two agents between randomized studies and non-randomized studies. While no increase in risk was found in randomized studies, non-randomized studies showed an increase in risk for bevacizumab versus ranibizumab. One interpretation of these findings is that bevacizumab itself does not represent any increase in risk of ocular inflammation and/or cardiovascular events under the rigorous conditions of a randomized study, but this agent can be at the origin of an increase in risk when administered in the "real world"; this setting could in fact leave space for less strictly controlled preparation of aliquots for intravitreal injection.

Biological drugs for the treatment of rheumatoid arthritis by the subcutaneous route: interpreting efficacy data to assess statistical equivalence.

BACKGROUND: No equivalence analysis has yet been conducted on the effectiveness of biologics in rheumatoid arthritis. Equivalence testing has a specific scientific interest, but can also be useful for deciding whether acquisition tenders are feasible for the pharmacological agents being compared. METHODS: Our search covered the literature up to August 2014. Our methodology was a combination of standard pairwise meta-analysis, Bayesian network meta-analysis and equivalence testing. The agents examined for their potential equivalence were etanercept, adalimumab, golimumab, certolizumab, and tocilizumab, each in combination with methotrexate (MTX). The reference treatment was MTX monotherapy. The endpoint was ACR50 achievement at 12 months. Odds ratio was the outcome measure. The equivalence margins were established by analyzing the statistical power data of the trials. RESULTS: Our search identified seven randomized controlled trials (2846 patients). No study was retrieved for tocilizumab, and so only four biologics were evaluable. The equivalence range was set at odds ratio from 0.56 to 1.78. There were 10 head-to-head comparisons (4 direct, 6 indirect). Bayesian network meta-analysis estimated the odds ratio (with 90% credible intervals) for each of these comparisons. Between-trial heterogeneity was marked. According to our results, all credible intervals of the 10 comparisons were wide and none of them satisfied the equivalence criterion. A superiority finding was confirmed for the treatment with MTX plus adalimumab or certolizumab in comparison with MTX monotherapy, but not for the other two biologics. CONCLUSION: Our results indicate that these four biologics improved the rates of ACR50 achievement, but there was an evident between-study heterogeneity. The head-to-head indirect comparisons between individual biologics showed no significant difference, but failed to demonstrate the proof of no difference (i.e. equivalence). This body of evidence presently precludes any option of undertaking competitive tenderings for the procurement of these agents.

Intravenous proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: determining statistical equivalence according to evidence-based methods.

BACKGROUND: Although intravenous proton pump inhibitors (PPIs) are considered at least as effective as H2-receptors antagonists for stress ulcer prophylaxis (SUP) in critically ill patients, there is no data on whether there is also the proof of no difference among these agents. METHODS: The clinical material was the same as that reported in previous meta-analyses and included all trials comparing intravenous PPIs vs. H2-receptor antagonists for SUP in critically ill patients. Our methodology was a combination of meta-analysis and equivalence testing based on confidence intervals (CIs). The end-point was the rate of overt bleeding. All PPIs evaluated in the included trials were separately studied. The equivalence margins were derived from power calculation data of the original trials. RESULTS: Our analysis involved 8 randomized trials for 851 patients. Two comparisons were made (pantoprazole vs. H2-receptor antagonists and omeprazole vs. H2-receptor antagonists). The following RDs were estimated: pantoprazole, RD = -1.2%, 95% CI: -3.5% to +1.2%; omeprazole, RD = -3.0%, 95% CI: -7.2% to +1.3%. The 95% CIs confidence intervals for RDs remained within the ± 6% margin. These results indicate that intravenous pantoprazole and intravenous omeprazole are equivalent, Conclusion: These two PPIs, when administered by intravenous route, are equivalent according to reasonable equivalence margins. This conclusion can be the basis to develop local acquisition tenders on these drugs. One advantage of this approach is that the feasibility of administrative decisions can directly be tested on clinical grounds and on the basis of standard evidence-based methods.

Biological drugs for the treatment of moderate-to-severe psoriasis by subcutaneous route: determining statistical equivalence according to evidence-based methods.

BACKGROUND: Although several evidence-based analyses have found that in patients with moderate-to-severe psoriasis, biological agents for subcutaneous use show no difference in efficacy (no proof of difference), there is limited evidence on whether or not there is also proof of no difference. METHODS: The clinical material was the same as that reported in previous meta-analyses. Our methodology was a combination of meta-analysis and equivalence testing. The endpoint was the rate of Psoriasis Area and Severity Index (PASI) 75 achievement. The agents examined for equivalence testing included etanercept, high-dose etanercept, adalimumab, ustekinumab, and high-dose ustekinumab. The equivalence margin [±18 % as risk difference (RD)] was derived from statistical power information from the original trials; a more conservative margin at ±10 % was also tested. RESULTS: Our analysis involved 16 randomized trials including 8,257 patients. Ten head-to-head indirect comparisons were made and the respective values of RD were estimated. The 95 % confidence intervals for RDs remained within the margins of ±18 and ±10 % in six and two cases, respectively. A post hoc margin of about ±25 % was satisfied in all cases. All analyses assumed α = 2.5 %. CONCLUSION: Our study indicates that some of these five biological treatments can be equivalent, but results are strongly influenced by the margins adopted. Our findings can be helpful to develop local acquisition tenders on these drugs.

Risk analysis-based food safety policy: scientific factors versus socio-cultural factors.

The purpose of this article is to illustrate the importance of socio-cultural factors in risk management and the need to incorporate these factors in a standard, internationally recognized (WTO) framework. This was achieved by analysing the relevance of these factors in three cases. It can be concluded that the pre-eminent role of science in food-related regulatory decisions is debatable. At a risk management level, other factors, such as cultural, social, or economic issues, are often more important than scientific advice in determining policy. There is a need for transparency at an international level as trade barriers are gradually being removed and these other factors are becoming more apparent. Therefore it is important that all the factors implicated in the food safety policy-making process are recognized in a standard framework.

New approaches for education and training in veterinary public health: the SAPUVET projects.

Continued contact between humans and animals, in combination with the ever-increasing movement of human and animal populations that is one effect of globalization, contributes to the spread of diseases, often with detrimental effects on public health. This has led professionals involved in both animal health and public health to recognize veterinary public health (VPH) as a key area for their activities to address the human-animal interface. Veterinarians, a profession with major involvement in this field, are in need of specific knowledge and skills to prevent and control public-health problems. As a result, VPH must be directly integrated into veterinary educational programs. At present, only few veterinary schools have specific VPH programs; in most institutions, VPH does not feature as a specific subject in either undergraduate or post-graduate curricula. SAPUVET and SAPUVETNET II are network projects supported by the ALFA program of the European Union (EU). Their main objectives are to reach a common understanding between European and Latin American universities in the definition of the areas in which VPH is important in their respective countries, and to design a harmonized training program for veterinarians in VPH, by making use of new technological applications and innovative teaching methodologies. The elaboration of educational material in combination with case studies presenting real-life problems provides a basis to apply the knowledge acquired on VPH. It is envisaged that the material and modules developed during the two projects will be integrated into the veterinary curricula of the participating universities, as well as in other partner organizations.

Experiences and difficulties encountered during a course on veterinary public health with students of different nationalities.

Veterinary public health (VPH) issues have received increased attention over the last few years as a result of the rising threat of emerging zoonoses (i.e., those due to globalized trade in animal and animal products and to changes in livestock production systems and the environment). The international dimension of VPH is gradually becoming recognized, and there is a growing need for veterinarians with experience in this field. In order to familiarize (future) veterinarians with the international dimension of VPH, the Department of Public Health and Food Safety of the Faculty of Veterinary Medicine, Utrecht University, has been organizing a course in Veterinary Public Health and Animal Production for over the last 10 years. This course has been intended for Dutch as well as foreign final-year veterinary students and recent veterinary graduates. By bringing together participants from different countries, the course reinforces the international dimension of the issues addressed through the exchange of experiences by the participants themselves. The present article provides information about this course on Veterinary Public Health (VPH): it discusses logistics, didactical approaches, the course program, and the use of information and communication technology (ICT). Special attention is given to the intercultural aspects of higher education, all of which play an important role in the efficient exchange of knowledge between lecturers and students. International courses are an important tool to enable participants to interact in a multicultural environment and address issues that demand international cooperation and a global public health focus.