[Translated article] Have changes concerning carboplatin and anthracyclines been incorporated?

OBJECTIVE: Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv). METHODS: Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out. RESULTS: 61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods. CONCLUSIONS: Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.

Antiemetic guidelines: Have we incorporated the changes concerning carboplatin and anthracyclines? / Guías antieméticas: ¿hemos incorporado los cambios referentes a carboplatino y antraciclinas?

OBJECTIVE: Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv). METHODS: Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out. RESULTS: 61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods. CONCLUSIONS: Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.

Successful Integration of Clinical Pharmacists in an OPAT Program: A Real-Life Multidisciplinary Circuit.

Outpatient parenteral antimicrobial therapy (OPAT) programs encompass a range of healthcare processes aiming to treat infections at home, with the preferential use of the intravenous route. Although several barriers arise during the implementation of OPAT circuits, recent cumulative data have supported the effectiveness of these programs, demonstrating their application in a safe and cost-effective manner. Given that OPAT is evolving towards treating patients with higher complexity, a multidisciplinary team including physicians, pharmacists, and nursing staff should lead the program. The professionals involved require previous experience in infectious diseases treatment as well as in outpatient healthcare and self-administration. As we describe here, clinical pharmacists exert a key role in OPAT multidisciplinary teams. Their intervention is essential to optimize antimicrobial prescriptions through their participation in stewardship programs as well as to closely follow patients from a pharmacotherapeutic perspective. Moreover, pharmacists provide specialized counseling on antimicrobial treatment technical compounding. In fact, OPAT elaboration in sterile environments and pharmacy department clean rooms increases OPAT stability and safety, enhancing the quality of the program. In summary, building multidisciplinary teams with the involvement of clinical pharmacists improves the management of home-treated infections, promoting a safe self-administration and increasing OPAT patients' quality of life.

Financial impact of the hospital pharmacy's participation in clinical trials.

OBJECTIVES: To estimate the cost of the hospital pharmacy's participation in clinical trials (CTs) and to compare it to the amount received in compensation from sponsors.To analyse the financial impact of CTs that end without recruiting any patients and without any financial compensation from promoters. METHODS: This retrospective observational study analysed data from 5 years (2014-2018) at a tertiary university hospital.We established an allocation formula taking into account direct costs related to the pharmacy department's CT area's activity (reception, safekeeping, preparation, devolution, and destruction of medication, as well as patient monitoring) and indirect costs (facilities, resources, support staff). We calculated the costs to the department and the compensation received both overall and based on the type of promoter, clinical department involved in the trial, and the number of patients included. RESULTS: We included 134 trials. Costs added up to €207 372.95 and the compensation to €149 128.93 (€58 244.02 loss for the department). Trials ending without recruiting patients (33.6%) and without compensation accounted for 57.45% of the deficit. The mean cost of trials ending without recruiting patients was €875. We plan to charge a reimbursable setup fee for opening CTs to safeguard against these losses (€875 for trials in all departments except oncology; €1100 for oncology because 38% of their trials end without recruiting patients) and to compensate for the costs incurred in participating in trials for cooperative groups without financial compensation (20%). CONCLUSIONS: Billing sponsors based on costs incurred for each trial would be a fairer system than the current approach based on the number of patients included. Establishing an initial fee would make up for losses from trials that fail to recruit any patients.

Hypertensive crisis following the administration of tedizolid: possible serotonin syndrome.

Thiscase report concerns a 34-year-old male with a hip prosthesis infection, under treatment with antidepressant and antihypertensive drugs, who presented with an increase in blood pressure after four days of treatment with oral tedizolid. Tedizolid was discontinued, and the dose of antihypertensive was increased. The patient progressively achieved the normalisation of blood pressure values, which allowed a reduction in the antihypertensive agent dose to its usual regimen. No cases of hypertension or serotonin toxicity are described in the initial tedizolid studies, where patients treated with other serotonergic drugs were excluded. However, this does not mean that these effects may not occur in clinical practice, especially in patients under concomitant treatment with this type of medication, because of the greater risk of drug interactions. The causality of this suspected drug reaction was analysed and it was considered as possible. The case has been reported to the pharmacovigilance system.

Evidence supporting regulatory-decision making on orphan medicinal products authorisation in Europe: methodological uncertainties.

BACKGROUND: To assess uncertainty in regulatory decision-making for orphan medicinal products (OMP), a summary of the current basis for approval is required; a systematic grouping of medical conditions may be useful in summarizing information and issuing recommendations for practice. METHODS: A grouping of medical conditions with similar characteristics regarding the potential applicability of methods and designs was created using a consensus approach. The 125 dossiers for authorised OMP published between 1999 and 2014 on the EMA webpage were grouped accordingly and data was extracted from European Public Assessment Reports (EPARs) to assess the extent and robustness of the pivotal evidence supporting regulatory decisions. RESULTS: 88% (110/125) of OMP authorizations were based on clinical trials, with 35% (38/110) including replicated pivotal trials. The mean (SD) number of pivotal trials per indication was 1.4 (0.7), and the EPARs included a median of three additional non-pivotal supportive studies. 10% of OMPs (13/125) were authorised despite only negative pivotal trials. One-third of trials (53/159) did not include a control arm, one-third (50/159) did not use randomisation, half the trials (75/159) were open-label and 75% (119/159) used intermediate or surrogate variables as the main outcome. Chronic progressive conditions led by multiple system/organs, conditions with single acute episodes and progressive conditions led by one organ/system were the groups where the evidence deviated most from conventional standards. Conditions with recurrent acute episodes had the most robust datasets. The overall size of the exposed population at the time of authorisation of OMP - mean(SD) 190.5 (202.5) - was lower than that required for the qualification of clinically-relevant adverse reactions. CONCLUSIONS: The regulatory evidence supporting OMP authorization showed substantial uncertainties, including weak protection against errors, substantial use of designs unsuited for conclusions on causality, use of intermediate variables, lack of a priorism and insufficient safety data to quantify risks of relevant magnitude. Grouping medical conditions based on clinical features and their methodological requirements may facilitate specific methodological and regulatory recommendations for the study of OMP to strengthen the evidence base.