Paola Crosasso

Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.

Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.

CP-106 A case study of syndrome of inappropriate antidiuretic hormone secretion: Alternative treatment to tolvaptan with urea and sodium chloride

Background The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a frequent cause of hyponatraemia consisting of a reduction in plasma sodium concentration values below 135 mEq/L. This condition, reducing the survival of the patient, extends the duration of the hospital stay and therefore increases the cost for a given patient. Purpose To provide an alternative treatment to the use of tolvaptan, either to enable cost savings and to maintain a good quality of life for patients by raising plasma sodium values, and consequently lowering the cost of hospitalisation. Material and methods 3 patients were perorally administered urea and sodium chloride (NaCl) capsules to treat SIADH. All were affected by small cell lung cancer and were receiving chemotherapy (carboplatin). We speculated that NaCl and urea should be as effective as tolvaptan.1 We evaluated the patient’s natraemia four times, and the cost of the pharmacist’s performances for the preparation of 30 g of urea and 2 g of NaCl capsules. Results The natraemia was normalised after treatment administration, as shown in table 1. With NaCl and urea treatment, effectiveness was achieved, despite carboplatin therapy and the patient’s medical condition which are both well known causes of SIADH.Abstract CP-106 Table 1 Patient No 1 Patient No 2 Patient No 3 Baseline (mEq/L) 131 131 122 Control 1 (mEq/L) 138 142 136 Control 2 (mEq/L) 145 140 136 Control 3 (mEq/L) 135 135 137 Control 4 (mEq/L) 139 139 136 Treatment with tolvaptan 15 g or 30 g costs 70€ per day, compared with 6.6€ for NaCl 2 g with 30 g of Urea. The patients did not need hospitalisation due to hyponatraemia. Conclusion These preliminary data may indicate that therapy based on oral administration of urea and NaCl is as effective as tolvaptan in the treatment of SIADH. This new treatment approach being less aggressive and cheaper, may be interesting for further investigations regarding this therapeutic alternative. References and/or Acknowledgements Soupart A, Coffernils M, Couturier B, et al. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH No conflict of interest.

Invasive fungal infections: observational study in two hospitals in Italy (Turin) and France (Paris)

Background Invasive fungal infections (IFIs) constitute a frequent and important complication in modern medicine and represent a relevant problem in the matter of the management of hospitalised and immunocompromised patients. The most common fungal infections, candidiasis and aspergillosis, are an important cause of morbidity and mortality in critically ill and immunocompromised patients: therefore, in spite of pharmacological development, they are still difficult to treat and to eradicate. Purpose Because the pharmacist, as a member of the multidisciplinary team, can contribute by checking the treatment prescribed, to reduce medication related problems, we conducted an observational study of IFIs in two hospitals, one in Italy (Turin) and the other in France (Paris), to give a picture of the differences in their distribution and therapeutic approach in two hospital realities. Material and methods The study was conducted using a clinical database of patients between 2012 and 2013; patients were stratified according to infection, sex, age, wards and therapy. Results Candida or aspergillus related IFIs were detected in 213 men and 107 women. Candidiasis was higher in the critical care unit (Turin 40% vs Paris 48%), prevalent in men Turin 78%; Paris 65%) and older patients (61–90 years old), with a prevalence of 67% in Turin and 49% in Paris. In France, aspergillosis was highly distributed in the critical care unit (42%) and in the haematology ward (38%), was prevalent in men (68%) and, unlike candidiasis, in younger patients (47%; 31–60 years old). A comparable study was not possible for Turin where only one systemic aspergillosis was diagnosed. The most widely used drug in both hospitals was caspofungin, followed by fluconazole in Turin and voriconazole in Paris. Conclusion A similar trend in candidiasis related IFIs, with no significant differences between the two hospitals, was detected. Conversely, there were differences in the use of drugs. To reduce the incidence and mortality rate of IFI, the therapeutic approach should take account of the epidemiological picture but the hospital pharmacist’s role is also important. In fact, the hospital pharmacist together with the hospital infections committee, can monitor and analyse consumption, perform epidemiological statistics and choose the best therapy for patients in terms of cost and efficacy. No conflict of interest.

DI-071 Everolimus (AFINITOR): a case of steatosis in the treatment of pancreatic neuroendocrine tumours

Background Everolimus (Afinitor) is an inhibitor of mTOR (mammalian target of rapamycin), which has demonstrated antineoplastic activity in breast, renal and neuroendocrine pancreatic cancer. At our centre, an uncommon adverse drug reaction (ADR) was detected in a patient treated with everolimus and lanreotide. The patient started lanreotide treatment on July 2013 and, after chemoembolization of hepatic nodules, everolimus 10 mg/day was added. After 5 months, Nuclear Magnetic Resonance (NMR) showed massive steatosis involving the entire left lobe of the liver and part of the right lobe, with no signs of recurrence of neoplastic disease. Treatment with everolimus was stopped. Purpose To describe an uncommon adverse drug reaction to everolimus and lanreotide, review the literature and search for cases in National and European ADR databases. Material and methods Searches of the Italian National Pharmacovigilance Network (I-NPN) and Eudravigilance databases and of PubMed and Embase databases were performed for reports of steatosis related to everolimus and lanreotide treatment. The Naranjo algorithm was applied to our case. Results Searches of literature databases retrieved a single case report of steatosis related to everolimus treatment. No reports were detected in I-NPN. Eudravigilance Database contains 5 cases of steatosis possibly related to treatment with everolimus. According to the Naranjo algorithm, the causal link for our case appears to be “possible”. Conclusion Our case has a “possible” causal link according to the Naranjo algorithm and the patient is now on NMR follow up. Treatment for his pancreatic neuroendocrine tumour is now based on lanreotide. The detection and follow up of this uncommon ADR has been possible thanks to the close and constant collaboration between Oncology Endocrinologists and Pharmacists and is an important contribution to defining the safety profile of everolimus in patients with pancreatic neuroendocrine tumours. Reference Schieren G, Bölke E, Scherer A, et al. Severe everolimus-induced steatohepatis: a case report. Eur J Med Res 2013;18:22. doi: 10.1186/2047-783X-18-22 No conflict of interest.

GM-017 The impact on pharmaceutical expenditure of non-profit clinical trials with lenalidomide

Background The hospital has an important national role in the conduct of non-profit clinical trials. These represent 58% of the studies approved in 2012 and about 5% of them involve the use of lenalidomide Purpose To define the cost savings that conducting non-profit clinical trials could generate for the Hospital and the NHS, focusing on the evaluation of innovative high-cost medicines such as lenalidomide Materials and methods Five active trials involve the use of lenalidomide. A cost evaluation was conducted on these studies in terms of what it would cost the Hospital, comparing three different scenarios: if the patients were enrolled in a non-profit clinical trial treated off-label with lenalidomide given gold standard treatment Results It costs the hospital 23,500 € to treat the patients enrolled in the clinical trials considered. Lenalidomide is provided free by the pharmaceutical company. 3,963,409 € is the cost of lenalidomide that the company should claim for the enrolled patients. Such expenditure is supposed to be borne by the regional health system and then the hospital as the use is considered off-label. 2,288,646 € is the average cost of therapeutic alternatives suggested by NHS guidelines. The medicines used most and which would produce this increase in expenditure are thalidomide and bortezomib. Conclusions The analysis shows that in the first case the expense for patient treatment appears paltry compared to the other two scenarios. This result emphasises the importance of non-profit clinical trials, which may also represent a tool that can reduce the expense of high-cost medicines. This also allows patients to be treated according to innovative regimens, giving them new chances that would be denied had we followed NHS guidelines rigidly. No conflict of interest.

PS-070 Audits of non-profit clinical trials: pharmacists promote high quality research

Background Checking is essential to ensure the quality of clinical data while a clinical trial is in progress. This process promotes adherence to GCP as defined: Guidance for Industry Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring – FDA Reflection paper on risk-based quality management in clinical trials – EMA Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products – MHRA Purpose To demonstrate that Quality Assessment (QA) is essential to ensure the quality of non-profit research. Materials and methods The QAs path is developed through Quality Assurance (QA) and Quality Control (QC) audits. All trials are given a risk class that defines the methods and timing of intervention. That risk class is obtained by creating a table within a specific matrix. The card brings together some 81 parameters that characterise the experiment. The audit activity at the centre is scheduled only for studies belonging to risk class III-IV. During the QA and QC checklists are used: Risk Management QA Risk Management QC whose elaboration in a separate matrix allows the re-programming. QA activities refers to all practices that were approved from 1 January 2011 to 31/12/2012, because processing is done every six months. Results To date, a risk class has been assigned to 53 studies, of which 34 are active. All centres have been subjected to at least one QA or QC check, in order to eliminate the deviations and violations and comply with the quality requirements defined by GCP. 30 studies required a second QA check and 17 studies required quality control. 6 studies still needed a third revision of QA and 9 studies a second quality control. During the audit it was found that 41% of the studies did not comply with GCP regarding management of the Investigator’s File, for 22% to do with compliance with the SOP, for 21% to do with compilation of the CRF, 11% IMP (investigational medicinal product) management and accounting, 6% regarding reporting of adverse events and 11% compared to the protocol. The risk class of the studies after the audit has remained the same, except for one study, which was terminated early because of the increased risk, and for 3 class 3 studies that were so well run the risk class was reduced. Conclusions Usually, two audits were sufficient for full compliance with the requirements defined in the GCP. This project improved the protection of the subjects, increased the quality and integrity of data and got rid of practices and processes that did not add value to the clinical trial (s), thus optimising the efficiency of monitoring. Through intelligent allocation of resources for monitoring trials, sponsors have the opportunity to realise significant time and cost savings while maintaining or even increasing quality. No conflict of interest.

New galenic formulation based on mechloretamine for topical treatment of mycosis fungoides

Background The treatment of mycosis fungoides (MF), the most common form of primary cutaneous lymphoma T cells, depends on clinical staging. In the presence of lesions in patch/plaque the use of phototherapy, retinoids, immunomodulators and radiotherapy is common in the early stages and in the presence of disseminated nodular lesions the use of systemic chemotherapy. Purpose The possibility to have a preparation of topical chemotherapy available, which can be used alone or in combination with other treatments, could be an important therapeutic option. Thus topical formulations of mechlorethamine with characterisation and evaluation stability were developed. The authors then proceeded to the evaluation of the clinical activity and the tolerability of the topical preparation based mechlorethamine 0.02% in the treatment of plaque and nodular lesions of MF. Materials and Methods Various lipophilic and hydrophilic formulations were prepared and characterised. Mechlorethamine 0.02% in Aquaphor ointment base was identified and characterised for chemical and microbiological stability for clinical investigation. After informed consent, 6 patients, median age 67 years (48 -88), whose disease had relapsed after chemotherapy were treated. The galenic preparation was applied daily for the treatment of 11 lesions, 5 days / week for up to 3 weeks. The response was evaluated after treatment using the RECIST criteria. Results The use of mechlorethamine has been improved in order to obtain a new preparation technique in consideration of instrumental resources available in a hospital pharmacy and the difficulty of handling cytostatic drugs for topical formulations. 11 lesions were treated, a partial clinical response was obtained in 5 and a complete response in 2. In all the cases, the treatment was well tolerated, 2 patients developed short-lived erythema / oedema peri-lesional. There was no evidence of systemic toxicity. Conclusions Based on these preliminary results, topical application of mechlorethamine has been well tolerated and associated with good clinical activity. The encouraging results obtained in this preliminary phase encouraged us to continue the study on a larger number of patients.