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Background and ImportanceWe studied the physicochemical and microbiological stability of two methadone oral solutions 10 mg/mL. We demonstrated they were stable at 5 ± 3°C, 25 ± 2°C, and 40 ± 2°C for 91 days so that we increased the beyond-use-date (BUD) from 30 to 91 days.Aim and ObjectivesDescribe and analyse the impact after increasing the methadone solution BUD as well as the overall satisfaction in the-Methadone-Maintenance-Programme (MMP) Drug-Addicts-Attention-Centres (CAID) in our city, in which methadone compounding, distribution and dispensing is centralised in our Hospital-Pharmacy-Department.Material and MethodsOne year after this implementation, a survey (8 questions) was designed with 6 possible Likert-scale answers (value 0 = ‘no-improvement’ and 5 = ‘very-significant-improvement’) asking if the BUD increase had allowed improvements in:Day-to-day organisation.Vacation organisation.Human Resources (HR) distribution.Dosing/dispensing methadone time reduction.Other benefits not included in the survey.Patient visits to the centre reduction (yes/no).Other benefits in dispensing (yes/no).Overall satisfaction (value 1 = ‘not-at-all-satisfied’ and 5 = ‘very-satisfied’).The first 7 questions also included a free field to justify their score.ResultsThe response rate was 90% (18/20). Globally, the BUD increase has led an improvement in 61.1% CAID, highlighting better organisation, management and forecasting/internal planning (orders, shifts, vacations, doctor-nurse activities), as well as the possibility of dispensing more doses. During vacation/festive periods, 66.7% have noticed an improvement (being important/very-important in 38.9%), allowing better planning and dosing in advance. Regarding the HR distribution, the new BUD has not meant an improvement, or it has been of little importance in 94.6%. The reduction of dosing/dispensing time, has obtained a significant/very-significant improvement in 16.6%. In 22.2% CAID, it has allowed to reduce the number of visits to the centre. 27.8% found other important benefits for patients: adequacy of dispensing to their needs (travel, quarantine, vacations). 11.1% CAID indicated other benefits not included in the survey, highlighting the peace of mind due to the scientific certainty of the new BUD, as well as the possibility of ordering more methadone solution. The overall satisfaction was high: 55.6% very-satisfied/fairly-satisfied and the rest indifferent.Conclusion and RelevanceThe increased stability of methadone oral solution has meant a high satisfaction degree in the MMP’s CAID, highlighting an improvement in the daily organisation and in festive periods; in relation to better planning/forecasting of shifts and internal activities; as well as a greater doses dispensing to patients whose clinical situation allowed it, reducing the number of visits to the centre.References and/or AcknowledgementsConflict of InterestNo conflict of interest

Background and importanceIn the absence of evidence about the incidence of bacterial co-infection, antibiotic treatment was widely prescribed to prevent this potential complication. Increasing antibiotic consumption could have exerted an ecological pressure on microorganisms with potential clinical implications that need to be examined.Aim and objectivesThe aim of this study was to analyse antibiotic consumption and antimicrobial resistant microorganism isolates during the peak incidence of the COVID-19 first wave at our hospital.Material and methodsAn observational, descriptive, cross sectional study was carried out. Antibiotic consumption data for March and April 2020 and 2019 were analysed. Defined daily dose (DDD) per 100 bed days was used as the consumption indicator and changes were expressed in absolute and percentage terms. Isolates of Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae) were examined for March and April 2020 and compared with the average over 2019. Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae were expressed in relative terms over their total isolates.ResultsFor the period under study, antibiotic consumption increased from 79.94 to 141.10 DDD/100 bed days in 2020, which was an increase of 77%. Macrolides and cephalosporins were among the groups of antibiotics with the highest consumption, representing 37% (52.79 DDD/100 bed days) and 32% (45.41 DDD/100 bed days) of total consumption, respectively, and almost 70% jointly. Additionally, ceftriaxone and azithromycin showed an increase in DDD/100 bed days of 4.5× (8.91 vs 39.97) and 27.4× (1.89 vs 51.90) with respect to the same period in 2019.The share of ESBL producing Escherichia coli was 12% (13/111 isolates) and 23% (20/87 isolates) in March and April 2020 compared with an average of 11% (273/2494 isolates) in 2019. ESBL producing Klebsiella pneumoniae was 23% (8/35 isolates) and 57% (25/44 isolates) in March and April 2020 versus 24% (153/642 isolates) on average in 2019.Conclusion and relevanceDuring the study period, antibiotic consumption increased markedly. The increasing use of third generation cephalosporins, which have no effect on ESBL producing Enterobacteriaceae, may have contributed to the observed changes in the bacterial ecology in our hospital. As the incidence of bacterial co-infection on admission was reported to be lower than 5% and the increase in antibiotic consumption translated into selection of antibiotic resistant bacteria, it is important to properly assess antibiotic treatment for each particular case in future outbreaks of SARS-CoV-2 infections.References and/or acknowledgementsConflict of interestNo conflict of interest

Background and importanceOver the past 10 years, a pharmacotherapy revolution in the treatment of moderate to severe plaque psoriasis (MS-PP) has occurred. In our country, the prescription of ustekinumab has increased greatly since its approval in 2009. Therefore, it is now time to reflect on its use and to assess the real world setting, before the arrival of newly approved drugs.Aim and objectivesThe primary end point was to assess drug survival for ustekinumab for MS-PP treatment. The secondary end point was to assess the effectiveness of ustekinumab for MS-PP treatment.Material and methodsA retrospective observational study was conducted. All patients who had started treatment with ustekinumab for MS-PP from January 2009 to December 2017 were included. Data collected were demographics, line of biological treatment, dates for therapy start and discontinuation, reason for discontinuation, intensification, optimisation, and psoriasis area severity index (PASI) before starting ustekinumab and at weeks 24, 52 and at the last evaluation available.Drug survival was analysed using Kaplan–Meier plots and effectiveness was evaluated by PASI50, 75, 90 and 100. Subsequently, data were analysed with SPSS21.ResultsA total of 130 patients were included, 64.6% men, with a mean age of 44.4 (11–83) years. Treatment line of ustekinumab: firstline 65.4%, secondline 23.1%, third and subsequent lines, 11.5%. Intensification and optimisation was performed in 59.2% and 53.1%, respectively. Mean drug survival was 6.7 years (95% CI 6.06–7.42).Effectiveness was calculated for 101 patients because of lack of data. Mean PASI at the start was 11.3 (SD 6.8). At week 24, the relation of PASI 50/75/90/100 achieved was 74.3%/67.3%/56.4%/45.5%, respectively (no data available for 11patients). At week 52, the relation of PASI 50/75/90/100 achieved was 90.0%/75.0%/62.5%/51.3%, respectively (no data available for 21patients). At the end of the study, 84 patients continued treatment with ustekinumab and their mean PASI at that time was 1.2 (SD 2.3). Reasons for discontinuation were drug failure in 20.8%, no reason described in 7.7%, improvement in 3.1%, neoplasms in 2.3%, intolerance in 0.8% and patient preference in 0.8%.Conclusion and relevanceThe PHOENIX trials opened the window to PASI90 and we have confirmed the effectiveness of ustekinumab in real life. Furthermore, the results reported here indicated that this effectiveness persisted for a long time, as recently reported data by Salgüero-Fernandez. Therefore, this fact should be an unbiased factor to consider before changing psoriasis therapy to newer drugs based on our long term data.References and/or acknowledgements1. Salgüero-Fernández I, et al. https://doi.org/10.1016/j.ad.2018.02.019No conflict of interest.

Background and importanceAfter the National Institute for Occupational Safety and Health (NIOSH) classified hazardous drugs (HD), it was deemed necessary to make healthcare workers aware of the risks associated with handling HD in their daily work to mitigate these risks.Aim and objectivesTo analyse oral HD handling activities to make handling recommendations based on the lowest dust inhalation risk and to ensure the safety of healthcare workers in hospital units.Material and methodsOral HD were classified into two categories: groups 1 and 2 and group 3 according to NIOSH grouping system. Secondly, oral HD handling activities in hospital units based on their dust inhalation risk to the workers were ranked and decisions were taken accordingly: opening capsules and sachets must be avoided; marketed liquid formulations is strongly preferred; and in their absence, crushing tablets using closed systems is preferred over compounding medications due to shorter administering periods in hospital units. Finally, the above mentioned ranking was followed for every oral HD. If no marketed liquid alternatives were found, research on techniques for crushing and dissolving tablets was conducted. In the absence of crushing techniques, academic research on compounding oral HD was carried out. For the remaining oral HD, information was requested from the manufacturers.ResultsA total of 59 active pharmaceutical ingredients (API) from groups 1 and 2 were analysed. Marketed liquid formulations were found for 13 API (abacavir, ciclosporin, crizotinib, phenytoin, megestrol, mycophenolate mofetil, mycophenolic acid, nevirapine, oxcarbazepine, trametinib, tofacitinib, valganciclovir, and zidovudine). Techniques on crushing and dissolving tablets were available for 21 API (abiraterone, axitinib, busulfan, dasatinib, entecavir, enzalutamide, everolimus, exemestane, flutamide, imatinib, letrozole, medroxyprogesterone, melphalan, mercaptopurine, methimazole, methotrexate, mitotane, ponatinib, rasagiline, sorafenib and tamoxifen).For 13 API (azathioprine, capecitabine, carbamazepine, cyclophosphamide, chlorambucil, etoposide, hydroxyurea, procarbazine, spironolactone, sunitinib, tacrolimus, thalidomide and topotecan) compounding oral information was found. No information was obtained for 12 API (20.3%) (bexarotene, bosutinib, cabozantinib, fingolimod, fludarabine, ixazomib, lenalidomide, nilotinib, pazopanib, pomalidomide, regorafenib and vinorelbine) for which avoiding their handling and seeking other therapeutic alternative was advised. For the remaining 79.7% of API, priority was given to the recommendation of the lowest dust inhalation risk handling alternative.Conclusion and relevanceSafe handling alternatives were found for most of the analysed oral HD in the sample, with potential to minimise workers’ handling risk and ensure safety measures in hospital units.References and/or acknowledgementsNo conflict of interest.

Background and importanceOn the basis of resolution 189/2018 published by our city health council, the hospital pharmacy service was entrusted with the centralisation of the procedure for the acquisition, compounding, distribution and dispensing of methadone to drug addicts in integral attention centres. In order to improve and increase the beyond use date (BUD) of methadone oral solutions, we carried out a physicochemical stability study.Aim and objectivesTo develop an analytical method and validation to carry out a physicochemical stability study of two oral solutions of methadone to increase their BUD. Method development should be made in an effective and reproducible manner.Material and methodsThe study was carried out on two formulations of methadone 10 mg/mL, which were prepared with and without parabens as preservatives. A high performance liquid chromatography (HPLC) Agilent 1100 was used, provided with a quaternary pump and an ultraviolet diode array detector to determine methadone. First we carried out the analytical method development to achieve the analytical performance characteristics. Then we performed validation of the analytical method obtaining linearity, instrumental intra-assay and inter-assay precision, and accuracy and recovery percentage.ResultsChromatographic conditions were: flow rate 1.6 mL/min, 55% acetonitrile and 45% phosphate buffer (adjusted to pH=10) as the mobile phase. Injection volume was 50 µL, the temperature in the column compartment was 40°C. The column used was the Xterra C18 because methadone pKa is 8.3. Retention time for methadone was 4.5 min and for parabens 1.5 min.The final methadone determination method was validated for a standard of 10 mg/mL and applied for the determination of methadone with two parabens. The most relevant results were: correlation coefficient r=0.9957 for methadone in the range tested (7.5–12.5 mg/mL); instrumental precision 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%, and the percentage recovery was 101.5 ±1.5%.Conclusion and relevanceAnalytical method development and validation procedures are vital in the discovery and development of drugs and pharmaceuticals to ensure performance of the method. The proposed HPLC conditions to determine methadone were proved to be valid and reproducible for carrying out physicochemical stability studies of different methadone oral solutions.References and/or acknowledgementsNo conflict of interest.

BackgroundThe National Institute for Occupational Safety and Health (NIOSH) has studied only the hazards of marketed drugs, excluding raw materials (RM). For this reason, it is necessary to study the hazards of RM used in the compounding of pharmaceuticals formulations.PurposeAnalyse and establish the hazards of RM used in our pharmacy department. Also, classify the type of health hazards of RM in order to establish protective measures (PM) when handling them.Material and methodsDescriptive study carried out in June to September 2018. All safety data sheets (SDS) of RM (provided by Fagron) used in our hospital were reviewed. Regulation No 1272/2008 of the Classification, Labelling and Packaging of substances and mixtures (CLP) establishes a system for identifying chemical risk. Health hazards are found in the range H300–H373. We subdivided RM with health hazards into four groups depending on toxicity properties: Group 1 (G1): carcinogenic (H350–H351); Group 2 (G2): mutagenic/teratogenic (H340–H341); Group 3 (G3): reproduction/breastfeeding toxicity (H360–H361); and Group 4 (G4): others (ocular, cutaneous, gastrointestinal or respiratory toxicity). Finally, we established PM to prevent hazards when handling RM.ResultsEighty-one RM were analysed. Thirty-three (40.7%) were not classified according to CLP regulations, so they were excluded. Twenty-three RM (28.4%) had no health hazards. Finally, 25 RM (30.9%) were found with any health hazards, of which 13 belonged to any of the groups G1–G3. G1: six RM (7.4%): atenolol, budesonide, diltiazem, spironolactone, phenobarbital and furosemide; G2: one RM (1.2%): phenol; and G3: seven RM (8.6%): boric acid, dexamethasone, disodium tetraborate, triamcinolone acetonide, clobetasol, captoril and phenobarbital. The other 12 RM were in G4. Regarding PM, we established the use of Biological Safety Cabinet Class I to handle G1–G3 RM and the use of personal protective equipment including gloves, protective gown and respiratory protection. It is worth stressing that marketed drugs containing the following active pharmaceutical ingredients analysed atenolol, budesonide, diltiazem, phenobarbital, furosemide, dexamethasone, triamcinolone acetonide, clobetasol and captoril are not included in the NIOSH list.ConclusionApproximately one-third of RM analysed have any health hazards. It is necessary to review the hazards of RM used in pharmacy departments to prevent workers’ occupational exposure. Despite CLP regulation, there are plenty of RM that remain unclassified. Further studies related to harzardous RM are necessary.References and/or acknowledgementshttps://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A32008R1272https://www.cdc.gov/niosh/docs/2016–161/pdfs/2016–161.pdfNo conflict of interest.

Background Dupuytren’s disease leads to progressive finger contractures, limiting hand function. Traditional treatment consists of open partial fasciectomy, which requires hospitalisation, anaesthesia and physiotherapy. Recent introduction of Clostridium hystoliticum collagenase into treatment has minimised the economic impact. Purpose To evaluate the efficacy, safety and financial impact of collagenase versus fasciectomy after its introduction in the hospital. Materials and methods A retrospective observational study was performed in a 400-bed university hospital. All patients treated with collagenase since May 2012 were enrolled in the study. Data were collected from medical histories to study efficacy and safety: sex, age, concomitant disease, pharmacotherapeutic history, previous operations and adverse events. We considered treatment was effective when residual contracture was <5º after 4 weeks of collagenase injection. Costs of surgery and consultation were obtained from the GECLIF (Financial Clinical Management) application. The cost of collagenase was calculated based on the average price of its acquisition by the pharmacy. The average cost of fasciectomy includes costs of surgery, hospital stay and associated consultations. Average cost of treatment with collagenase includes the cost of the drug and associated consultations. We compared average costs between the two treatments using the T-Student-Fisher Test. Confidence intervals were calculated for a confidence level of 95% (CI95%) and p values ≤0.05 were considered statistically significant. Results Nine subjects (7 men and 2 women) with an average age of 68 years (range 62–76), diagnosed with Dupuytren’s contracture with palpable cord were enrolled in the study. 55.6% had relapsed after previous surgery. Injectable collagenase was administrated according to Product Information sheet into the metacarpophalangeal joints (66.7% of patients) or interphalangeal joints (33.3% of patients). Residual contracture <5º was achieved in 88.9% (n = 8) of patients. None experienced relapse. One was recently treated, so we have no efficacy results. Mild to moderate adverse events were reported in 88.9% of patients that resolved with appropriate treatment. These included peripheral oedema and hematoma (77.8%), skin lacerations at injection site (44.4%), paresthesia and pain (11.1%), scab, erythema or pruritus (33.3%). Average cost per patient for fasciectomy was 1,503 € and for treatment with collagenase was 923 €. Collagenase treatment cost an average 580 € (509.51–651.06 €, CI95%; p < 0.001) less per patient than fasciectomy. Conclusions Treatment for Dupuytren’s contracture with collagenase is effective and well tolerated in most of patients. It represents a decrease of 38.6% in costs to hospital versus the average cost of fasciectomy per patient. No conflict of interest.

Background and importanceHospital at home (HaH) units provide hospital level care at home to patients who would otherwise remain hospitalised. This hospitalisation model is growing as it saves costs, reducing hospital stay and complications such as nosocomial infections. Antibiotic stewardship programmes demonstrated success in conventional hospitalisation, and these interventions might be extended to HaH units. At the beginning of 2019, the antibiotic stewardship programme (ASP) made two interventions in the HaH unit: to prescribe fluoroquinolones only to patients with no safer alternatives based on the restriction made by the Spanish Agency of Medicines and Medical Devices (AEMPS) in 2018, and the advice to reduce the prescribed dose of cefixime from 400 mg/12 hours to 400 mg/24 hours.Aim and objectivesThe aim of the present study was to analyse the influence of the ASP interventions in a HaH unit.Material and methodsAn observational, descriptive, cross-sectional study was carried out. Antibiotic consumption data from January 2017 to December 2019 were analysed. Defined daily dose (DDD) per 100 bed days was used as the indicator to measure antibiotic consumption, and increases or decreases in consumption were expressed in absolute terms. Data analysis was carried out using Microsoft Excel 2013.ResultsGlobal antibiotic consumption was reduced progressively since 2018: 133.85 DDD/100 bed days (2017); 127.02 DDD/100 bed days (2018) and 101.95 DDD/100 bed days (2019). Fluoroquinolone consumption was 26.18 DDD/100 bed days in 2017. Since the recommendation made by the AEMPS, a more rationale use was observed in 2018 (21.62 DDD/100 bed days). After the ASP recommendations, its consumption fell to 15.16 DDD/100 bed days in 2019 (14.40% reduction 2018–2019). Cefixime consumption was 17.74 DDD/100 bed days in 2017 and increased to 20.62 DDD/100 bed days in 2018. After the ASP intervention, it was reduced to 11.12 DDD/100 bed days in 2019 (7.13% reduction 2018–2019).Conclusion and relevanceAntibiotic stewardship programme interventions were effective in reducing antibiotic consumption in the HaH unit. Prescription restrictions related to fluoroquinolones due to their safety profile and cefixime dosing intervention were effective and reflected a reduction in consumption. HaH units could potentially benefit from the positive effects of antibiotic stewardship teams as conventional hospitalisation units.References and/or acknowledgementsConflict of interestNo conflict of interest

BackgroundPenicillin G 20 MIU/day for 4–6 weeks followed by oral amoxicillin for 6–12 months is the first option of treatment for abdominal actinomycosis where other therapies have less effectiveness.PurposeTo describe a desensitisation protocol for Penicillin G in a patient with abdominal actynomicosis that had experienced a severe anaphylactic reaction (tachycardia, redness, bronchospasm and refractory hypotension) to ceftriaxone that required a perfusion of noradrenalina, in addition to adrenaline, corticosteroids and salbutamol for recovering.Material and methodsPenicillin G vials were reconstituted with water for injection as indicated on its label and they were diluted with 0.9% sodium chloride to make four mother solutions (0.1 mg/ml, 1 mg/ml, 10 mg/ml and 100 mg/ml of β-lactamic). Doses were prepared in syringes. Initial dose was 16 IU, with subsequent syringes elaborated doubling the dose until a cumulative dose of 5 MIU. A total of 19 syringes were prepared in a horizontal laminar flow cabinet in the pharmacy service: dilution 0.1 mg/ml (160 IU/ml): 16 IU/0.1 ml, 32 IU/0.2 ml, 64 IU/0.4 ml and 128 IU/0.8 ml. Dilution 1 mg/ml (1,600 IU/ml): 240 IU/0.15 ml, 480 IU/0.3 ml, 960 IU/0.6 ml and 1,600 IU/1 ml. Dilution 10 mg/ml (16,000 IU/ml): 3,200 IU/0.2 ml, 6,400 IU/0.4 ml and 12,800 IU/0.8 ml. Dilution 100 mg/ml (160,000 IU/ml): 24,000 IU/0.15 ml, 48,000 IU/0.3 ml, 96,000 IU/0.6 ml, 16,000 IU/1 ml, 320,000 IU/2 ml, 640,000 IU/4 ml, 1,280,000 IU/8 ml and 2,400,000 IU/15 ml.ResultsDue to the high risk of the patient, despite negative allergological tests, a desensitisation protocol was administrated by allergists in the intensive care unit with monitoring and cardiopulmonary resuscitation equipment. The time interval between each syringe was 10 min in direct bolus, the last three doses were administered during 10–15 min due to the higher doses and infusion pain. The schedule was achieved without any reaction. After this, a whole dose of 5 MUI/6 hours was administered during 2 months without any adverse reaction.ConclusionThis desensitisation protocol can be useful for penicillin-allergic patients without alternative treatment options.References and/or acknowledgementsDávila González IJ, Sociedad Española de Alergología e Inmunología Clínica. Tratado de alergología. 2nd Ed. Vol. 2. Majadahonda: Ergón; 2016.No conflict of interest.