Effectiveness of Caplacizumab Nanobody in Acquired Thrombotic Thrombocytopenic Purpura Refractory to Conventional Treatment.

Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses.

Analysis of chemical contamination by hazardous drugs with BD HD Check® system in a tertiary hospital.

The presence of contamination in the healthcare work environment by one of the types of hazardous drugs, cytostatics, has been found in multiple international studies. Recent studies and guidelines recommend surface monitoring for risk assessment of healthcare professionals' exposure. The availability of detection techniques is critical to successfully carry out this type of monitoring. The use of new semi-quantitative techniques allows quicker results. The main objective of this study was to determine the existence of hazardous drugs on the working surfaces in different locations of a tertiary hospital using the BD HD Check® semi-quantitative device. The presence of methotrexate, doxorubicin and cyclophosphamide was analysed at 80, 89 and 82 locations in 10, 13 and 11 clinical units, respectively. A total of 251 samples were analysed. The monitoring results were positive for 13.1% of the analysed samples, with 36.3% of the methotrexate samples, 0% of the doxorubicin samples and 4.9% of the cyclophosphamide samples. Mapping the presence of HD in our hospital has allowed us to evaluate the effectiveness of controls established in the hospital to minimise the exposure of healthcare professionals to hazardous drugs. The speed in obtaining results has enabled immediate corrective actions in cases where contaminated surfaces were detected.

Tall man lettering application in medication information systems as a quality and safety strategy in hospital organization.

WHAT IS KNOWN AND OBJECTIVE: The technique of highlighted capital letters, Tall Man lettering, is a tool that allows differentiating the names of similar drugs in a way that contributes to reduce medication errors related to the drug identification. The objective was to implement and monitor the application protocol of the Tall Man lettering tool in drug information systems in the healthcare environment to improve the quality of care and patient safety in the pharmacy service and the medical institution. METHODS: Scope: Tertiary general hospital with 1000 beds in which a Tall Man lettering application protocol was approved in the pharmacy service information systems. DESIGN: Retrospective observational study. PERIOD: 2019-2021. POPULATION: Information systems and databases used in the pharmacy service. Working group: Made up of people in charge of information areas and systems. IMPLEMENTATION: Five phases were defined: organization of the working group, selection of drug names and information systems, establishment of actions, their execution, and results monitoring. VARIABLES: Number of pharmaceutical specialties, names of active ingredient and brands incorporated in the information systems. RESULTS AND DISCUSSION: The application of Tall Man lettering was authorized in 13/13 information systems, six have been fully implemented and seven are in the database update phase. Of the implanted systems, a total of 210 drug names have been modified (168/210 active ingredient and 42/210 brand names), corresponding to 659 pharmaceutical specialties. WHAT IS NEW AND CONCLUSION: The application of Tall Man lettering in hospital information systems is a tool for improving the quality of the pharmacy service and guarantees the safety of medicines in the hospital.

A multi-criteria decision analysis on the value of nintedanib for interstitial lung diseases.

OBJECTIVES: Our aim was to assess the value of nintedanib for non-idiopathic progressive fibrosing interstitial lung disease (non-IPF PF-ILD) and systemic sclerosis-associated ILD (SSc-ILD) in the Spanish context, using a multi-criteria decision analysis (MCDA). METHODS: Following an adaptation of the Evidence and Value: Impact on DEcision Making (EVIDEM) MCDA methodology, the estimated value of nintedanib was obtained by means of an additive linear model that combined individual weights (100-points distribution) of criteria with the individual scoring of nintedanib in each criterion for every indication, assigned by a multidisciplinary committee of twelve clinicians, patients, pharmacists, and decision-makers. To assess the reproducibility, an alternative weighting method was applied, as well as a re-test of weights and scores at a different moment of time. RESULTS: The experts committee recognized nintedanib as an intervention with a positive value contribution in comparison to placebo for the treatment of non-IPF PF-ILD (0.50 ± 0.16, on a scale from -1 to 1) and SSc-ILD (0.40 ± 0.12), diseases which were considered as very severe and with high unmet needs. The drug was perceived as a treatment that provides an added therapeutic benefit for patients (0.06-0.07), given its proven clinical efficacy (0.05-0.06), slight improvements in patient-reported outcomes (0.01-0.02), and similar safety profile than placebo (-0.04-0.00), which will likely be positioned as a recommended therapy in the next clinical practice guidelines updates. CONCLUSIONS: Under this increasingly used methodology, nintedanib has shown to provide a positive value estimate for non-IPF PF-ILD and SSc-ILD when compared to placebo in Spain.

Adherence and adverse events of intraperitoneal chemotherapy in optimally debulked ovarian cancer patients: Real-life study.

PURPOSE: Intraperitoneal with intravenous chemotherapy (IP/IV) is the recommended option for patients with stage III cancer with optimally debulked (<1 cm residual) disease based on randomized controlled trials and showing important improvements in overall survival and progression free survival. However, its application has not been largely adopted due to its difficult administration that requires a trained nurse staff. The aim of this work was to study the completion and the toxicity of an IP outpatient chemotherapy regimen in optimally debulked stage III ovarian cancer patients. METHODS: A single-center, retrospective observational study in women with stage III ovarian cancer following optimal cytoreductive surgery (<1 cm) followed by IP/IV chemotherapy from 2009 to 2017. The IP/IV regimen was as it follows: IV paclitaxel 175 mg/m2 in 3 h, day 1; IP cisplatin (100 mg/m2-until December 2013-or 75 mg/m2), day 2; IP paclitaxel 60 mg/m2, day 8, each 21 days for six cycles. RESULTS: A total of 60 patients received IP/IV regimen. Of these, 41 patients (68.3%) completed the six IP chemotherapy cycles and 51 (84.9%) completed four or more cycles. Most of the adverse events reported were non-hematological and G1-2. There was no difference neither in adherence nor in the frequency of adverse events between both cisplatin groups. Despite a high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer.

Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn's Disease.

INTRODUCTION: The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. OBJECTIVE AND METHODS: To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn's disease (CD) patients. RESULTS: Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 µg/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 µg/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 µg/g, -respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 µg/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 µg/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman's rho correlation, 0.440; p < 0.05). CONCLUSIONS: IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD.

Impact of voriconazole plasma concentrations on treatment response in critically ill patients.

WHAT IS KNOWN AND OBJECTIVE: Several authors have demonstrated the relationship between voriconazole concentrations and the risk of therapeutic failure and adverse events However, the information about voriconazole concentrations in the critically ill patient is scarce. The aim of this study was to analyse the plasma concentrations and pharmacokinetic behaviour of voriconazole in critically ill patients and their association with the treatment response and development of toxicity. METHODS: A prospective, observational study was conducted. Patients admitted to an intensive care unit and on treatment with intravenous voriconazole were included. Plasma concentrations were measured between days 4 and 7 from the start of the treatment. The pharmacokinetic analysis was performed using the NONMEM® software. A regression model was used to evaluate the variables associated with the values outside the therapeutic range, as well as the relationship between the plasma concentrations and the treatment response and the development of hepatotoxicity. RESULTS AND DISCUSSION: A total of 33 patients were included. Plasma concentrations outside the therapeutic range (1-5.5 mg/L) were observed in 15 patients, being above the established range in 9 (27.3%) cases, and below it in 6 (18.2%) cases. The presence of a bilirubin value of >1.5 mg/dL and a C-reactive protein >100 mg/dL was associated with supra-therapeutic concentrations. Voriconazole concentrations greater than 5.5 mg/dL were associated with the development of hepatotoxicity. WHAT IS NEW AND CONCLUSIONS: There is a wide variation in voriconazole concentrations in critically ill patients, being associated with a high frequency of adverse events. Close monitoring of these values is required in order to decrease the risk of therapeutic failure and toxicity.

Salvage therapy with topical posaconazole in lung transplant recipients with invasive Scedosporium infection.

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplantation, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present 3 complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplantation. In 2 of 3 cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid® device was used for nebulized therapy. Topical posaconazole was well tolerated in 2 patients, with only a slight cough during administrations; the third patient had local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical PSZ as salvage therapy for resistant mold infections in lung transplant recipients. These 3 cases represent the entire experience using this approach; no additional patients have received this therapy due to there not having been any additional cases of Scedosporium tracheobronchitis presented.

Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

OBJECTIVE: The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. METHODS: Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. RESULTS: Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. CONCLUSION: The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.

Drug Interaction Between Oral Cyclosporine Modified and Iron.

OBJECTIVE: To describe a recent case of suspected interaction between oral cyclosporine modified and iron. CASE SUMMARY: A 33-year-old man underwent urgent cardiac transplantation for refractory cardiogenic shock caused by acute myocarditis. The patient had persistently low levels of cyclosporine despite a dose increase of the drug after the change of administration route from intravenous to oral. Spacing the administration of cyclosporine modified from oral iron resolved the problem. This drug interaction was reported as "probable" as determined by a Drug Interaction Probability Scale score of 7. Using this scoring system, the patient experienced a probable drug interaction between cyclosporine and iron both administered orally, and we surmise that the mechanism is that iron physicochemically destabilizes the cyclosporine microemulsion when both are administered concurrently. DISCUSSION: This may be because of the interaction between cyclosporine microemulsion and iron because this cation can destabilize the immunosuppressant dosage form. CONCLUSIONS: Taking into account that joint administration of oral iron and cyclosporine modified can generate a physicochemical interaction that involves a decrease in the absorption of cyclosporine modified, we believe that it is necessary to recommend spacing administrations of both drugs as well as monitoring levels of cyclosporine in order to ensure optimal levels of immunosuppression.

[Experience in the management of immunosuppressant treatment with hepatitis C virus protease inhibitors]. / Experiencia en el manejo de inmunosupresores con los fármacos inhibidores de proteasa frente al virus de la hepatitis C.

INTRODUCTION: Antiviral drugs for the treatment of hepatitis C virus (HCV) infections have a large number of interactions. The aim of this study was to describe the interactions of telaprevir, boceprevir and sofosbuvir with immunosuppressive drugs in liver transplant recipients. METHODS: A retrospective observational study was performed in liver transplant patients with HCV infection who started treatment with telaprevir, boceprevir or sofosbuvir. Dose, regimens and plasma levels of tacrolimus, cyclosporine and sirolimus before and after antiviral treatment initiation were collected. Average variations in dose, dosing interval and immunosuppressive plasma levels after the start of treatment were calculated. RESULTS: Thirty-five patients were included. In patients treated with telaprevir (n = 18), the cyclosporine dose was reduced by an average of 59.1% (SD = 14.6%), yielding an average reduction of 14.6% (18.8%) in plasma levels. The dose of tacrolimus was reduced by 34.3% (31.7%), increasing the dosing interval by a mean of 73.4 (38.2) hours. After this variation, tacrolimus levels were increased by an average of 59.7% (89.6%). In patients treated with boceprevir (n = 4), tacrolimus started with a reduction of 18.1% (9.8%) of the initial dose and an average increase in the dosing interval of 12.0 (16.9) hours, showing a mean reduction in plasma levels of 37.7% (21.8%). Sofosbuvir therapy (n = 13) showed no significant variations in immunosuppressive drug levels. CONCLUSIONS: The interaction of telaprevir and boceprevir with immunosuppressive drugs requires a substantial dose reduction at the beginning of treatment and close monitoring of plasma levels.

Presence of good humanization practices in the healthcare of patients with rare diseases in Pharmacy Services. / Presencia de buenas prácticas de humanización en la atención a los pacientes con enfermedades raras en los servicios de farmacia.

OBJECTIVE: To analyze the presence of Good Humanization Practices in the care of patients with rare diseases in Hospital Pharmacy Services and to identify the strengths and prevalent areas for improvement in the humanization of healthcare. METHODS: Online questionnaire structured in two parts was developed using Google Form®. The first one was designed to collect identifying data and the second one included questions related to compliance with the 61 standards of the Manual of Good Humanization Practices in the healthcare of patients with rare diseases in Hospital Pharmacy Services. Access to the questionnaire was sent by email to the Heads of the Hospital Pharmacy Service of 18 hospitals. The study period was from October 2021 to October 2022. The analyzed variables were the number of criteria that were considered met, total compliance (percentage of criteria met), by strategic line and by type or level of standard, globally and grouped by regions of Spain. RESULTS: 18 Hospital Pharmacy Services were included. The overall mean of standards met was 31.1 (95% CI: 24.8-37.6) and mean total compliance was 52.1% (95% CI: 44.4-59.7). The mean compliance by strategic line was line 1 Humanization culture: 46.5% (95% CI: 35.3-57.7), line 2 Patient empowerment: 47.4% (95% CI: 37.1- 57.8), line 3 Professional care: 49.7% (95% CI: 39.8-59.1), line 4 Physical spaces and comfort: 55.6% (95% CI: 46.3-64.8) and line 5 Organization of healthcare: 63.8% (95% CI: 55.8-71.9). CONCLUSION: The average compliance with the standards is between 40 and 60%, which indicates that humanization is present in the Hospital Pharmacy Services, but there is a wide margin for improvement. The main strength in the humanization of Hospital Pharmacy Services is a patient-centered care organization, and the area with the greatest room for improvement is the culture of humanization.

Real world effectiveness and safety of nivolumab in patients with relapsed or refractory classical hodgkin lymphoma. / Efectividad y seguridad en vida real de nivolumab en pacientes con linfoma de hodgkin clásico en recaída o refractario.

OBJECTIVE: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy. METHOD: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival and overall survival. Safety was measured as percentage of patients with adverse effects and severity. RESULTS: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2.0-4.5), including autologous hematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3.0-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%) and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95%CI: 0-49.1), median overall survival was not reached. At the study cutoff date, five patients had died (38.5%), four were in complete remission without active treatment (30.8%) and four were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, two suffered treatment delays (thrombocytopenia and hypertransaminemia) and one changed the regimen to monthly (pulmonary toxicity). CONCLUSIONS: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed in the study sample favorable effectiveness data, expressed as objective response rate of 46.2% and clinical benefit of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature.

New challenges of advanced therapies. / Nuevos retos de las terapias avanzadas.

The huge development that Advanced Therapy Medicinal Products (AMTPs) have experienced in recent years, both commercial and research, represent a challenge for Hospital Pharmacy at all levels. The aim of this article is to describe the implementation of an Advanced Therapies Unit (AUT) and the process of preparation of the AMTPs according to the "good manufacturing practices" (GMP), as well as the results obtained in a tertiary hospital, as an example of the challenges posed by MTA's academic production. The AUT meets the requirements established in the GMP by guaranteeing that the medicines produced therein are of the quality required for the use for which they are intended, and also provides support to various research groups involved in the development of AMTPs. The AUT is composed of a highly qualified multidisciplinary team, qualified and trained in GMP, and is authorized for the preparation of five types of AMTPs consisting of allogeneic virus-specific T cells (VST) with various viral specificities. A circuit has been established in collaboration between the UTA and the Pharmacy Service with the Hematology Service for the assessment of the clinical indication, the request and preparation of VST, which allows the treatment of patients receiving hematopoietic stem cell transplants who present viral reactivations resistant or refractory to standard treatment, or who cannot tolerate it due to toxicity. Preliminary results from these AMTPs suggest that VSTs are an effective and safe alternative. Academic AMTPs have special interest in orphan indications or in the absence of alternative treatments, and their production through the "hospital exemption" can favor early access in the initial phases of development and at a lower cost. It is essential to promote the training of hospital pharmacists in GMP and their participation in collaboration with other clinicians and researchers to develop AMTPs that meet all logistical and regulatory requirements.

[Translated article] New challenges in advanced therapies.

The huge development that advanced therapy medicinal products (AMTPs) have experienced in recent years, both commercial and research, represent a challenge for hospital pharmacy at all levels. The aim of this article is to describe the implementation of an advanced therapies unit (AUT) and the process of preparation of the AMTPs according to the "good manufacturing practices" (GMP), as well as the results obtained in a tertiary hospital, as an example of the challenges posed by MTA's academic production. The AUT meets the requirements established in the GMP by guaranteeing that the medicines produced therein are of the quality required for the use for which they are intended, and also provides support to various research groups involved in the development of AMTPs. The AUT is composed of a highly qualified multidisciplinary team, qualified and trained in GMP, and is authorized for the preparation of 5 types of AMTPs consisting of allogeneic virus-specific T cells (VST) with various viral specificities. A circuit has been established in collaboration between the UTA and the pharmacy service with the hematology service for the assessment of the clinical indication, the request, and preparation of VST, which allows the treatment of patients receiving hematopoietic stem cell transplants who present viral reactivations resistant or refractory to standard treatment, or who cannot tolerate it due to toxicity. Preliminary results from these AMTPs suggest that VSTs are an effective and safe alternative. Academic AMTPs have special interest in orphan indications or in the absence of alternative treatments, and their production through the "hospital exemption" can favor early access in the initial phases of development and at a lower cost. It is essential to promote the training of hospital pharmacists in GMP and their participation in collaboration with other clinicians and researchers to develop AMTPs that meet all logistical and regulatory requirements.

Toxic-metabolic encephalopathy induced by metronidazole and disulfiram: classics never die.

A 53-year-old male with recovering alcohol dependency, diagnosed with bipolar disorder and recurrent episodes of diverticulitis, came to the emergency department with disorientation and confusion after 3 days of treatment with metronidazole 250 mg/12 hours and ciprofloxacin 500 mg/12 hours for acute diverticulitis. In the hospital emergency department, he presented moments of agitation, fluctuations of attitude, increased basal tremor, with rhythmic movement of the left arm and leg, as well as generalised rigidity with an episode of tonic-clonic seizure of 1.5-2 min duration. After performing different diagnostic tests, significant brain findings were ruled out. The pharmacy department recommended the discontinuation of one of the two drugs. As a result, the on-call doctor adjusted the patient's treatment: disulfiram and previous antibiotic therapy (metronidazole and ciprofloxacin) were discontinued, and amoxicillin/clavulanic acid 2 g/8 hour was prescribed instead. The patient progressed well and fully recovered.

Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety.

Isavuconazole is used to treat fungal infections. This study aims to describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy and patient safety. We conducted a prospective, observational study in patients treated with intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) and 12 h (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. The relationship between plasma concentration and clinical and microbiological outcomes and safety was evaluated. The influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes and extracorporeal devices: continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO)) was analysed. Population pharmacokinetic modelling was performed using NONMEN®. A total of 71 isavuconazole samples from 24 patients were analysed. The mean Cmin was 1.76 (1.02) mg/L; 87.5% reached the optimal therapeutic target and 12.5% were below 1 mg/L. Population pharmacokinetics were best described by a one-compartment model with first-order elimination. No factor had a significant impact on the plasma concentration or pharmacokinetic parameters. Thus, isavuconazole could be safely used in a critically ill population, even in those treated with CRRT and ECMO, from a pharmacokinetic standpoint. Therefore, routine therapeutic drug monitoring may not be strictly necessary in daily clinical practice.

Selective ophthalmic intra-arterial melphalan therapy for advanced retinoblastoma: implementation and outcomes of a new chemotherapy protocol.

Retinoblastoma is a relatively uncommon childhood tumor. If untreated, RB grows to fill the eye and destroys the ocular globe's internal architecture. Metastatic spread usually begins after the first 6 months, and death occurs within a matter of years. When treated, overall survival rounds 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localized treatment. In our hospital, pediatric oncologists asked the Pharmacy Department for assessment in order to implement a new chemotherapy protocol for the treatment of advanced intraocular elegible retinoblastoma cases using melphalan administered directly through the ophthalmic artery. In this paper, we describe the protocol implementation carried out by our collaborative interdisciplinary team as well as the clinical outcomes of five cases treated with ophthalmic intra-arterial melphalan therapy. Oncology pharmacists can contribute with their knowledge to the implementation process of new collaborative practice protocols recommending doses, predicting possible adverse effects and assessing about drug stability and elaboration, packaging and administration methods.

Omics-Based Approaches for the Characterization of Pompe Disease Metabolic Phenotypes.

Lysosomal storage disorders (LSDs) constitute a large group of rare, multisystemic, inherited disorders of metabolism, characterized by defects in lysosomal enzymes, accessory proteins, membrane transporters or trafficking proteins. Pompe disease (PD) is produced by mutations in the acid alpha-glucosidase (GAA) lysosomal enzyme. This enzymatic deficiency leads to the aberrant accumulation of glycogen in the lysosome. The onset of symptoms, including a variety of neurological and multiple-organ pathologies, can range from birth to adulthood, and disease severity can vary between individuals. Although very significant advances related to the development of new treatments, and also to the improvement of newborn screening programs and tools for a more accurate diagnosis and follow-up of patients, have occurred over recent years, there exists an unmet need for further understanding the molecular mechanisms underlying the progression of the disease. Also, the reason why currently available treatments lose effectiveness over time in some patients is not completely understood. In this scenario, characterization of the metabolic phenotype is a valuable approach to gain insights into the global impact of lysosomal dysfunction, and its potential correlation with clinical progression and response to therapies. These approaches represent a discovery tool for investigating disease-induced modifications in the complete metabolic profile, including large numbers of metabolites that are simultaneously analyzed, enabling the identification of novel potential biomarkers associated with these conditions. This review aims to highlight the most relevant findings of recently published omics-based studies with a particular focus on describing the clinical potential of the specific metabolic phenotypes associated to different subgroups of PD patients.

Consensus recommendations for the improvement of inter- and intra-centre care coordination in the management of hemophilia. / Consenso de recomendaciones para la mejora de la coordinación asistencial inter e intra-centros en el abordaje de la hemofilia.

OBJECTIVE: Define consensus recommendations to improve care coordination between Hospital Pharmacy, Haematology and Nursing, inter- and intra-center, in the care of haemophilia patients. METHOD: Recommendations for the improvement of care coordination in the management of haemophilia patients were identified and assessed by a multidisciplinary panel of professionals with experience in this field (Hospital Pharmacy, Haematology and Nursing) and supported by scientific evidence. The identified recommendations were assessed by Rand/UCLA consensus methodology (Delphi-adapted) based on their appropriateness and, subsequently, on their necessity. In both cases, it was used ordinal Likert scale. Data were statistically analysed through different metrics. RESULTS: Fifty-three recommendations for the improvement of care coordination between Hospital Pharmacy, Haematology and Nursing in the management of haemophilia patients were identified, grouped into eight areas of action: i) Haemophilia units, reference centers and multidisciplinary care; ii) Role of Haematology, Hospital Pharmacy and Nursing in the patient journey of haemophilia patients; iii) Telepharmacy and telemedicine; iv) Pharmacokinetic monitoring; v) Transition to adult patient regimen; vi) Patient health education; vii) Surgery, emergency room and hospital admission; and viii) Outcome evaluation. All recommendations were assessed as appropriate and necessary by the external expert panel. CONCLUSIONS: Haemophilia patient journey is complex and depends on different variables. It also requires the involvement of different healthcare professionals who must act in a coordinated and integrated manner at all stages of the patient's life, adapted to their individual needs. On this matter, the identified and agreed recommendations may improve continuity and quality of care, as they facilitate the integration and coordination of the professionals involved in the management of this pathology, especially Hospital Pharmacy, Haematology and Nursing.