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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.

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.

Abstract For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20–30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Introduction and objectivesCorticosteroids are among the drugs demonstrating a mortality benefit for coronavirus disease 2019 (COVID-19). The RECOVERY trial highlighted that dexamethasone reduced 28-day mortality for hospitalized COVID-19 patients requiring either supplemental oxygen or mechanical ventilation. It is noted that approximately 30% of COVID-19 patients, initially presenting with mild symptoms, will advance to acute respiratory distress syndrome (ARDS), especially those with detectable laboratory markers of inflammation indicative of disease progression. Our research aimed to explore the efficacy of dexamethasone in preventing the progression to ARDS in patients hospitalized with COVID-19 pneumonia who do not yet require additional oxygen but are at high risk of developing ARDS, potentially leading to a reduction in morbimortality.MethodsIn this multicenter, randomized, controlled trial, we evaluated the impact of dexamethasone on adult patients diagnosed with COVID-19 pneumonia who did not need supplementary oxygen at admission but were identified as having risk factors for ARDS. The risk of ARDS was determined based on specific criteria: elevated lactate dehydrogenase levels over 245 U/L, C-reactive protein levels exceeding 100 mg/L, and a lymphocyte count below 0.80 × 109/L. Participants were randomly allocated to either receive dexamethasone or the standard care. The primary endpoints included the incidence of moderate or severe ARDS and all-cause mortality within 30 days post-enrollment.ResultsOne hundred twenty-six patients were randomized. Among them, 41 were female (30.8%), with a mean age of 48.8 ± 14.4 years. Ten patients in the dexamethasone group (17.2%) and ten patients in the control group (14.7%) developed moderate ARDS with no significant differences. Mechanical ventilation was required in six patients (4.7%), with four in the treatment group and two in the control group. There were no deaths during hospitalization or during follow-up. An intermediate analysis for futility showed some differences between the control and treatment groups (Z = 0.0284). However, these findings were within the margins close to the region where the null hypothesis would not be rejected.ConclusionIn patients with COVID-19 pneumonia without oxygen needs but at risk of progressing to severe disease, early dexamethasone administration did not lead to a decrease in ARDS development.Clinical trial registrationClinicalTrials.gov, identifier NCT04836780.

Abstract 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.

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.

Abstract 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.

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.

Abstract Background Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. Methods/design This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of