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Objective: In a scenario of new expensive cancer therapies entering the market, strategies of optimisation and cost containment are crucial in oncology care. Better management of drug waste and centralization of drug preparation can be effective strategies to achieve these goals. The aim of this work is to describe the economic management of a high cost anticancer drug (ipilimumab) in some Italian reference centres. Methods: This was an observational, multicentred study in which economical and clinical data of 21 cancer centres (418 patients) were collected during the enrollment period from February 2013 to August 2014. The follow-up period ended in July 2015. Results: Participants purchased 10.7% more vials of ipilimumab than necessary for compounding. The results were variable among centres, and only five centres had a deviation lower than 5% between the drug purchased and the drug prescribed. Hospitals applying the drug day reached a statistically significant residual of drug effectively used compared to the amount prescribed (P = 0.018). Consequently, the price for treating a model patient was significantly lower in those hospitals (median spare of 7456 euro per patient). Conclusions: This study demonstrated that the careful management of drug waste and the application of drug-day, through a proper selection of vial and the ability to use the leftover drug, can generate economic savings. However, tailoring the drug stock to clinical need is still an open issue which deserves further analysis. [ABSTRACT FROM AUTHOR]

This work focuses on the clinical-organizational model implemented in an Italian region (Liguria) to streamline the access procedures to galenic cannabis preparations. The competent local health care authority that takes care of tracing a virtuous path to obtain common, uniform and shared protocols and ensure high standards of care is A.Li.Sa. (Azienda Ligure Sanitaria), a public organization with the function of coordination, direction and governance of the health care in the regional hospitals and health facilities. To this purpose, different working groups and a board meeting have been set up with the main role to define and develop technical standards to be applied to the prescription, preparation and dispensing of pharmaceutical forms based on therapeutic cannabis. In particular, the galenic preparations provided by the Italian Ministry of Health, described in detail in the regional standard operating protocols, are described and discussed. Moreover, the most significant data monitored from 2018 to 2020 and collected by hospitals and the evaluation of those derived from local pharmacies and health facilities are presented, discussed and compared in regards to their adherence and coherence with the Italian Institute of Health (ISS) data.

Monoclonal antibodies, such as bamlanivimab and etesevimab combination (BEC), have been proposed for patients with mild or moderate coronavirus disease 2019 (COVID-19). However, few studies have assessed the factors associated with the early administration of BEC or the impact of early BEC treatment on the clinical evolution of the patients. We conducted a retrospective cohort study of all adults with COVID-19 who received BEC at three institutions in the Liguria region. The primary endpoint was to investigate the clinical variables associated with early BEC infusion. Secondary endpoints were 30-day overall mortality and the composite endpoint of requirement of hospital admission or need for supplemental oxygen during the 30-day follow-up period. A total of 127 patients (median age 70 years; 56.7% males) received BEC. Of those, 93 (73.2%) received BEC within 5 days from symptoms onset (early BEC). Patients with a higher Charlson comorbidity index were more likely to receive early treatment (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.04-2.45; p = 0.03) in contrast to those reporting fever at presentation (OR 0.26, 0.08-0.82; p = 0.02). Early BEC was associated with lower likelihood of hospital admission or need for supplemental oxygen (OR 0.19, 0.06-0.65; p = 0.008). Five patients who received early BEC died during the follow-up period, but only one of them due to COVID-19-related causes. Early bamlanivimab and etesevimab combination was more frequently administered to patients with a high Charlson comorbidity index. Despite this, early BEC was associated with a lower rate of hospital admission or need for any supplementary oxygen compared to late administration. These results suggest that efforts should focus on encouraging early BEC use in patients with mild-moderate COVID-19 at risk for complications.

Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16). In situ , TAF express detectable levels of epidermal growth factor receptor (EGFR); thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46 + CD3 - NK cells, enriched in CD16 + cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46 + CD3 - cells were able to kill autologous TAF; in vivo , this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF) of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy.

About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: Medication errors in oncology may cause severe damage to patients, professionals, and the environment. The Italian Ministry of Health issued Raccomandazione 14 to provide guidelines for prevention of errors while using antineoplastic drugs. This work aimed at analyzing Raccomandazione 14 through the different viewpoints of the hospital pharmacist, the nurse, the oncologist, and the hospital director., Methods: Twenty-seven Italian healthcare organizations participated in a self-assessment survey evaluating compliance with Raccomandazione 14 within the oncology, hematology, and pharmacy departments., Results: The self-assessment results showed a general acknowledgement of the need for centralized management of anticancer agents. The specific responsibility of the pharmacist on the centralized management of anticancer drugs from preparation to disposal emerged as a critical point. The nurse, beyond the skills in drug administration and prevention of extravasation, also plays a fundamental role in educating and supporting the patient. The physicians, who are attentive to scientific, clinical, and regulatory criteria in prescribing and monitoring the therapies, are called upon to improve awareness on the importance of sharing standardized procedures with other professionals, to minimize medication error occurrence. The implementation of a complete computerized management from prescribing to drug administration and follow-up was highlighted. Multidisciplinary groups were constituted across the nation by professionals dedicated to the implementation of electronic health records and drug history and medical reconciliation processes., Conclusions: Our analysis of the Ministerial Raccomandazione 14 urges implementation of the resources for ensuring quality and safety during prescription, preparation, and administration of anticancer drugs.

Background: Insulin-like growth factor-1 (IGF-1) promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R). Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3), which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes., Methods and Results: Besides inducing apoptosis, concentrations of doxorubicin comparable to those observed in patients after bolus infusion (0.1-1 µM) caused a progressive decrease in IGF-1R and increase in IGFBP-3 expression. Exogenous IGF-1 was capable to rescue cardiomyocytes from apoptosis triggered by 0.1 and 0.5 µM, but not 1 µM doxorubicin. The loss of response to IGF-1 was paralleled by a significant reduction in IGF-1 availability and signaling, as assessed by free hormone levels in conditioned media and Akt phosphorylation in cell lysates, respectively. Doxorubicin also dose-dependently induced p53, which is known to repress the transcription of IGF1R and induce that of IGFBP3. Pre-treatment with the p53 inhibitor, pifithrin-α, prevented apoptosis and the changes in IGF-1R and IGFBP-3 elicited by doxorubicin. The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol., Conclusions: Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to doxorubicin-initiated apoptosis. Further studies are needed to confirm these findings in human cardiomyocytes and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading pathogen causing nosocomial infections. Many studies have shown that the restricted use of antibacterials is associated with a decline in resistance. To establish whether an intervention protocol designed to limit the use of cephalosporins can lower mRSA infection rates and impact on Gram-negative bacteria susceptibility in an intensive Care Unit (ICU), we conducted a prospective, non-randomized, before-after intervention study in an 18-bed ICU in Genoa, Italy. The intervention was a hospital antibiotic control policy and the observation was routine monitoring for nosocomial infections and antibiotic use, recording periodically the incidence density and MRSA prevalence. The intervention included a new antibiotic guideline that restricted the use of cephalosporins for all ICU inpatients. The analysis showed that the intervention determined a significant reduction in cephalosporin usage (-70.3%), while fluoroquinolones, mainly ciprofloxacin, increased after introduction of the antibiotic policy (+46.5%). A significant reduction in the percentage of MRSA infections (-30%) and heterogeneous susceptibility patterns in Klebsiella pneumoniae and Pseudomonas aeruginosa were noted.

Background: Considering their long experience acquired during the period October 1981 and October 2001 related to the treatment of 1,000 patients suffering from anal fistulas, the authors reasses the problem of this affection from an etiopathogenic, classifying, diagnostic and therapeutic point of view., Methods: Surgical treatment of Arnous's French School was performed; these methods foresee the division of the operative times and slow sphincteric sectioning by an elastic constriction., Results: Results were excellent: 99.2% of complete recoveries and very few failures and complications: 0.5% incomplete recovery, 0.3% relapse, 1.3% soiling, 1.5% gas temporary incontinence., Conclusions: The main premise to obtain the patient's recovery is to perform a faultless technique and to follow assiduously and minutely the long postoperative period of surgical wounds.

Crohn's disease is not a homogeneous clinical entity but may shows many clinical pictures during its period, prognosis and response to therapy. Anal and perianal localisations are frequently found; they can occur isolated, months or years in advance the disease, or can be concomitant with an ileal, colic or rectal involvement. There can be many kinds of lesions: simple, such as eczema or fissuration, complex, such as high rectal or rectovaginal fistulas. A rational classification of anal and perianal manifestations is suggested. Local medical therapy, is very effective in minor lesions, and has to be associated with systemic medical therapy particularly nowadays: the knowledge on phlogosis, biology and biotechnology revolution, have launched a new therapeutic era. Surgical therapy can be performed only in case of complex disease non responsive to medical therapy or when it is necessary to give a rest to anorectal tract. To perform a correct follow-up, considering unpredictability of lesions, a careful clinical evaluation and an intensive surveying plan associated with objective evaluation parameters are suggested.

Objective: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use., Methods: Usage and expenditure data for all antibiotics were collected from 1996 to 1998. Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days. Cost data were expressed in Euros. Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT). were initiated. The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant., Results: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998. The control program resulted in overall savings of 342,927 Euros after the first year of implementation. The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03). Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings. In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use., Conclusion: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital. Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.

The possible dermatological and proctologic causes, of Pruritus Ani that often, due to its persistence and for its consequent lesions of scratching, becomes a real disease, are analysed. Particular attention is given to therapeutical treatment, describing which hygienic-dietetic rules must be followed and which treatments can be utilised, if the cause of the symptom is known and if it is possible to remove it or not. Moreover, personal experience on 312 patients examined in twelve years is reported.