Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases.

Niemann-Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-ß-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-ß-CD was 14 years (range 2-49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-ß-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-ß-CD in NP-C.

[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.

[Translated article] Analysis of the degree of implementation of medication error prevention practices in Spanish hospitals (2022).

OBJECTIVE: To assess the degree of implementation of medication error prevention practices in Spanish hospitals. METHOD: Descriptive multicenter study of the degree of implementation of the safety practices included in the "Medication use-system safety self-assessment for hospitals. Version. II". Spanish hospitals that completed the questionnaire between October, 2021 and September, 2022 participated. The survey contains 265 items for evaluation grouped into 10 key elements. Mean score and mean percentages based on the maximum possible values for the overall survey, for the key elements, and for each individual item of evaluation were calculated. The results were compared with those of the previous 2011 study. RESULTS: A total of 131 hospitals from 15 autonomous regions participated in the study. The mean score of the overall questionnaire in all hospitals was 898.2 (57.4% of the maximum possible score). No differences were found according to dependency, size, or type of hospital, either in the overall questionnaire or in the key elements. The lowest values were found for key elements VIII, I and VI, on competence and training of health professionals in safety practices (45.1%), availability and accessibility of essential information on patients (48%), and devices for administering drugs (52.3%). With respect to 2011, significant increases were found both in the overall questionnaire and in the key elements, except V and VII, referring to standardization, storage, and distribution of medications, and environmental factors and human resources. Several evaluation items on the safe management of high-risk drugs, medication reconciliation, incorporation of clinical pharmacists into the healthcare teams, and implementation of technologies that allow full traceability throughout the medication system, showed low percentages. CONCLUSIONS: There has been appreciable progress in the degree of implementation of some medication error prevention practices in Spanish hospitals, but many proven efficacy practices recommended by the World Health Organization and safety organizations are still poorly implemented. The information obtained can be useful for prioritizing the practices to be addressed and as a new baseline for monitoring progress.

Analysis of the degree of implementation of medication error prevention practices in Spanish hospitals (2022). / Análisis del grado de implantación de las prácticas de prevención de errores de medicación en los hospitales españoles (2022).

OBJECTIVE: To assess the degree of implementation of medication error prevention practices in Spanish hospitals. METHOD: Descriptive multicenter study of the degree of implementation of the safety practices included in the "Medication use-system safety self-assessment for hospitals. Version. II". Spanish hospitals that completed the questionnaire between October/2021 and September/2022 participated. The survey contains 265 items for evaluation grouped into 10 key elements. Mean score and mean percentages based on the maximum possible values for the overall survey, for the key elements and for each individual item of evaluation were calculated. The results were compared with those of the previous 2011 study. RESULTS: A total of 131 hospitals from 15 autonomous regions participated in the study. The mean score of the overall questionnaire in all hospitals was 898.2 (57.4% of the maximum possible score). No differences were found according to dependency, size or type of hospital, either in the overall questionnaire or in the key elements. The lowest values were found for key elements 8, 1 and 6, on competence and training of health professionals in safety practices (45.1%), availability and accessibility of essential information on patients (48%), and devices for administering drugs (52.3%). With respect to 2011, significant increases were found both in the overall questionnaire and in the key elements, except 5 and 7, referring to standardization, storage and distribution of medications, and environmental factors and human resources. Several evaluation items on the safe management of high-risk drugs, medication reconciliation, incorporation of clinical pharmacists into the healthcare teams and implementation of technologies that allow full traceability throughout the medication system, showed low percentages CONCLUSIONS: There has been appreciable progress in the degree of implementation of some medication error prevention practices in Spanish hospitals, but many proven efficacy practices recommended by the World Health Organization and safety organizations are still poorly implemented. The information obtained can be useful for prioritizing the practices to be addressed and as a new baseline for monitoring progress.

Monitoring the quality of the hospital pharmacoterapeutic process by sentinel patient program.

OBJECTIVE: To analyze the results of sentinel patient program to monitoring the  quality pharmacoterapeutic process in the hospitalized patient through  medication errors. METHOD: Design: Observational, prospective and transversal study. Ambit: General hospital of 1,000 beds. PERIOD: From May 2011 to June 2016.  Sample: Patients with treatment prescribe within 24 hours of being admitted  with 4 or more medications. VARIABLES: Medication error, drugs prescribed,  medications and doses dispensing, drugs administered. Safety indicators were  defined based on medication errors at each stage of the pharmacotherapeutic  process. RESULTS: Of the 746 patients studied, 334 had at least 1 medication error  (44.8%; IC95%: 41.7-47.8). In the 746 treatments, 564 medication errors were  detected (0.75 errors by patient; IC95%: 0.7-0.8). The safety indicators  (medication error by stage) were: 5.1% (38/746 patients) for omission of  allergy record; 2.3% (156/6 724 drugs) for prescription; 0.6% (38/6 724 drugs)  for validation, 2.6% for dispensing (142/5 465 drugs) y 3.7% (190/5  111 administered drugs observed) for administration. The temporal evolution of  the indicators, with graphs of statistical control showed stable processes, except  for the administration. The proposed improvement actions were of a training,  standardization and organizational type. CONCLUSIONS: The sentinel patient program provides an overview of the quality  of the pharmacotherapeutic process and promotes the safety culture at the  center. Statistical control charts have been a useful tool for monitoring  medication errors. The analysis of medication errors has served to propose  improvement actions in each stage of the pharmacotherapeutic process.

Objetivo: Analizar los resultados del programa paciente centinela para la monitorización de la calidad del proceso farmacoterapéutico en el paciente hospitalizado mediante indicadores basados en errores de medicación.Método: Diseño: Estudio observacional, transversal y prospectivo. Ámbito: Hospital general de 1.000 camas. Periodo: mayo 2011-junio 2016. Muestra: Pacientes con cuatro o más medicamentos. VARIABLES: Error de medicación, medicamentos prescritos, medicamentos y dosis preparadas, medicamentos administrados. Se definieron indicadores de  seguridad a partir de los errores de medicación en cada fase del proceso farmacoterapéutico.Resultados: Durante el periodo de estudio, 334 de 746 pacientes presentaron algún error, lo que supuso un 44,8% (IC95%: 41,7 a 47,8). Se detectaron 564 errores de medicación (0,75 errores por paciente; IC95%: 0,7 a 0,8). Los indicadores de seguridad (errores de medicación por  fase): omisión de registro de alergia 5,1% (38/746 pacientes); prescripción  2,3% (156/6.724 medicamentos); validación 0,6% (38/6.724 medicamentos), preparación: 2,6% (142/5.465 medicamentos) y  administración: 3,7% (190/5.111 administraciones observadas). La evolución  temporal de los indicadores, con gráficos de control estadístico, mostró procesos  estables, excepto para la fase de administración. Las acciones de  mejora propuestas fueron de normalización, formación y organización.Conclusiones: El programa paciente centinela proporciona una visión global de  la calidad del proceso farmacoterapéutico y fomenta la cultura de seguridad en  el centro. Los gráficos de control estadístico han sido una herramienta útil para  monitorizar los errores de medicación. El análisis de los errores de medicación  ha servido para plantear acciones de mejora en cada una de las fases del  proceso farmacoterapéutico.