Adherence to oral chemotherapy: Evidence from a randomised clinical trial.

OBJECTIVE: To evaluate the efficacy of a reinforcement message (RM) administered by a hospital pharmacist on adherence, through a randomised study involving patients undergoing oral chemotherapy from which an objective outcome measure and patients' subjective opinions were collected. A secondary aim was to detect which psychological or clinical factors influence adherence. METHODS: Forty patients were enrolled and randomised to an experimental group (EG) or a control group (CG). The EG received a 10-minute RM provided by a hospital pharmacist with a doctor and a nurse. The CG received the standard of care. To measure adherence, plasma drug concentration and subjective evaluation were taken during the visits, in addition to a psychological assessment (coping strategies, psychological distress and personality traits). RESULTS: The EG reported higher drug levels and a statistically significant higher mean score on the subjective evaluation. A linear regression model highlighted statistically significant differences in the plasma drug concentration, after considering toxicity and dose reduction and controlling for the Reward Dependence Scale of the Temperament and Character Inventory between the EG and the CG. CONCLUSION: Adequate information and education on the therapy, using an RM strategy provided by a hospital pharmacist, seems to positively influence adherence to the treatment.

Medicine recovery and reuse in a hospital setting: a lesson from Italy.

OBJECTIVES: In 2017, a new programme was created for recovering and reusing (i) unexpired Class A medicines (i.e. dispensed either by community pharmacies or by hospitals) in hospital settings and (ii) medicines for hospital use only (Class H). The aim of this study was to describe a three-year reuse programme and assess its impact on medicines cost savings. METHODS: The setting was AOU Città della salute e della Scienza-in Turin (Italy). All the collected data referred to packages of medicines collected by/assigned to AOU for reuse over the 1 December 2017/1 December 2020 period. Retail prices were used to calculate the financial value of the medication. Costs for the time required for the reuse programme (a working group comprising a pharmacist, an administrative and a warehouse worker) were estimated. KEY FINDINGS: A total of 10 450 boxes were recovered for reuse (corresponding to 52% of donated boxes). The total value was €1 300 000. Class H accounted for 73% (€952 000) of the total value of the recovered medicines, while they represented only 9% of the packages collected by/assigned to AOU. Estimated cost for the reuse programme was €75 806. CONCLUSIONS: Medicine recycling programmes with appropriate checks can be implemented to facilitate reuse of medications in hospital settings. This study provides evidence that a reuse programme reduced drug expenditures, especially regarding the Class H medications. These results contribute to the debate regarding opportunity for recycling and sustainability in medicines management.

Sorafenib maintenance after hematopoietic stem cell transplantation improves outcome of FLT3-ITD-mutated acute myeloid leukemia.

In a retrospective analysis, 21 acute myeloid leukemia patients receiving single-agent sorafenib maintenance therapy in complete remission (CR) after hematopoietic stem cell transplantation (HSCT) were compared with a control group of 22 patients without maintenance. Sorafenib was initiated a median of 3 months (IQR: 2.3-3.5) after allogeneic HSCT with a median daily dosage of 400 mg (range: 200-800) orally, and lasted a median of 11.3 months (IQR: 3.3-24.4). No significant increase in graft versus host disease or toxicity was observed. Adverse events were reversible with dose adjustment or temporary discontinuation in 19/19 cases. With a median follow-up of 34.7 months (IQR: 16.9-79.5), sorafenib maintenance significantly improved cumulative incidence of relapse (p = 0.028) as well as overall survival (OS) (p = 0.016), especially in patients undergoing allogeneic HSCT in CR1 (p < 0.001). In conclusion, sorafenib maintenance after allogeneic HSCT is safe and may improve cumulative incidence of relapse and OS in FLT3-ITD-mutated AML.

Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma.

Background: The anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019. Methods: We conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs. Results: A total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol. Conclusions: Our findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.

Use of exogenous pulmonary surfactant in acute respiratory distress syndrome (ARDS): Role in SARS-CoV-2-related lung injury.

Several pre-clinical and clinical trials show that exogenous pulmonary surfactant has clinical efficacy in inflammatory lung diseases, especially ARDS. By infecting type II alveolar cells, COVID-19 interferes with the production and secretion of the pulmonary surfactant and therefore causes an increase in surface tension, which in turn can lead to alveolar collapse. The use of the pulmonary surfactant seems to be promising as an additional therapy for the treatment of ARDS. COVID-19 causes lung damage and ARDS, so beneficial effects of surfactant therapy in COVID-19-associated ARDS patients are conceivable, especially when applied early in the treatment strategy against pulmonary failure. Because of the robust anti-inflammatory and lung protective efficacy and the current urgent need for lung-supportive therapy, the exogenous pulmonary surfactant could be a valid supportive treatment of COVID-19 pneumonia patients in intensive care units in addition to the current standard of ARDS treatment.

Ozone therapy in COVID-19: A narrative review.

The main objective of this narrative review is to describe the available evidence on the possible antiviral activity of ozone in patients with COVID-19 and its therapeutic applicability through hospital protocols. Amongst different possible therapies for SARS-CoV-2 pneumonia, ozone therapy seems to have an immunological role because of the modulation of cytokines and interferons, including the induction of gamma interferon. Some data suggest the possible role of ozone therapy in SARS, either as a monotherapy or, more realistically, as an adjunct to standard treatment regimens; therefore, there is increasing interest in the role of ozone therapy in COVID-19 treatment The PubMed and Scopus databases and the Italian Scientific Society of Oxygen Ozone Therapy website were used to identify articles focused on ozone therapy. The search was limited to articles published from January 2011 to July 2020. Of 280 articles found on ozone therapy, 13 were selected and narratively reviewed. Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses. Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs. Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage. The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation. Systemic ozone therapy seems useful in controlling inflammation, stimulating immunity and as antiviral activity and providing protection from acute coronary syndromes and ischaemia reperfusion damage, thus suggesting a new methodology of immune therapy. Systemic ozone therapy in combination with antivirals in COVID-19-positive patients may be justified, helpful and synergic.

Impact of Allogeneic Stem Cell Transplantation on Testicular and Sexual Function.

High-dose chemotherapy and radiotherapy, administered as a conditioning regimen before stem cell transplantation, are known to negatively impact testicular function and sexuality. However, to date, only a few studies have simultaneously analyzed the real prevalence of these complications in this clinical setting. Therefore, this study aimed to assess the prevalence of testicular dysfunction and sexual impairment in a cohort of males who underwent allogeneic stem cell transplantation in adulthood. This observational, cross-sectional, single-center study consecutively enrolled 105 subjects on outpatient follow-up. Testicular function and sexuality were evaluated through a hormonal profile (testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B) and the IIEF-15 questionnaire, respectively. We found a higher prevalence of hypogonadism (21%), impaired spermatogenesis (87%), and erectile dysfunction (72%) compared with the general population. Chronic graft-versus-host disease, especially of moderate/severe grade, was associated with an increased risk of developing erectile dysfunction (odds ratio, 6.338). Moreover, a high proportion of patients presented with alterations in all domains of sexual function, even after complete clinical remission of hematologic disease. Our data confirm both testicular function and sexuality alterations as frequent complications after allogeneic stem cell transplantation. A multidisciplinary approach is advisable for early diagnosis and adequate treatment.

Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life.

BACKGROUND: The use of dasatinib and nilotinib in the treatment of patients with chronic myeloid leukemia represents a valid therapeutic option for patients resistant or intolerant to imatinib. In this multicentre study, adherence, persistence and efficacy in real life over two years of treatment were evaluated. MATERIALS AND METHODS: Adherence to treatment was calculated as the ratio between the dose received and the prescribed dose. The dose received was calculated using pharmacy refill data. The persistence with treatment was calculated as the difference between the end and the beginning of the treatment. Efficacy was assigned as Progression-Free Survival (PFS) and Events-Free Survival (EFS) and represented through the Kaplan-Meier curve. RESULTS: The number of patients analysed was 117, 70 treated with dasatinib and 47 with nilotinib. Adherence to treatment for dasatinib and nilotinib at two years was 0.91 and 0.82 respectively. Persistence at two years was 77% while the PFS was 92% for both drugs in the study. CONCLUSION: Adherence to the treatment calculated over two years showed a superiority of dasatinib over nilotinib. Nevertheless, the efficacy in terms of PFS and EFS is superimposable between the two drugs in the study.

Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents.

A series of 25 compounds, some of which previously were described as inhibitors of human liver microsomal oxidosqualene cyclase (OSC), were tested as inhibitors of Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana OSCs expressed in an OSC-defective strain of S. cerevisiae. The screening identified three derivatives particularly promising for the development of novel anti-Trypanosoma agents and eight derivatives for the development of novel anti-Pneumocystis agents.