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Background Therapeutic drug monitoring (TDM) of infliximab (IFX) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is increasingly used in clinical routine, although proactive TDM is still controversial. Nevertheless, disease activity and drug clearance are higher at the induction phase leading to an increased risk of inadequate drug exposure and treatment failure. The aim of the study was to evaluate the efficacy of the implementation of an early proactive TDM strategy, comparing clinical remission (CR) and biochemical remission (BR) at week 14 and 52, and endoscopic improvement (EI) between two groups. Methods Retrospective cohort study conducted in an Inflammatory Bowel Disease (IBD) unit of a tertiary care hospital. Biologic-naïve patients diagnosed of CD or UC who initiated IFX from 2019 to 2021 (p-TDM group) and from 2016 to 2019 (no-TDM group) were included. In the p-TDM group, proactive IFX trough levels and antidrug antibodies were measured since week 2 and dose adjustment since week 6 was performed using a previously validated population pharmacokinetic model (Fasanmade et al. Clinical Therapeutics 2011). In the no-TDM group, dose escalation was performed considering symptoms, blood, or stool results. CR was defined as Harvey-Bradshaw Index Moreover, surgery, hospitalization and treatment discontinuation rates were compared between both groups. Results 30 patients were included in each group: 13 UC, 16 CD and 1 IBD unclassified. There were no statistical differences in baseline characteristic between groups (table 1). Outcomes at week 14 and 52 are shown in table 2. At week 14, CR rate was significantly higher in p-TDM than in no-TDM (86.7% vs 56.7%, p=0.01). Although BR rate at week 14 was numerically higher in p-TDM, it did not achieve statistical significance (61.1% in p-TDM vs 50.0% in no-TDM, p=0.59). However, limitations in blood and stool collection were considerable at this timepoint. During first year, hospitalizations tend to be fewer in p-TDM group. There were no statistically differences in CR and BR or in EI between groups at week 52. Although OR rate was higher in p-TDM than in no-TDM, it did not reach statistical significance (60.9% vs 33.3%, p=0.06). Conclusion Proactive TDM during induction phase, especially in naïve patients, could be a useful tool to obtain optimal IFX trough levels and to classify correctly primary failure.

Background. The health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment. Methods. Descriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics. Results. A total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordinationorganization (57: 10.7%). Conclusion. The COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (−€193.99 [195.88] vs. −€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. −€10.90 [157.42], p < 0.001) and total costs (€3268.90 [4821.55] vs. −€334.67 (905.44), p < 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.

Introduction Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents. Areas covered This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15th, 2020 and updated on March 30th, 2021. Expert opinion Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

In the last decade, polysaccharide hydrogels have been extensively used in the development of novel drug delivery systems. Their excellent biocompatible and biodegradation characteristics as well as their green origin make them an appealing resource for their implementation. In this chapter, we sum up various polysaccharide hydrogels of diverse nature, combined or not with other polymers or drug delivery systems, implemented in the delivery of biotherapeutics as proteins, growth factors, gene vector, enzymes, hormones or monoclonal antibodies, with a special focus on pharmaceutical and biotechnological fields.

Background and importance Drug related problems (DRP) are common among hospitalised patients. During the COVID-19 pandemic, the number of inpatients increased and the pattern of drug use was varied which could lead to a higher number of potential DRP. Aim and objectives To describe DRP in patients admitted to COVID-19 wards during the COVID-19 pandemic peak. Material and methods A retrospective observational study was performed in a tertiary university hospital from 21 March to 30 April 2020. Patients included were those admitted to a COVID-19 ward and presenting a DRP (excluding emergency department and critical care units). Computerised physician order entry (CPOE) operates for all hospital beds. Medical prescriptions were revised daily by clinical pharmacists. When a potential DRP was detected, an annotation with a recommendation was made in the patient’s medical record. DRP were classified according to the Pharmaceutical Care Network Europe classification. Data collected were demographic, the drug class involved (anatomical chemical therapeutic (ATC)), DRP detected and degree of recommendation acceptance. Results Total patients with DRP: 291 (23.3%). Identified DRP: 393 (1.4 DRP/patient). 58.3% were men and median age was 63 (15.7) years. Conclusion and relevance Almost 25% of all patients had a DRP, presenting an incidence of 1.4 DRP/patient, higher than reported in previous series. 83% of evaluable recommendations were accepted. One- third of the recommendations were derived from a wrong dosage, and 15% from drug interactions. Hydroxychloroquine was the most frequently involved drug, probably because of the limited experience and wide spectrum of interactions, followed by antimicrobials such as ceftriaxone and azithromycin, used widely in respiratory tract infections. References and/or acknowledgements Conflict of interest No conflict of interest

Background and importance Patient adherence is a key determinant of treatment success in rheumatological immunomediated diseases. Available data about adherence to biological treatments and factors associated with non-adherence are limited in Spain. Moreover, no studies have compared adherence between subcutaneous and oral drugs. Aim and objectives To evaluate non-adherence to prescribed subcutaneous biologicals and oral drugs in patients with rheumatological immunomediated diseases and to assess possible predictor factors associated with treatment non-adherence. Material and methods A retrospective observational study was conducted in all patients receiving oral and subcutaneous treatment for rheumatological immune mediated diseases from 2017 to 2019 in the outpatient pharmaceutical care area of a tertiary university hospital. Non-adherence was evaluated by reviewing all scheduled drug dispensing visits in the computerised application. We considered non-adherent every time that a patient missed at least one drug administration. Data collected were demographic, total patients and patient treatments, total dispensing visits and route of administration for the drug dispensed in every visit. We classified patients as adherent and non-adherent considering the number of dispensing visits. In the non-adherent group, we recorded the number of dispensing visits, reasons for non-adherence, number of missed administrations per patient, and drug and predictor factors for non-adherence. Results 783 patients were included, aged 52.4 (13.7) years, 427 (54.5%) were women, 164 (20.9%) were smokers and 697 (89%) were Caucasian. 79 (10.1%) of 783 patients received more than one treatment. There were 869 patient treatments: 294 adalimumab (33.8%), 236 etanercept (27.2%), 78 golimumab (8.9%), 47 apremilast (5.4%), 39 certolizumab (4.5%), 34 secukinumab (3.9%) and 30 tocilizumab (3.5%). There were 9197 dispensing visits. Route of administration was 6406 subcutaneous (93.2%) and 374 oral (6.8%). Non-adherence analysis 2417 (26.3%) dispensing visits, reasons for non-adherence/dispensing visits: 92 unjustified (97.5%), 33 infection (1.4%), 18 surgery (0.7%), 3 pregnancy (0.1%), 6 other (0.3%). Number of missed administrations/patient treatments: 675 patients missed at least one administration (77.7%), mean 2.5 (±12.9) missed administrations. Number of missed administrations/drug: 9.9 baricitinib (±20.8), 15.8 tofacitinib (±31.2) and 25.4 apremilast (±53.2). Predictor factors for non-adherence: ethnicity (p=0.015), treatment with golimumab (p=0.006) and tocilizumab (p=0.036) and age (p=0.072). Conclusion and relevance Non-adherence to the prescribed drug occurred in 77.7% of patients with rheumatological immune mediated diseases. Demographic factors such as ethnicity as well as golimumab and tocilizumab treatment, despite their different frequency of administration, were predictors for non-adherence. Route of administration did not influence non-adherence. References and/or acknowledgements Conflict of interest No conflict of interest

Objective To evaluate the correlation and agreement in our unit and population of hemoglobin in gasometry versus hematology analyzer, to evaluate errors in transfusion or lack thereof. Results strong association between Point-of-care (POC) and hematimetry, with P Conclusions Low-moderate agreement of POC hemoglobin with standard haemothymetry. High probability of errors in the indication of transfusion based on gasometer hemoglobins, especially in low hemoglobins.

Resumen Objetivo Evaluar la correlacion y la concordancia en nuestra unidad y en la poblacion de la cifra de hemoglobina en gasometria versus hematimetria estandar; valorar errores en transfusion o falta de la misma. Resultados Fuerte asociacion entre los resultados del gasometro (POC) y la hematimetria, con p Conclusiones Concordancia baja-moderada de la hemoglobina del POC con la hematimetria estandar. Alta probabilidad de errores en la indicacion de transfusion en base a hemoglobinas de gasometro, sobre todo en hemoglobinas bajas.

Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range. However, it was replaced by a combination therapy of oral posaconazole plus iv caspofungin. Posaconazole allowed normalization of liver enzymes. After finishing posaconazole monotherapy on an outpatient basis, the patient made a full recovery. This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.

Background Relative value units (RVU) as a clinical management tool prove to be useful in measuring different pharmaceutical activities. However, little is known about RVU for the management of medication in special situations. Purpose To measure productivity in the management, dispensation, elaboration and pharmaceutical care activity of oncology medication in special situations: expanded or early access (EA) and ‘off-label’ use in a pharmaceutical department by estimating RVU. Material and methods Retrospective and observational study performed in a tertiary hospital. Data from all EA and off-label use oncology drugs requests were collected from January 2015 to February 2018 (38 months). Variables collected active drug, kind of drug in special condition (EA/’off-label’) and length of treatment. Pharmaceutical processes included: management, dispensation, elaboration and pharmaceutical care. RVU assigned to each activity have been obtained from a standardised document drawn up by the Spanish Society of Hospital Pharmacists.1 Results Seventy-five oncology drug requests were analysed, of which 58 (77.3%) were EA. Nivolumab nine (13%), pertuzumab/cabonzatinib seven (10%), bevazicumab/liposomal irinotecan six (9%) and trametinib/durvalumab five (7%) were the most requested. The average length of treatment was 5.9 months. Conclusion The pharmaceutical process with the highest productivity was elaboration of cytotoxic drugs. The processing of EA vs ‘off-label’ in oncology means 92.4% of total management activity. Reference and/or acknowledgements Grupo TECNO. Servicio de Farmacia Hospitalaria. Catalogo de productos y Facturacion. Madrid, 2009. No conflict of interest.

Background Drug injection-related pain is associated with a poor treatment adherence. To reduce it, a new subcutaneous formulation of adalimumab free of citrate and with a smaller volume injection and calibre needle has been brought to the market. Purpose The objective was to assess the influence of the treated pathology and associated factors on the pain reduction due to the switch to the new formulation of original adalimumab. Material and methods Prospective study performed during adalimumab’s formulation shift (2017) in the outpatient pharmaceutical care area of a tertiary hospital. All patients that had received both formulations were included and classified by the treated pahology. Pain was assessed by the patients through a visual analogue scale (VAS)(0–10 cm). Data collected: demographic, country of origin, injection site, administration frequency, number of doses before the switch, biologic-naive, VAS score pre- (VASPRE) and post- (VASPOST) formulation switch, concomitant medication. Statistics: median and interquartile range for quantitative (except age, mean (SD)), and% for qualitative variables. Association of several variables with pain reduction was checked through median regression models. Results Injection pain reduction (VASPOST–VASPRE) was statistically significant for all pathologies (p Statistically significant differences observed for: VASPRE: RA vs psoriasis (p=0.0403): IBD vs psoriasis (p=0.0207). Injection pain reduction (VASPOST–VASPRE): IBD vs psoriasis (p=0.0117). For IBD, antidepressants treatment (four patients, 10.81% of IBD cases) was the variable associated with the pain injection reduction (MD=−4.0; 95% CI: −7.26 to −0.74); p=0.018). No variables were identified for the other pathologies. Conclusion Most patients reported better tolerance to the new formulation of original adalimumab, independently of the pathology. Pain with the ancient formulation was higher in IBD and RA than in psoriasis patients, and pain reduction was higher in IBD than in psoriasis ones. In IBD patients, those receiving antidepressant had a lower perception of pain maybe due to the analgesic action of these drugs. It would be interesting to consider these pain reduction results when developing biosimilar adalimumab formulations. References and/or acknowledgements None. No conflict of interest.

Background A limited number of studies have evaluated medication adherence in psoriasis (PS) or psoriatic arthritis (PsA), reporting rates between 29% and 88% (medication possession ratio (MPR >80%)). However, until now no study has included apremilast as the evaluated drug. Purpose To evaluate adherence to apremilast treatment in patients with PsO and PsA, and to assess the possible factors associated with a MPR Material and methods Retrospective observational study including all patients beginning apremilast in an outpatient pharmacy service from a tertiary university hospital. Exclusion criteria: patients with less than one medication pharmacy refill (early discontinuation or recent treatment initiation). Data collected demographics, treatment indication, previous biological treatment, incidence of adverse events (AE) and adherence to apremilast using the MPR. Differences between patients with a MPR ≥100% vs. MPR Results Forty-one patients were included: 47 (23–68) years; male 56.1%; PsA 70.7%; and previous biologic therapy 26.8%. At least one adverse effect was reported in nine (21.9%) patients. Thirteen (31.7%) patients discontinued apremilast because of none-response, three (7.3%) for adverse events and one (2.4%) for loss of follow-up. Adherence was: MPR 100% in 22 (53.7%), MPR 90%–99% in 11 (26.8%), MPR 80%–89% in four (9.8%), MPR 70%–79% in two (4.9%) and MPR Conclusion Apremilast adherence rate was >90% in more than 80% of the patients. Considering MPR >80% reported in the literature, this rate was achieved in approximately 90% of patients, probably related to a multidisciplinary attention. The none factor was associated with a poorer adherence, however further studies including a greater number of patients are required. References and/or acknowledgements No conflict of interest.

Background:Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs.Objectives:To describe the HCRU and treatment costs in IMRD patients initiating subcutaneous tumour necrosis factor-alpha inhibitors (SC-TNFi) therapy, based on treatment persistence.Methods:Retrospective cohort study including all naïve patients initiating SC-TNFi therapy for IMRD from 2015-2018 in a tertiary university hospital.Patients were divided into two cohorts: persistent and non-persistent. Treatment persistence was estimated as the duration of time from SC-TNFi therapy initiation to discontinuation during one year of follow-up.SC-TNFi therapy and HCRU costs (outpatient care, rheumatology specialized outpatient care, inpatient care, emergency care, laboratory testing and other non- biological therapies) were calculated one year before and after initiation of SC-TNFi and compared between persistence and non-persistence groups.Results:110 patients were identified.Baseline characteristics: Non-persistent cohort (n=25) versus Persistent cohort (n=85): median age 48.6(12.7) vs 47.3(15.4) (p=0.692). Female (n=12;48%) vs (n=49;57.6%) (p=0.493). Race: Caucasian (n=22;88%), Asiatic (n=3;12%), Other (n=0;0%) vs Caucasian (n=75;88.2%), Asiatic (n=5;5.9%), Other (n=5;5.9%) (p=0.351).IMRD: RA (n=14;56%),PsA (n=2;8%), AS (n=4;16%), other spondyloarthropathy (n=5;20%) vs RA (n=34;40%),PsA (n=11;12.9%), AS (n=24;28.3%), other spondyloarthropathy (n=16;18.8%) (p=0.470). SC-TNFi therapy: adalimumab (n=4;16%), etanercept commercial (n=4;16%), etanercept biosimilar1 (n=5;20%), etanercept biosimilar2 (n=5;20%), golimumab (n=5;20%), certolizumab (n=2;8%) vs adalimumab (n=22;25.9%), etanercept commercial (n=11;12.9%), etanercept biosimilar1 (n=7;8.3%), etanercept biosimilar2 (n=10;11.8%), golimumab (n=24;28.2%), certolizumab (n=11;12.9%) (p=0.398).Overall cost of SC-TNFi treatment: Non-persistent 11218.81€ (6444.32), persistent 10470.19€ (3465.48); p= 0.658.Table 1.HCRU costsNon-persistent(n=25)Persistent(n=85)Total(n=110)PHCRU costs 12 months prior to SC-TNFi initiation,€(SD)Outpatient care243.48(828.86)87.17(293.61)122.70(471.20)0.204Rheumatology outpatient care216.39(169.88)174.79(101.06)184.24(120.55)0.224Inpatient care500.41(1542.93)170.34(846.47)245.36(1046.74)0.571Emergency care37.77(66.00)39.30(83.16)38.95(79.31) 0.850Laboratory testing376.12(195.59)388.20(207.07)385.46(203.70)0.458Other non-biological therapies10.77(39.83)36.79(250.55)30.88(221.01) 0.803Total1384.94(1816.17)896.60(1247.60)1007.59(1402.87)0.299HCRU costs 12 months post SC-TNFi initiation,€(SD)Outpatient care106.11 (172.85)76.67 (112.90)83.36 (128.67) 0.682Rheumatology outpatient care327.29(170.10)195.58(100.05)225.52(130.99)Inpatient care89.35(446.77)80.86(466.54)82.79(460.11) 0.969Emergency care89.14(171.89)36.06(106.23)48.12(125.31) 0.198Laboratory testing182.14(128.62)146.86(141.48)154.88(138.89) 0.061Other non-biological therapies3859.80(4043.86)25.89(116.05)897.24(2493.21)Total4653.84(4269.61)561.93(682.14)1491.91(2709.23)Conclusion:- Non-persistence was observed in less than a quarter of the patients.- No differences in the costs of SC-TNFi treatment were observed between the persistent and non-persistent groups, leading us to believe that persistence may not be associated with SC-TNFi costs offsets for patients with IMRD.- During the period post SC-TNFi initiation, the costs of rheumatologic outpatient care and treatment with other non-biological therapies as well as total costs were statistically significantly lower in the persistent cohort. These results suggest that persistence may be associated with HCRU cost savings for IMRD patients.Disclosure of Interests:None declared

Background:Patient adherence is a key determinant of treatment success in rheumatologic immune-mediated diseases. Available data about adherence to biological treatments and factors associated to non-adherence is limited in Spain. Moreover, no studies compare adherence between subcutaneous and oral drugs.Objectives:To evaluate non-adherence to prescribed subcutaneous biologicals and oral drugs in patients with rheumatologic immune-mediated diseases and to assess possible predictor factors associated to treatment non-adherence.Methods:Retrospective observational study including all patients with oral and subcutaneous treatment for rheumatologic immune-mediated diseases from 2017 to 2019 in the outpatient pharmaceutical care area from a tertiary university hospital. Non-adherence was evaluated by reviewing all scheduled drug-dispensing visits in the computerized application. We considered non-adherent every time that a patient missed at least one drug administration.Data collected: demographic, total patients and patient-treatments, total dispensing visits and route of administration for drug dispensed in every visit.We classified patients in adherent and non-adherent considering dispensing visits. Non-adherent group: number of dispensing visits, reasons for non-adherence, number of missed administrations per patient and drug and predictor factors for non-adherence.Results:783 patients included: 52.4(13.7) years; 427(54.5%) female; 164 (20.9%) smoker; 697 (89%) Caucasian.A total of 79 (10.1%) of 783 patients received more than one treatment.869 patient-treatments: 294 adalimumab (33.8%), 236 etanercept (27.2%), 78 golimumab (8.9%), 47 apremilast (5.4%), 39 certolizumab (4.5%), 34 secukinumab (3.9%), 30 tocilizumab (3.5%).9,197 dispensing visits. Route of administration: 6,406 subcutaneous (93.2%), 374 oral (6.8%).Non-adherence analysis: 2417 (26.3%) dispensing visits, reasons for non-adherence/ dispensing visits: 92 unjustified (97.5%), 33 infection (1.4%), 18 (surgery) 0.7%, 3 pregnancy (0.1%), 6 others (0.3%).Number of missed administrations/patient treatment: 675 patients missed at least one administration (77.7%).Mean 2.5 (±12.9) missed administrations.Number of missed administrations/drug: 9.9 baricitinib (±20.8), 15.8 tofacitinib (±31.2), 25.4 apremilast (±53.2).Predictor factors for non-adherence: ethnicity (p=0.015), treatment with golimumab (p=0.006), and tocilizumab (p=0.036). Age (p=0.072).Conclusion:- Non-adherence to the prescribed drug occurred in 77.7% of patients with rheumatologic immune-mediated diseases- Demographic factors such as ethnicity as well as golimumab and tocilizumab treatment, despite their different frequency of administration, were predictors for non-adherence- Route of administration did not influence non-adherence.Disclosure of Interests:None declared

Background Hospitals cannot include all marketed drugs in their formularies. Those drugs not included in the formulary (NFD) need an alternative drug available (ALT) in order to cover all patient requirements. Purpose To assess the prevalence of NFD prescriptions and factors associated with the acceptance recommendation on an ALT. Material and methods Retrospective study performed in a tertiary university hospital from 2012 to 2015. Data collected: drug-related problems (DRP); DRP-related NFD prescription (DRP-NFD); admissions; and admissions with prescription of NFD. NFD classification: NFD with ALT (NFD-ALT) (drug able to present the same clinical effect and safety profile than NFD); non-replaceable NFD (NFD-NR) (drug for which no therapeutic alternative is available); or NFD of doubtful therapeutic efficacy (NFD-DTE) (drug with limited evidence on its effectiveness). Clinical pharmacists made an annotation in the electronic medical record, offering an ALT when it was available, proceeding to its acquisition when it was NFD-NR and recommending withdrawal when it was NFD-DTE. Admissions data collected: demographic; Charlson comorbidity index; urgent/scheduled admission; surgical/medical service; number of concomitant drugs; and ATC-group. Acceptance of ALT recommendation was evaluated. Results Total admissions: 69,686; DRP: 10,480; admissions affected by DRP-NFD: 441 (0.6%). DRP-NFD: 557 (5.1%), where: NFD-ALT: 496 (89%); NFD-NR: 5 (0.9%); NFD-DTE: 56 (10.1%). Most commonly involved ATC groups: urological preparations (G04):71 (16.1%); renin-angiotensin system (C09): 47 (10.7%); agents against obstructive airway diseases (R03): 47 (10.7%); ophthalmologic (S01): 43 (9.8%); hypolipidaemic (C10): 25 (5.7%); systemic antihistamines (R06): 20 (4.5%); systemic corticosteroids (H02): 17 (3.9%); diuretics (C03): 16 (3.6%); laxatives (A06): 12 (2.7%); anti-inflammatory/antirheumatic (M01): 11 (2.5%); others: 132 (29.9%). From 496 NFD-ALT, 154 (31%) recommended ALT were accepted, 287 (57.9%) not accepted and 55 (11.1%) were non-evaluable. Conclusion Most drugs not included in the formulary are substitutable for an available alternative (99.1%). Although no factors are significantly associated, there is a trend towards acceptance of the recommended therapeutic alternative in patients with prescription of a higher number of concomitant drugs. Acceptance was less than 30% when the ATC involved were systemic antihistamines, ophthalmologic preparations and agents used against obstructive airway diseases. No conflict of interest

BACKGROUND: HIV-infected patients have a higher cardiovascular risk (CVR) than the general population. However, there are not specific preventive interventions for lifestyle modification for this population group. In addition, those treated with protease inhibitors (PIs) may also present dyslipidaemia and require a lipid-lowering-therapy with statins. PURPOSE: To evaluate which factors linked to cardiovascular disease are independently associated with achieving target lipid levels (TLL) (low-density lipoprotein cholesterol

Endometrial cancer (EC) is the most common gynecological cancer in developed countries. Most patients are diagnosed at an early stage with a low risk of relapse. However, there is a group of patients with a high risk of relapse and poor prognosis. Despite the recent publication of randomized trials, the adjuvant treatment of high-risk EC is still to be defined and there are many open questions about the best approach and the right timing. Unfortunately, the survival of metastatic or recurrent EC is short, due to the poor results of chemotherapy and the lack of a second line of treatment. Advances in the knowledge of the molecular abnormalities in EC have permitted the development of promising targeted therapies.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries. Most patients are diagnosed at an early stage with a low risk of relapse. However, there is a group of patients with a high risk of relapse and poor prognosis. Despite the recent publication of randomized trials, the adjuvant treatment of high-risk EC is still to be defined and there are many open questions about the best approach and the right timing. Unfortunately, the survival of metastatic or recurrent EC is short, due to the poor results of chemotherapy and the lack of a second line of treatment. Advances in the knowledge of the molecular abnormalities in EC have permitted the development of promising targeted therapies.

To evaluate the correlation and agreement in our unit and population of hemoglobin in gasometry versus hematology analyzer, to evaluate errors in transfusion or lack thereof.strong association between Point-of-care (POC) and hematimetry, with P.001, with a coefficient of determination rLow-moderate agreement of POC hemoglobin with standard haemothymetry. High probability of errors in the indication of transfusion based on gasometer hemoglobins, especially in low hemoglobins.

A 36-year old primigravid of 41 weeks gestation was admitted to the labour ward. Her past medical history included hyperemesis gravidarum and migraine. An accidental dural puncture occurred during labour epidural analgesia. In the postpartum period she presented with continuous headache, and was treated with oral analgesics, oral caffeine, fluid therapy, and tetracosactide. She refused an epidural blood patch. On the seventh day postpartum, the patient was re-admitted to the Emergency Department with decreased level of consciousness and signs of brainstem compression. Cranial computed tomography and magnetic resonance imaging showed a posterior fossa tumour. An emergency craniotomy was performed with complete neurological recovery. This case emphasises the need to consider the differential diagnoses of post-dural puncture headache and to highlight the warning signs in patients who do not respond despite treatment with conventional therapy.

a b s t r a c t Objective: To describe the clinical impact of PET/CT in the management of patients with vulvar cancer. Material and methods: Retrospective analysis of 13 PET/CT studies with

Background Continuous vancomycin infusion (CVI) is frequently used to achieve therapeutic levels (15–25 mg/L) in patients in whom, related to their physiological characteristics (young, obese or critical patient), intermittent infusion (II) would need higher doses than those recommended (>4 g/day). Latest guidelines suggest a target of 15–20 mg/L but there is controversy over vancomycin associated nephrotoxicity in CVI. Purpose To determine the frequency of nephrotoxicity associated with CVI and to identify risk factors. Material and methods A retrospective cohort study was performed in a 400 bed tertiary university hospital from January 2013 to August 2016. Patients included adults treated with CVI. Dose recommended to achieve steady state concentration (Css) was 15–20 µg/mL. Data collected: demographics, body mass index (BMI), type of infection, treatment duration, vancomycin Css and AUC, dose recommended, initial and final renal function (SCr) and glomerular filtration rate (GFR) using CKD-EPI, nephrotoxicity defined by RIFLE criteria (risk, injury, failure, loss and end stage renal disease), nephrotoxic drugs and others causes of nephrotoxicity. Pharmacokinetic analysis: Bayesian estimation compartmental model (PKS System Abbott). Data are shown as median (Q1–Q3). Statistical analysis: SPSS Statistics Base 22.0. Results 38 patients were included: 25 (65.8%) men, 55 (43–64) years, 78 (70–89) kg, BMI 26 (24–32) kg/m 2 , critically ill 7 (18.4%). Type of infection: bone 22 (57.9%), diabetic foot 4 (10.5%), bacteraemia 4 (10.5%), CNS 4 (10.5%), abdominal 2 (5.3%) and others 2 (5.3%). Treatment duration: 9 (6–13) days. Css: 23.4 (19.6–28.1) µg/mL. AUC: 506 (435–575) µg×h/mL. Recommended dose: 3.2 (2.8–3.5) g/day. Renal function: Scr initial 0.53 (0.41–0.73) mg/dL, final 0.58 (0.47–0.78) mg/dL. GFR initial 113 (102–129) mL/min, final 107 (98–121) mL/min. Nephrotoxicity: 1 (3.8%). RIFLE 1-0-0-0-0. Risk factor: leg amputation. Nephrotoxicity was reversible. Adverse effects: phlebitis 1 (3.8%) with dropout due to adverse effect. Conclusion CVI allows therapeutic levels (15–20 mg/L) to be to achieved, especially in bone infections. Despite an increased steady state concentration, nephrotoxicity was negligible with therapeutic drug monitoring. Phlebitis can make it difficult to administrate CVI. References and/or acknowledgements Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm2009;66:82–98. No conflict of interest

The objective of this review is to recognize the characteristics of endometrial adenocarcinoma in young patients and to evaluate the published experience with conservative approach in patients with endometrial adenocarcinoma. We searched MEDLINE articles describing patients with endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and January 2007. Endometrial carcinoma in patients under 45 years of age is an unusual condition that shows a more favorable pattern than in older patients. One hundred thirty three patients were found in the search. The average duration of hormonal therapy was approximately 6 months. The average response time was 12 weeks. Seventy six percent of patients treated with hormonal therapy had a complete response and the other 24% never responded to treatment. Of those who initially responded, 66% didn't show recurrence of disease. The other 34% had a relapse. There have been published 4 deaths of patients conservatively managed. A conservative approach in these patients can offer reasonable oncological security and the opportunity of fulfilling their maternal desires in selected cases. However, consideration should be taken regarding the potential adverse outcomes that have been recently published in the literature.

This article review the current situation of the exenterative procedures as part of the treatment of recurrent cervical cancer after radiation. Pelvic exenteration has been proven the only curative choice of treatment in selected cases of this clinical situation. A review of historical and recent published series have shown an increase of 5-y survival from 30 to 42 %. Almost one out of two patients will suffer complications of some kind, and one out of three will have a severe complication with pelvic exenteration. During the past sixty years, a number of outstanding improvements have been achieved - not only in surgical outcomes, but also in quality of life - owing to new reconstructive approaches. Women facing an exenterative procedure must be counseled carefully about the risks and long-term concerns related to the procedure. Each should undergo a comprehensive evaluation to make sure there is no evidence of unresectable or metastatic disease that would make her an unsuitable candidate for exenteration.

Carcinoma of the uterine cervix is a frequent common cancer in women. Patients diagnosed with early stage cervix cancer are managed with surgery. Overall survival for stage IB (IB1-IB2) and IIA, is in the range of 80-90% at 5 years. Only patients with poor prognostic factors as: large tumors (>or=4 cm), positive lymph nodes, positive and/or close margins

The role of neoadjuvant chemotherapy (NACT) in cervical cancer has been a matter of investigation over the last 20 years. A systematic review and meta-analysis of individual patient data (IPD) demonstrated that NACT followed by surgery is superior to radiotherapy alone in terms of overall survival. However, in spite of the results of the meta-analysis, NACT has not been adopted as the new standard of care. In the present paper, we review the reasons why NACT is still considered an investigational approach in cervical cancer.

Objective To describe the clinical impact of PET/CT in the management of patients with vulvar cancer. Material and methods Retrospective analysis of 13 PET/CT studies with 18 F-FDG (6 staging and 7 suspected recurrence) corresponding to 10 patients diagnosed with vulvar cancer by biopsy, with a mean age of 64.5 years. The preoperative PET/CT study was analyzed qualitatively according to the lesion region. Surgical excision was carried out, covering all the suspected areas according to the PET/CT study. This was compared with the histopathologic analysis. Results Abnormal vulvar PET/CT uptake was found in 9 out of the 13 studies and invasion of adjacent structures in 5 of them (urethra, perianal, vagina). The inguinal–femoral lymph nodes were considered as affected in 3 studies and one pelvic lymph node was also affected. Four of the studies had extralymphatic involvement: 3 in lung and 1 in ischiorectal fossa. The PET/CT showed a 100% sensitivity for the detection of the vulvar lesion in squamous cell carcinomas and 60% in non-squamous cell ones. There was a false positive result for local invasion due to urine contamination. One of the studies with lung metastases was related to a synchronous breast tumor. All the pathological lymph node levels detected in the PET/CT study were confirmed in the histopathology study. No new lesions were identified by surgery. PET/CT changed the therapeutic management in 8/13 studies (61.5%). Conclusions PET/CT is postulated as a useful imaging test for the management of vulvar cancer, mainly in the identification of nodal metastases. It may affect both surgical planning and clinical management. Larger series are needed to confirm our findings.

A 36-year old primigravid of 41 weeks gestation was admitted to the labour ward. Her past medical history included hyperemesis gravidarum and migraine. An accidental dural puncture occurred during labour epidural analgesia. In the postpartum period she presented with continuous headache, and was treated with oral analgesics, oral caffeine, fluid therapy, and tetracosactide. She refused an epidural blood patch. On the seventh day postpartum, the patient was re-admitted to the Emergency Department with decreased level of consciousness and signs of brainstem compression. Cranial computed tomography and magnetic resonance imaging showed a posterior fossa tumour. An emergency craniotomy was performed with complete neurological recovery. This case emphasises the need to consider the differential diagnoses of post-dural puncture headache and to highlight the warning signs in patients who do not respond despite treatment with conventional therapy.

Locally advanced cervical carcinoma had been treated with radiation therapy until 1999, when five different large clinical trials showed an overall survival benefit when chemotherapy was administered concomitantly with radiotherapy. The chemotherapy agents used in these trials were cisplatin, cisplatin combined with fluorouracil or hydroxyurea. Weekly cisplatin (40 mg/m 2 ) achieved the best responses, even when compared with the combination with fluorouracil. These results led the United States National Cancer Institute (NCI) to recommend platinum-based chemotherapy for the treatment of locally advanced cervical carcinoma. Other cytotoxic agents have been tried in combination with radiotherapy for the management of the disease, including carboplatin, paclitaxel, gemcitabine and even topotecan. Gemcitabine has shown promising results and the combination of paclitaxel and carboplatin has proved safe and effective. However, to date, there has been no agent or combination of agents to have shown superiority over weekly cisplatin. Biologic agents such as bevacizumab, cetuximab, sorafenib and erlotinib are currently being tried in different trials in combination with radiotherapy and cisplatin. Celecoxib, a COX-2 inhibitor was evaluated in an RTOG study in combination with cisplatin and flourouracil with radiation therapy with no apparent effect on DFS and poor rates of locoregional control. Chemoradiation is the current standard therapy in locally advanced cervical carcinoma. The integration of novel agents will be established by the ongoing clinical trials.

Background Despite current highly active antiretroviral therapy (HAART), some patients still do not achieve an undetectable viral load, and it is important to identify treatment failure (TF) associated factors. Purpose To determine the incidence and risk factors for TF in a cohort of HIV infected patients. Material and methods Cross sectional study in an initial cohort of 1562 HIV infected patients from June 2014 to July 2015. 1259 were finally included and interviewed, to collect the following data: demographics, current ART and adherence, concomitant medications and drug interactions (DI) (according to the University of Liverpool database). TF was defined as confirmed HIV RNA >50 copies/mL. A logistic regression analysis was used to identify variables independently related to TF. Results Patients included: 1259 (80.6%); patients excluded: 303 (19.4%) due to lack of data or lost to follow-up. Univariate analysis Patients with and without TF: 151 (12.0%) versus 1108 (88.0%), male (82.1% vs 80.1%, p = 0.587), age (42.9 vs 48.0 years, p + T cell count (526.0 vs 716.3 cells/µL, p HAART: non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI) (35.8% vs 55.0%, p Adherence 90 (8.1%), p Goodness-of-fit: Hosmer and Lemershow test (p = 0.889). Discriminative ability: AUC 0.744 (95% 0.702 to 0.787), p Conclusion Risk factors related to treatment failure were younger age, alcohol or drug use, poor adherence and use of HAART not including an NNRTI. Despite advances in HIV treatment, poor adherence is still the most important factor for treatment failure and justifies the need for multidisciplinary management of these high risk patients. No conflict of interest.

Background Monoclonal antibody drugs (mAb) are a relative new innovation and have been established as one of the most successful therapeutic strategies in several pathologies. The novel mechanism of action, based on modulation of the immune system, is associated with higher cure rates. Consequently, mAb are considered an attractive therapeutic option and are the subject of study in several clinical trials (CT). Purpose To assess the impact of mAb CT related to total CT managed at the pharmacy department, and different services involved in them. Material and methods Retrospective observational study performed in a tertiary university hospital from January 2014 to September 2015. Data collected: total CT and mAb CT (mAb-CT) by department; mAb-CT/total mAb-CT by department; mAb-CT phase. Reference sources were an internal database, the EU Clinical Trials Register and the American Clinical Trials Database. Results Conclusion More than half of clinical trials from dermatology, rheumatology and cardiology services are evaluating mAb. Considering total mAb-CT, oncology and haematology services are involved in approximately 60% of them. Approval of these mAb is imminent, as more than two-thirds of CT are phase III and will be commercialised soon. Benefit of mAb has been linked to certain pathologies. Consequently, some services with intense research activity have a reduced number of mAb-CT. No conflict of interest.

Background Interferon free treatments (IFT) for chronic hepatitis C (CHC) consist of more feasible and better tolerated regimens that could help to improve adherence. Nevertheless, little is known about adherence to these treatments in clinical practice. Purpose To evaluate adherence to IFT in clinical practice and non-adherence risk factors. Material and methods Patients completing IFT for CHC in a tertiary hospital were included (December 2014 to September 2015). Baseline characteristics including concomitant medications were recorded. Adherence was calculated as a percentage from pill count records performed in each drug dispensing visit (every 4 weeks) and at the end of treatment. Ribavirin dose reductions were not considered as lack of adherence. Bivariate analysis of baseline characteristics in patients with and without 100% adherence was performed. Fisher’s test and the Mann-Whitney U test were used for categorical and continuous variables, respectively. Results 78 patients were included: median age was 59 years, 55 (70.5%) were male, 48 (61.5%) with genotype 1b, 15 (19.2%) with HIV coinfection, 53 (67.9%) with cirrhosis and 36 (46.2%) were naive. Mean number of concomitant drugs was 3.31 (SD 2.7). 69 (88.5%) patients received 12 weeks of treatment. No differences were found in demographics, genotype, HIV coinfection, previous antiviral treatment or number of concomitant medications between patients with and without 100% adherence. Conclusion Observed adherence rates to all IFT in clinical practice were superior to 90%. None of the analysed factors seemed to influence patient adherence, probably due to the low number of patients and the excellent rates of adherence observed. References and/or Acknowledgements Pawlotsky JM. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015 No conflict of interest.