Assessing the risk of using hazardous drugs in Hospital-at-Home Units: a big data study protocol.

OBJECTIVE: This article describes a study protocol for the implementation of quality and traceability control in the hazardous  medication circuit through an analysis of risks and the development and  introduction of a Big Data-based software application aimed at performing  a continuous and dynamic audit of the whole system. Method: A standardized graphical modeling tool called Business Process Model Notation will be used to generate a detailed description of each of the stages in the hazardous medication circuit with a view to  ensuring full traceability of the system. The information on each stage will  be collected in a flowchart, which will be used -together with each event's likelihood of occurrence and severity- as a basis to calculate the  criticality index of the different control points established and to determine  any control measures that may be required. The flowcharts will  also be used to develop the technological support needed to capture  all such data as may be relevant to the model. Proper quality control of the process will be ensured by client software agents intended to allow  automatic applica tion of efficient data processing tools at the different  phases. In addition, Big Data methodologies, in particular machine  learning, will be used to develop algorithms based on the repository of  generated data to come up with patterns capable of improving the  protocols to be applied. Lastly, proper operation of the process will be  ensured by means of clinicalpharmaceutical verification and a full  technical-documentary review of control and registration systems. CONCLUSIONS: The development of a risk management system based on  mobile technology will allow integration of hazardous drugs into a standardized system, ensuring the safety, quality, and traceability of the hazardous medication handling process.

Objetivo: Describir el protocolo del estudio para la instauración del control del proceso de los medicamentos peligrosos que asegure la calidad y su trazabilidad, mediante el análisis de riesgos, desarrollando e  Implantando una herramienta informatizada que, gracias a la utilización de técnicas de big data, permita conocer y auditar el conjunto del sistema de  forma continua y dinámica.Método: Mediante los procesos de notación gráfica normalizada Business Process Model Notation se desarrollarán los flujogramas  Específicos que permitan conocer las etapas del proceso de los  Medicamentos peligrosos que determinen la trazabilidad total del sistema.  Cada una de las etapas será recogida en los cuadros de gestión, donde a  través de la probabilidad del suceso y su gravedad se calculará el índice de criticidad de cada punto de control que se determine, y se establecerán las medidas de control. A partir de los cuadros de gestión se desarrollará el  soporte tecnológico para la captura de todos los datos que sean  pertinentes al modelo. Para asegurar el control de la calidad del proceso se optará por agentes software cliente, que permitan en fases posteriores  aplicar herramientas eficientes en el procesamiento de datos de modo  automático. A partir de aproximaciones metodológicas del big data, y en  particular del ámbito de machine learning, se desarrollarán algoritmos  sobre el repositorio de datos generado para poder obtener patrones que  permitan mejorar los protocolos de aplicación. Por último, para asegurar el funcionamiento del proceso se realizará la verificación clínico-farmacéutica  y la revisión completa, técnico-documental, de los sistemas de control y  registro.Conclusiones: La generación del sistema de gestión de riesgos mediante  tecnología móvil permitirá integrar los medicamentos peligrosos en un sistema normalizado, con el fin de mejorar la seguridad, calidad y  trazabilidad del proceso de manipulación de los medicamentos peligrosos.

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer.

OBJECTIVE: To determine the effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in patients with non-small  cell lung cancer. METHOD: This is a retrospective observational study including patients treated in second line and beyond. The effectiveness of treatment  was assessed by means of overall survival and progression free survival  measurements. Toxicity was described according to the Common Criteria  for Adverse Event Terminology v5.0. RESULTS: The study included 8 patients treated with atezolizumab,19 with nivolumab, and 16 with pembrolizumab. Median progression free  survival with atezolizumab was 9.6 months (95%CI 2-17.2), 12.6 months (95%CI 6.9-18.2) for nivolumab, and 8.5 months (95%CI 0-19)  for pembrolizumab. Median overall survival was 13.4 months (95%CI 6- 20.9) for nivolumab. Both PFS and OS were statistically higher in patients  with grade 0-1 metastasis in the case of nivolumab, and in ECOG 0-1  patients for pembrolizumab. Median overall survival was not reached for  atezolizumab or pembrolizumab. Around 85% of patients suffered adverse  effects of some degree. Two of the patients treated with nivolumab  developed vitiligo. Overall survival of both was higher than 2.5 years. CONCLUSIONS: For the patients included in the sample, nivolumab was less  effective in those with two or more metastases; the effectiveness of pembrolizumab was lower in ECOG-2 patients. Vitiligo was related to a more durable response to treatment.

Objetivo: Efectividad y seguridad de atezolizumab, nivolumab y  embrolizumab en cáncer de pulmón no microcítico metastásico.Método: Estudio observacional retrospectivo en pacientes con cáncer de  pulmón no microcítico metastásico tratados en segunda línea o posteriores. La efectividad fue evaluada mediante supervivencia global y  supervivencia libre de progresión. La toxicidad mediante los Criterios Comunes de Terminología de Efectos Adversos v5.0.Resultados: Se incluyeron 8 pacientes con atezolizumab, 19 con  nivolumab y 16 con pembrolizumab. La mediana de supervivencia libre de progresión con atezolizumab fue 9,6 meses (intervalo de confianza del 95% [IC95%] 2-17,2), 12,6 meses (IC95% 6,9-18,2) para nivolumab 8,5 meses (IC95% 0-19) para pembrolizumab. La mediana de  supervivencia global con nivolumab fue 13,4 meses (IC95% 6-20,9) y no  se alcanzó para atezolizumab y pembrolizumab. Ambas fueron superiores  para los pacientes con 0-1 metástasis para nivolumab y en los pacientes  con ECOG 0-1 para pembrolizumab. Alrededor de un 85% de los pacientes sufrieron efectos adversos. Dos pacientes tratados con  nivolumab experimentaron vitíligo, con una supervivencia global mayor de  2,5 años.Conclusiones: En la muestra analizada, la efectividad de nivolumab es  menor en pacientes con dos o más metástasis, y la de pembrolizumab es  menor en pacientes con ECOG 2. La aparición de vitíligo se relacionó con  una respuesta duradera.

Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes.

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a "converter phenotype," which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies. Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed. Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected. Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Observational study of clinical toxicity with different formulations of docetaxel in breast cancer patients.

OBJECTIVE: To analyze the excipients and impurities contained in the various docetaxel products available on the market and find out  whether they may be responsible for any of the different adverse events  associated with the use of docetaxel in patients with breast cancer  receiving adjuvant or neoadjuvant treatment. METHOD: This is a prospective, multicenter, longitudinal observational, study carried in 26 hospitals in Madrid, Catalonia, Andalusia, and the Valencia Region. The different docetaxel formulations were  characterized in terms of their pH, amount of the active ingredient and  impurities. The cumulative incidence of adverse events of any grade was  evaluated. Adverse events were stratified by drug type and differences  were analyzed by means of a chi-square test. RESULTS: Statistically significant differences were found between the different docetaxel formulations in the cumulative per-cycle incidence of: dosage change, anemia, hypersensitivity reactions and  anaphylaxis, neuropathy, palmoplantar and dermal toxicity, ungual toxicity  and facial edema. The formulation with the lowest content of impurities  showed better results in terms of change of dosage, visits to the  emergency room and incidence of anemia and facial edema. However, it  was associated with poorer results regarding hospitalization, febrile  neutropenia, motor neuropathy and palmoplantar toxicity. CONCLUSIONS: The results of the study showed differences in the incidence of adverse events of the different docetaxel products available in  Spain. Such differences were statistically significant for some of the  variables analyzed. The study was not able to determine which of the  products offered the best toxicity profile. Nor was it possible to establish a  correlation with respect to the composition of excipients or the content of  impurities.

Objetivo: Estudiar los excipientes e impurezas de los diferentes  medicamentos comercializados de docetaxel y conocer la incidencia de  los diversos eventos adversos derivados del uso de docetaxel y su  repercusión clínica en pacientes con cáncer de mama en el contexto de  adyuvancia o neoadyuvancia.Método: Estudio observacional, longitudinal, prospectivo y multicéntrico en 26 hospitales de Madrid, Cataluña, Andalucía y  Comunidad Valenciana. Se caracterizaron las distintas formulaciones de  docetaxel en cuanto a pH, cantidad de docetaxel e impurezas. Se evaluó  la incidencia acumulada de eventos adversos de cualquier grado  estratificados por tipo de medicamento, analizando las diferencias  mediante el test de χ2.Resultados: Se detectaron diferencias estadísticamente significativas entre las distintas formulaciones de docetaxel en cuanto a  la incidencia acumulada por ciclo de: modificación de dosis, anemia,  reacciones de hipersensibilidad y anafilaxia, neuropatía, toxicidad palmo- plantar y dermatológica, toxicidad ungueal y edema facial. La  formulación con un menor contenido en impurezas presentó mejores  resultados en modificación de dosis, visitas a urgencias, e incidencia de  anemia y edema facial, pero peores en hospitalización, neutropenia  febril, neuropatía motora y toxicidad palmo-plantar.Conclusiones: Los resultados muestran diferencias en la incidencia de  los eventos adversos de los distintos medicamentos con docetaxel comercializados en nuestro país, con diferencias significativas  entre ellos en algunas de las variables estudiadas. No se ha podido  identificar un medicamento con un mejor perfil de toxicidad. Tampoco se  ha podido establecer su relación con respecto a la composición de  excipientes e impurezas.

Consensus to identify the dangerous drugs risks in hospital pharmacy services.

OBJECTIVE: To identify the hazards and define the theoretical  occupational risks arising from the process of handling hazard drugs in  hospital pharmacy services on the basis of expert consensus. METHOD: An expert consensus was conducted (nominal group and documentary techniques) using a mixed method of two face-to-face rounds (meeting of participants and approval of proposals) and  three masked rounds (individualized review). The analysis was applied  to the field of hospital pharmacy. The stages of the process were  designed using the standardized graphical Business Process Model and Notation. RESULTS: A specific flowchart was obtained for the management and  traceability of hazardous drugs. All general process phases were  characterized. A management chart included operations addressing the  reception and storage, compounding, conservation, and dispensation of  hazardous drugs in hospital pharmacy services. This chart provides a  description of the chemical hazards and exposure routes. CONCLUSIONS: The hazardous drug process should be integrated in a standard management system to improve the safety of patients and  healthcare professionals. Efficiency can maximized and procedural  incidents minimized, thereby ensuring the quality and the safety of  hazardous drugs handling in hospital pharmacy services. Once hazards  are identified, risk assessment should be implemented using a  systematic and preventative methodology to minimize the risk and  severity of any adverse event.

Objetivo: Identificar los peligros y definir los riesgos laborales teóricos derivados del proceso de manipulación de los medicamentos  peligrosos en los servicios de farmacia hospitalaria mediante un  consenso de expertos.Método: Se realizó un consenso de expertos (grupo nominal y técnicas documentales) utilizando un método mixto mediante dos  rondas presenciales (reunión de los participantes y aprobación de  propuestas) y tres rondas enmascaradas (revisión del material de forma individual). El análisis se aplicó al ámbito de la farmacia hospitalaria y  las etapas del proceso se diseñaron mediante notación gráfica  normalizada Business Process Modeling Notation.Resultados: Se obtuvo el diagrama de flujo específico para la gestión y trazabilidad de los medicamentos peligrosos, caracterizándose cada  una de las fases del proceso general, recopiladas en un cuadro de  gestión de etapas y operaciones de recepción y almacenamiento,  elaboración, conservación y dispensación de medicamentos peligrosos  en los servicios de farmacia hospitalaria, que sirvió para la posterior  descripción de riesgos químicos y vías de exposición.Conclusiones: Los medicamentos peligrosos deben integrarse en un sistema normalizado de gestión con el fin de mejorar la seguridad del paciente y de los profesionales sanitarios, a la vez que se maximizan la eficiencia de los recursos y minimizan los incidentes procesales,  garantizando la calidad y la seguridad del proceso de manipulación de  medicamentos peligrosos en los servicios de farmacia. Sería deseable,  una vez se han identificado los peligros, llevar a cabo una evaluación de  los riesgos siguiendo una metodología sistemática y de abordaje  preventivo que permita calibrar la probabilidad de ocurrencia y la  gravedad de cualquier suceso adverso.

Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain.

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting. Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded. Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4-6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious. Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

Variability of carboplatin dose calculation methods in Spain.

OBJECTIVE: To describe and analyze the variability in carboplatin dosing strategies in Spanish hospitals. METHODS: We designed a questionnaire consisting of 19 multiple-choice items structured in two sections (hospital characteristics and carboplatin dosing data). The questionnaire was sent by e-mail to all the oncology pharmacists included in the register of the Spanish Oncology Pharmacy Group (GEDEFO), and we analyzed the completed questionnaires. RESULTS: Response rate was 33.5% from a total of 185 pharmacy services invited to take part in the survey. All hospitals used the Calvert formula to calculate carboplatin dose with glomerular filtration rate estimated by a formula, most commonly the Cockcroft-Gault equation (80.7%). Carboplatin doses were capped in most hospitals (91.9%): 54.8% capped creatinine clearance at 125 mL/min, 11.3% capped serum creatinine, and 19.3% capped both creatinine clearance and serum creatinine. Serum creatinine cut-off values ranged from 0.36 mg/dL to 1 mg/dL. The most commonly used body weight was actual body weight for underweight, normal weight, and overweight patients. The use of adjusted ideal body weight increased in obese and especially in morbidly obese patients. CONCLUSION: The results from this survey show the variability that exists in carboplatin dose calculation methods among Spanish hospitals and the need to continue investigating to find the optimum dose calculation method and unify criteria to avoid differences between sites that can affect effectiveness and toxicity of carboplatin-containing treatments.

Voriconazole in fungal keratitis caused by Scedosporium apiospermum.

OBJECTIVE: To describe the first case, to the best of our knowledge, of posttraumatic Scedosporium apiospermum (ScA) keratitis successfully treated with systemic and topical voriconazole. CASE SUMMARY: A 19-year-old man was admitted to the hospital with an incisive wound of his left eye and the cornea totally sectioned after trauma with a cutter used in gardening. Initial empirical treatment was followed by systemic and topical voriconazole, and the eye did not have to be enucleated. Five months after the trauma, a penetrating keratoplasty and chamber intraocular lens implantation was performed with a favorable visual outcome. DISCUSSION: ScA keratitis is rare, but it must be suspected if a history of ocular injury with contaminated objects exists. Among the antifungals available to treat ScA keratitis, voriconazole has shown advantages such as the lowest minimum inhibitory concentration and the availability of an oral formulation. CONCLUSIONS: Voriconazole shows promise as an effective alternative to conventional antifungals in the treatment of ScA keratitis. It is available both as oral and intravenous preparations, which is a great advantage in these lengthy infections.