Somatropin therapy in italian adults with growth hormone deficiency.

BACKGROUND: In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions. METHODS: Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces. RESULTS: From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up. CONCLUSIONS: This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.

Multi-Criteria-Decision-Analysis (MCDA) for the Horizon Scanning of Health Innovations an Application to COVID 19 Emergency.

Aim: In this article, we aim to present a tool for the early assessment of medical technologies. This evaluation system was designed and implemented by the National Centre for HTA and the National Centre for Innovative Technologies of the Istituto Superiore di Sanita, Italy, in order to respond to an institutional commitment within the "Health Technologies Assessment Team" that was established to face the huge demand for the evaluation of Health Technologies during the pandemic event caused by COVID-19, with a smart and easy-to-use framework. Methods: Horizon scanning was conducted through a brief assessment carried out according to the multicriteria decision analysis methodology. Each HTA domain was attributed a score according to a pros/cons and opportunities/threats system, derived from evidence in the literature. Scores were weighted according to different perspectives. Scores were presented in a Cartesian graph showing the positioning according to the potential value and the perceived risk associated with the technology. Results: Two case studies regarding the early assessment were reported, concerning two specific technologies: an individual protection device and a contact tracking system.

Clinical and Immunological Outcomes in High-Risk Resected Melanoma Patients Receiving Peptide-Based Vaccination and Interferon Alpha, With or Without Dacarbazine Preconditioning: A Phase II Study.

Clinical studies based on novel rationales and mechanisms of action of chemotherapy agents and cytokines can contribute to the development of new concepts and strategies of antitumor combination therapies. In previous studies, we investigated the paradoxical immunostimulating effects of some chemotherapeutics and the immunoadjuvant activity of interferon alpha (IFN-α) in preclinical and clinical models, thus unraveling novel rationales and mechanisms of action of chemotherapy agents and cytokines for cancer immunotherapy. Here, we carried out a randomized, phase II clinical trial, in which we analyzed the relapse-free (RFS) and overall survival (OS) of 34 completely resected stage III-IV melanoma patients, treated with peptide-based vaccination (Melan-A/MART-1 and NY-ESO-1) in combination with IFN-α2b, with (arm 2) or without (arm 1) dacarbazine preconditioning. All patients were included in the intention-to-treat analysis. At a median follow-up of 4.5 years (interquartile range, 15.4-81.0 months), the rates of RFS were 52.9 and 35.3% in arms 1 and 2, respectively. The 4.5-year OS rates were 68.8% in arm 1 and 62.7% in arm 2. No significant differences were observed between the two arms for both RFS and OS. Interestingly, the RFS and OS curves remained stable starting from 18 and 42 months, respectively. Grade 3 adverse events occurred in 5.9% of patients, whereas grade 4 events were not observed. Both treatments induced a significant expansion of vaccine-specific CD8+ T cells, with no correlation with the clinical outcome. However, treatment-induced increase of polyfunctionality and of interleukin 2 production by Melan-A-specific CD8+ T cells and expansion/activation of natural killer cells correlated with RFS, being observed only in nonrelapsing patients. Despite the recent availability of different therapeutic options, low-cost, low-toxic therapies with long-lasting clinical effects are still needed in patients with high-risk resected stage III/IV melanoma. The combination of peptide vaccination with IFN-α2b showed a minimal toxicity profile and resulted in encouraging RFS and OS rates, justifying further evaluation in clinical trials, which may include the use of checkpoint inhibitors to further expand the antitumor immune response and the clinical outcome. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26.

Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000-2007: Results of EUROCARE-5 population-based study.

BACKGROUND: Significant advances in the management of patients with lymphoid and myeloid malignancies entered clinical practice in the early 2000's. The EUROCARE-5 study database provides an opportunity to assess the impact of these changes at the population level by country in Europe. We provide survival estimates for clinically relevant haematological malignancies (HM), using the International Classification of Diseases for Oncology 3, by country, gender and age in Europe. METHODS: We estimated age-standardised relative survival using the complete cohort approach for 625,000 adult patients diagnosed in 2000-2007 and followed up to 2008. Survival information was provided by 89 participating cancer registries from 29 European countries. Mean survival in Europe was calculated as the population weighted average of country-specific estimates. RESULTS: On average in Europe, 5-year relative survival was highest for Hodgkin lymphoma (81%; 40,625 cases), poorest for acute myeloid leukaemia (17%; 57,026 cases), and intermediate for non-Hodgkin lymphoma (59%; 329,204 cases), chronic myeloid leukaemia (53%; 17,713 cases) and plasma cell neoplasms (39%; 94,024 cases). Survival was generally lower in Eastern Europe and highest in Central and Northern Europe. Wider between country differences (>10%) were observed for malignancies that benefited from therapeutic advances, such as chronic myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma and multiple myeloma. Lower differences (<10%) were observed for Hodgkin lymphoma. CONCLUSIONS: Delayed or reduced access to innovative and appropriate therapies could plausibly have contributed to the observed geographical disparities between European regions and countries. Population based survival by morphological sub-type is important for measuring outcomes of HM management. To better inform quality of care research, the collection of detailed clinical information at the population level should be prioritised.

Use of back protector device on motorcycles and mopeds in Italy.

The international scientific literature reports no data on the prevalence and effectiveness of back protector devices (BPD). In Italy, no data have been collected on BPD because their use is not mandatory. To fill this gap, the National Institute of Health implemented a cross-sectional study in collaboration with the National Traffic Police.Accident cases were collected from 1 December 2011 to 25 October 2013. Overall, data from 2104 accidents involving 2319 injured subjects were analysed: 1821 (78.5%) of these were motorcyclists and 498 (21.5%) mopedists. The use of Hard-shell BPD or jackets with airbags in motorcyclists is higher then in moped drivers (16.2% vs 1.3%,P»0.000). Concerning level of protection, there are no differences between drivers and passengers. In most severely injured motorcyclists (i.e. hospitalized or deceased), the percentage of injuries to the spine was lower (13.6%) among those who used a high level safety device (hard-shell BPD and/or airbags) and rose to 27.3% among those who used only protective clothing (P»0.022). When the variables potentially affecting the results of not using a high-safety device were controlled, a bivariate analysis showed that the odds of serious spinal injury were 2.72 times greater (P»0.049) and a multivariate analysis showed that they were 2.81 times greater (P»0.012). This study points out that greater use of BPD could reduce the number of injuries to the spinal column resulting from road traffic accidents involving motorized two-wheeled vehicles.

Development of a pilot project on data sharing among partners of the Italian Hub of Population Biobanks (HIBP): association between lipid profile and socio-demographic variables.

The Italian Hub of Population Biobanks (HIBP) includes both ongoing and completed studies that are heterogeneous in both their purpose and in the specimens collected. The heterogeneity in starting conditions makes sharing study data very difficult because of technical, ethical, and collection rights issues that hamper collaboration and synergy. With the aim of overcoming these difficulties and establishing the "proof-of-concept" that sharing studies is achievable among Italian collections, a data-sharing pilot project has been agreed to by HIBP members. Participants agreed to the general methodology and signed a shared Data Transfer Agreement. The biobanks involved were: EURAC (Micros study), CIG (GEHA project), CNESPS (FINE, MATISS, MONICA, OEC1998, ITR (Italian Twin Register), and IPREA studies, and MOLIBANK (Moli-Sani project). Biobank data were uploaded into a common database using a dedicated informatics infrastructure. Demographic data, and anthropometric and hematochemical parameters were shared for each record. Each biobank uploaded into the common database a dataset with a minimum of 1000 subjects, for a total of 5071 records. After a harmonization process, the final dataset included 3882 records. Subjects were grouped into three main geographic areas of Italy (North, Center, and South) and separate analyses were performed for men and women. The 3882 records were analyzed through multivariate logistic regression analysis. Results were expressed as odds ratios with 95% confidence interval. Results show several geographical differences in the lipidemic pattern, mostly regarding cholesterol-HDL, which represents a strong basis for further, deeper sample-based studies. This HIBP pilot study aimed to prove the feasibility of such collaborations and it provides a methodological prototype for future studies based on the participation in the partnership of well-established quality collections.

Biobank networking: the European network initiative and the italian participation.

The evolution of the Biobanking and Biomolecular Resources Infrastructure, planned as a federated network of biological resources centers including all types of repositories of biological materials of human origin, toward a legal consortium of European Union Member States is described. The inception of Biobanking and Biomolecular Resources Infrastructure gave a strong impetus to the reorganization of the Italian biobanks both with the formation of structured specific networks of disease-oriented biobanks as well as with the establishment of biobank networks with a regional constituency. This complex articulation requires a strong central coordination that the Health Minister entrusted to the Istituto Superiore di Sanità.

The EUROCARE-4 database on cancer survival in Europe: data standardisation, quality control and methods of statistical analysis.

This paper describes the collection, standardisation and checking of cancer survival data included in the EUROCARE-4 database. Methods for estimating relative survival are also described. Incidence and vital status data on newly diagnosed European cancer cases were received from 93 cancer registries in 23 countries, covering 151,400,000 people (35% of the participating country population). The third revision of the International Classification of Diseases for Oncology was used to specify tumour topography and morphology. Records were extensively checked for consistency and compatibility using multiple routines; flagged records were sent back for correction. An algorithm assigned standardised sequence numbers to multiple cancers. Only first malignant cancers were used to estimate relative survival from registry, year, sex and age-specific life tables. Age-adjusted and Europe-wide survival were also estimated. The database contains 13,814,573 cases diagnosed in 1978-2002; 92% malignant. A negligible proportion of records was excluded for major errors. Of 5,753,934 malignant adult cases diagnosed in 1995-2002, 5.3% were second or later cancers, 2.7% were known from death certificates only and 0.4% were discovered at autopsy. The remaining 5,278,670 cases entered the survival analyses, 90% of these had microscopic confirmation and 1.3% were censored alive after less than five years' follow-up. These indicators suggest satisfactory data quality that has improved since EUROCARE-3.

The ISS Carcinogens Data Bank (BDC).

The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.

The ISS Sensitizing Agents Data Bank (BDS).

The Istituto Superiore Sanità has developed a data bank on sensitizing substances (Banca Dati Sensibilizzanti, BDS), available on website (www.iss.it/bdse/), sharing complete, controlled and updated information coming from different sources, such as scientific publications, international agencies and governmental or non governmental organizations. It is worthwhile that the main objective of the BDS is not the classification of sensitizing or potentially sensitizing agents within specific risk classes, but it is essentially to provide concise and non confidential information related to this endpoint. At present, the BDS includes: all the substances officially classified by European Union, (Annex I to Directive 67/548/EEC), some substances listed in I (Directive 67/548/EEC) for endpoints different than "sensitization" but indicated as sensitizers by other relevant institutions, all the substances indicated as sensitizers by relevant agencies or institutions (ACGIH, DFG), some substances indicted as sensitizers by industry and other non-governmental organizations (ETAD and HERA), all the substances regarded as "potentially sensitizing dyes" by the Commission of the European Community for the award of the eco-label to textile products, some substances for which, even in the absence of any categorization by Union, ACGIH or DFG, it is not possible to exclude a sensitizing potential on the basis of reliable documents.

The ISS Reclamation Data Bank.

Since the issue of the first regulations concerning the remediation of contaminated sites, the Istituto Superiore di Sanità, on the basis of specific requests, has drawn up various technical opinions regarding the proposed reference values (quality standards) for soils and underground waters, to be achieved when remediating contaminated sites, for substances for which no standard limit values did not exist at that time. These reference values, widely used throughout the country and accepted and adopted as "remediation aim" values by various territorial bodies responsible for the approval and monitoring of remediation projects, have been collected in a specific reclamation oriented data bank known as the "Banca Dati Bonifiche (BDB)" (Reclamation Data Bank). The BDB contains the related standardized "rationale" for each reference value, in order to serve as a useful reference for the national bodies concerned with the remediation of contaminated sites.

Surveillance of toxic exposures: the pilot experience of the Poison Control Centers of Milan, Pavia and Bergamo in 2006.

Between 1 February and 31 March 2006, the Poison Control Centers (PPC) active in Lombardy collaborated with an integrated surveillance system carried out in Piedmont during the Olympic Games 2006. The collaborating PPC notified to the system 697 human cases of exposure occurred in Piedmont during the observation period. Among these cases, 70% were exposed accidentally, 40% were 6 years old or younger, and 45% reported at least a clinical effect. The agents more frequently reported were: cleaning substances (household) (110 cases), fumes/gases/vapors (63 cases, comprising 38 cases accidentally exposed to carbon monoxide), and sedative/hypnotics/antipsychotics (53 cases). Although very limited, the available observations focused the attention on specific hazards and were able to highlight the potential of a toxic exposure surveillance system based on the information reported by the Italian PPC.