Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients.

It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence.

Design of mobile and website health application devices for drug tolerability in hereditary fructose intolerance.

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. RESULTS: A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. CONCLUSIONS: IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.

[Translated article] Deglufarm: Mobile application with recommendations for the safe administration of drugs in patients with dysphagia or swallowing disorders.

OBJECTIVE: Develop an App to use in healthcare practice, with updated and accurate information on the handling of medications in patients with dysphagia or deglution disorders, as well as their compatibility with food and thickeners. METHODS: The development of the Deglufarm® App was based on the CRONOS, Nutrition and Techno working groups of the Sociedad Española de Farmacia Hospitalaria. A group of specialist pharmacists was created from different care areas for patients with dysphagia. The creation of Deglufarm® consisted of several stages: selection of active drugs, literature review, content development, design (an expert company in App design was contacted), testing, launch, content update and follow-up. RESULTS: Deglufarm® is available for Android and IOS free of charge from July 2022. It has been tested among the members of the research group and collaborators, Currently, 540 monographs of active drugs have been reviewed and registered in Deglufarm. The first version is aimed at healthcare professionals. CONCLUSIONS: Deglufarm® is an easy tool to consult, with the most current evidence on handling the medicines it contains.

Deglufarm: Mobile application with recommendations for safety drug administration in patients with dysphagia or deglution disorders. / Deglufarm: aplicación móvil con recomendaciones para la administración segura de medicamentos en pacientes con disfagia o problemas de deglución.

OBJECTIVE: Develop an App to use in healthcare practice, with updated and accurate information on the handling of medications in patients with dysphagia or deglution disorders, as well as their compatibility with food and thickeners. METHODS: The development of the Deglufarm® App was based on the CRONOS, Nutrition and Techno working groups of the Sociedad Española de Farmacia Hospitalaria. A group of specialist pharmacists was created from different care areas for patients with dysphagia. The creation of Deglufarm® consisted of several stages: Selection of active drugs, literature review, content development, design (an expert company in App design was contacted), testing, launch, content update and follow-up. RESULTS: Deglufarm® is available for Android and IOS free of charge from July 2022. It has been tested among the members of the research group and collaborators, currently, 540 monographs of active drugs have been reviewed and registered in Deglufarm. The first version is aimed at healthcare professionals. CONCLUSIONS: Deglufarm® is an easy tool to consult, with the most current evidence on handling the medicines it contains.

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL.

In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies.

PURPOSE: The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3000 L of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date. METHODS: A HPLC-Agilent® 1100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75-125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed. RESULTS: Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH = 10); injection volume was 5 µL. The column was a Waters-XTerra™ RP18, maintained at 40 °C. DAD was λ = 254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 min respectively. The method was linear (y = 284.3x - 97.8, r = 0.996). Instrumental precision was 0.33% for standards (n = 10); intra-assay precision 0.53% (n = 6) and inter-assay precision 1.95% (n = 12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 µg/mL and 2.0 µg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal. CONCLUSIONS: The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.

Reply letter to the editor concerning the article 'Safety of Sars-Cov-2 vaccines administration for adult patients with hereditary fructose intolerance'.

According to the current European medicines legislation, on the labeling is mandatory a warning contraindicating for hereditary fructose intolerance (HFI) patients medicines with oral or parenteral fructose and sorbitol, and oral sucrose, invert sugar, isomaltitol, lactitol and maltitol, but parenteral sucrose is not mentioned. Intravenous administration of sucrose does not increase blood glucose concentrations, because sucrose is poorly oxidized to CO2 and mainly excreted in the urine as a disaccharide; absence of enzimatic activity outside the gut explains why there is not a warning for parenteral sucrose presentations. For this reason, parenteral drugs with sucrose are allowed in HFI patients. Nevertheless, due to interindividual variability and the fact that not all parenterally administered sucrose is recovered in urine, HFI patients need to be closely monitored after parenteral administration of sucrose-containing drugs, especially when the amount exceeds the maximum permissible thresholds.

Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study.

OBJECTIVES: To describe demographic, clinical, radiological and laboratory characteristics, as well as outcomes, of patients admitted for COVID-19 in a secondary hospital. DESIGN AND SETTING: Retrospective case series of sequentially hospitalised patients with confirmed SARS-CoV-2, at Infanta Leonor University Hospital (ILUH) in Madrid, Spain. PARTICIPANTS: All patients attended at ILUH testing positive to reverse transcriptase-PCR on nasopharyngeal swabs and diagnosed with COVID-19 between 1 March 2020 and 28 May 2020. RESULTS: A total of 1549 COVID-19 cases were included (median age 69 years (IQR 55.0-81.0), 57.5% men). 78.2% had at least one underlying comorbidity, the most frequent was hypertension (55.8%). Most frequent symptoms at presentation were fever (75.3%), cough (65.7%) and dyspnoea (58.1%). 81 (5.8%) patients were admitted to the intensive care unit (ICU) (median age 62 years (IQR 51-71); 74.1% men; median length of stay 9 days (IQR 5-19)) 82.7% of them needed invasive ventilation support. 1393 patients had an outcome at the end of the study period (case fatality ratio: 21.2% (296/1393)). The independent factors associated with fatality (OR; 95% CI): age (1.07; 1.06 to 1.09), male sex (2.86; 1.85 to 4.50), neurological disease (1.93; 1.19 to 3.13), chronic kidney disease (2.83; 1.40 to 5.71) and neoplasia (4.29; 2.40 to 7.67). The percentage of hospital beds occupied with COVID-19 almost doubled (702/361), with the number of patients in ICU quadrupling its capacity (32/8). Median length of stay was 9 days (IQR 6-14). CONCLUSIONS: This study provides clinical characteristics, complications and outcomes of patients with COVID-19 admitted to a European secondary hospital. Fatal outcomes were similar to those reported by hospitals with a higher level of complexity.

Centralization of the methadone maintenance plan in a hospital pharmacy department in the Community of Madrid.

In February 2018, Resolution 189/2018 was published in the Autonomous Community of Madrid with the objective of centralizing the  procedure for the acquisition, preparation, distribution, and dispensing of methadone to Centres for the Comprehensive Care of Drug Addiction Patients  within the Madrid Health Service under the responsibility of a Hospital Pharmacy  Service. The Hospital Pharmacy Service began this activity in March 2018. This is the first time that the comprehensive management of a methadone  maintenance plan has been centralized in an Hospital Pharmacy Service for the care of drug-dependent patients in the Autonomous Community of Madrid. At the beginning of the Project, the previous workflow was analysed, the pharmaceutical laboratory was adapted, and the methadone acquisition procedure was designed. A communication channel with the Centres  for the Comprehensive Care of Drug Addiction Patients was implemented and application forms were designed. Corresponding control procedures were established given that the medication under consideration was a narcotic. Standard procedures for the acquisition of methadone, of containers for personalized dosing in Centres for the Comprehensive Care of Drug Addiction  Patients, and transport routes were designed and contracted out through public  tender in compliance with the Public Administration Contract Law. A tender has  also been awarded for the implementation of a computerized management  system and automated dispensing systems, which are currently undergoing  installation. The pharmacotherapeutic protocol of the Methadone Maintenance Plan of the Autonomous Community of Madrid is also being updated. Over 18  months, 5,300 L of methadone solution have been prepared and 2,844 individual prescriptions have been dispensed. High levels of perceived satisfaction were  reported via a questionnaire administered to the Centre for the Comprehensive  Care of Drug Addiction Patients staff. The response rate was 92%. Overall  satisfaction was very satisfied/quite satisfied (91%) and satisfied (9%). These  results highlight the high level of satisfaction (quite satisfied or very satisfied:  81.8%) with the effectiveness and speed of resolution of incidents by the  Hospital Pharmacy Service staff. This process incorporates the knowledge and  experience of hospital pharmacists into this healthcare field, as well as taking  advantage of existing resources, facilities, and procedures. All these aspects lead to an efficient, effective, and safe approach to this clinical-care activity and  enable a change in the pharmacotherapeutic health care model for opioid- dependent patients.

En febrero de 2018 se publicó en la Comunidad de Madrid la Resolución 189/2018 con el objetivo de centralizar el procedimiento de  adquisición, elaboración, distribución y dispensación de metadona a los Centros de Atención Integral a Drogodependientes del Servicio Madrileño de Salud bajo la responsabilidad de un servicio de farmacia hospitalaria. El  servicio de farmacia hospitalaria inició esta actividad en marzo de 2018, siendo  la primera vez que se centraliza en un servicio de farmacia hospitalaria la  gestión integral del plan de mantenimiento con metadona para la atención de  pacientes drogodependientes en la Comunidad de Madrid. Al inicio del proyecto  se analizó el circuito anterior, se adaptó el laboratorio de farmacotecnia y se  diseñó el procedimiento de adquisición de metadona. Se implementó una vía de  comunicación con los Centros de Atención Integral a Drogodependientes,  diseñándose formularios de solicitud y se establecieron los correspondientes  procedimientos de control derivados de su naturaleza estupefaciente. Se han  diseñado y adjudicado, cumpliendo la Ley de Contratos de la Administración  Pública, procedimientos normalizados para la adquisición de metadona, envases  para la dosificación personalizada en los Centros de Atención Integral a  Drogodependientes y rutas de transporte. Asimismo, se ha adjudicado un  concurso para la implementación de un sistema informático de gestión y  sistemas automatizados de dispensación, actualmente en vías de instalación. También se está actualizando el protocolo farmacoterapéutico del Plan de  mantenimiento con metadona de la Comunidad de Madrid. En año y medio se  han elaborado 5.300 litros de metadona solución y se han dispensado 2.844  prescripciones individualizadas. Disponemos de resultados de calidad percibida  por los profesionales de los Centros de Atención Integral a Drogodependientes  mediante una encuesta de satisfacción. La tasa de respuesta fue del 92%. El  grado de satisfacción global fue: 91% muy satisfecho/bastante satisfecho y 9%  satisfecho. Destaca el alto grado de satisfacción (bastante o muy satisfecho) del  81,8% con la eficacia y rapidez de la resolución de incidencias por parte de los  profesionales del servicio de farmacia. Este proceso permite incorporar el  conocimiento y experiencia de los farmacéuticos especialistas a este ámbito  asistencial, así como aprovechar recursos, instalaciones y procedimientos ya  existentes. Todo ello redunda en un abordaje eficiente, eficaz y seguro de esta  actividad clínico-asistencial y posibilitar un cambio de modelo de asistencia  farmacoterapéutica de los pacientes dependientes de opiáceos.