Structural Health Monitoring Based on Acoustic Emissions: Validation on a Prestressed Concrete Bridge Tested to Failure.

The increasing number of bridges approaching their design life has prompted researchers and operators to develop innovative structural health monitoring (SHM) techniques. An acoustic emissions (AE) method is a passive SHM approach based on the detection of elastic waves in structural components generated by damages, such as the initiation and propagation of cracks in concrete and the failure of steel wires. In this paper, we discuss the effectiveness of AE techniques by analyzing records acquired during a load test on a full-size prestressed concrete bridge span. The bridge is a 1968 structure currently decommissioned but perfectly representative, by type, age, and deterioration state of similar bridges in operation on the Italian highway network. It underwent a sequence of loading and unloading cycles with a progressively increasing load up to failure. We analyzed the AE signals recorded during the load test and examined how far their features (number of hits, amplitude, signal strength, and peak frequency) allow us to detect, quantify, and classify damages. We conclude that AE can be successfully used in permanent monitoring to provide information on the cracking state and the maximum load withstood. They can also be used as a non-destructive technique to recognize whether a structural member is cracked. Finally, we noticed that AE allow classifying different types of damage, although further experiments are needed to establish and validate a robust classification procedure.

On the Policy of the Italian Government in the Discovery, Development, and Access to Medicines.

This commentary outlines how discovery, development, and access to medicines are regulated and promoted in Italy by the government through the Ministry of University and Research, the Ministry of Health, and the Italian Medicines Agency. We describe and comment on the existing research programs stimulating preclinical, translational, and clinical research and how access to medicines and their pricing is regulated by Italy's National Health Service both at the national and regional levels. Finally, we describe the current scenario of industrial research and medicines manufacturing. The resulting picture shows a country in which high-level competitive research on medicines is promoted alongside an excellent national health system working toward fairness of access to health care services for all citizens and fiscal solidarity as a fundamental form of system financing. Critical challenges still exist, including the relative scarcity of public funding for research and the non-uniform access to the benefits of the National Health Service across Italian regions.

Can causality assessment fulfill the new European definition of adverse drug reaction? A review of methods used in spontaneous reporting.

Causality assessment is a fundamental biomedical technique for the signal detection performed by Pharmacovigilance centers in a Spontaneous reporting system. Moreover, it is a crucial and important practice for detecting preventable adverse drug reactions. Among different methods for causality assessment, algorithms (such as the Naranjo, or Begaud Methods) seem for their operational procedure and easier applicability one of the most commonly used methods. With the upcoming of the new European Pharmacovigilance legislation including in the definition of the adverse event also effects resulting from abuse, misuse and medication error, all well-known preventable causes of ADRs, there was an emerging need to evaluate whether algorithms could fulfill this new definition. In this review, twenty-two algorithmic methods were identified and none of them seemed to fulfill perfectly the new criteria of adverse event although some of them come close. In fact, several issues were arisen in applying causality assessment algorithms to these new definitions as for example the impossibility to answer the rechallenge question in case of medication error or AEFI (Adverse Event Following Immunization). Moreover, the exact conditions at which events occurred, as for example dosage or mode of administration should be considered to better assess causality in conditions of abuse/overdose, or misuse as well as in conditions of lack of expected efficacy reports for biotechnological drugs and adverse event occurring after mixing of vaccines. Therefore, this review highlights the need of updating algorithmic methods to allow a perfect applicability in all possible clinical scenarios accordingly or not with the terms of marketing authorization.

Campania Region (Italy) spontaneous reporting system and preventability assessment through a case-by-case approach: a pilot study on psychotropic drugs.

OBJECTIVE: We conducted the first pilot Italian study to assess the preventability of adverse drug reactions involving psychotropic drugs reported through spontaneous reporting system from 01/07/2012 to 31/12/2014 in Campania Region. METHODS: Preventability was assessed, case-by-case, using an adapted version of the P-method. The evaluation was performed only for those reports that had, as suspected drug, antipsychotics, mood stabilizers, antidepressants, anxiolytic and/or sedative-hypnotic. RESULTS: Eighty-one cases (19.2%) out of 421 reported during the study period were preventable. In seventy-seven (95.1%) out of 81 preventable cases, the underlying mechanism of the adverse drug reactions was dose-related, in four (4.9%) preventable cases the underlying mechanism of the adverse drug reactions was respectively susceptibility- (1; 1.2%), unknown- (1; 1.2%) and time-related (2; 2.5%). In the 81 preventable cases, 97 critical criteria were detected of which 29/97 (29.9%) related to healthcare professionals' practices, 0/97 (0.0%) to drug quality and 68/97 (70.1%) to patient behaviour. CONCLUSIONS: We proved that it was possible to apply and adapt the P-Method to assess the preventability of the adverse drug reactions involving psychotropic drugs, analysing individual case safety report sent through Campania Region spontaneous reporting system. Information acquired will be used to organize educational activities for both physicians and patients to promote a more appropriate drug use.

Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

BACKGROUND: According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. OBJECTIVES AND METHODS: The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-ß-cyclodextrin (HPßCD) and progesterone/HPßCD associations. RESULTS: The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPßCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPßCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the new formulation of progesterone was shown to be safe and not inferior to other products already on the market, with the exception of progesterone administered vaginally. CONCLUSIONS: As shown by the results of clinical studies presented in this review, the newly approved medicines containing cyclodextrins have been found to be as effective and as well-tolerated as other medicinal products that do not contain cyclodextrins. Moreover, the newly approved lower dose of diclofenac associated with cyclodextrins is consistent with the European Medicines Agency recommendations reported in the revision of the Assessment Report for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Cardiovascular Risk. Finally, the use of cyclodextrins led to significant increases in solubility and bioavailability of drugs, such as diclofenac and progesterone, and improvement in the efficacy and safety of these drugs.