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Marta H Hernandez1,2 *, Valentin Bote3 *, Alexandre Serra-LLovich,1 Marc Cendros,1,4 Juliana Salazar,5 Conxita Mestres,2 Silvina Guijarro,3 Aida Alvarez,3 Cristina Lamborena,3 Iria Mendez,3 Bernardo Sanchez,3 Amaia Hervas,3 Maria J Arranz1,2 1Research Laboratory Unit, Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain; 2School of Health Sciences Blanquerna, University Ramon Llull, Barcelona, Spain; 3Department of Child and Adolescent Psychiatry, Hospital Universitari Mútua Terrassa, Terrassa, Spain; 4EUGENOMIC Genómica y Farmacogenética, Barcelona, Spain; 5Translational Medical Oncology Laboratory, Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Maria J Arranz, Research Laboratory Unit, Fundació Docència i Recerca Mútua Terrassa, c/Sant Antoni, 19, Terrassa, 08221, Spain, Tel +34 937 36 50 50, Fax +34 93 736 50 21, Email mjarranz@mutuaterrassa.esPurpose: Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40– 70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphenidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety.Patients and Methods: A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (SLC6A2) and for its primary metabolic pathway (CES1) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype.Results: Single marker analyses considering gender, age, and dose as covariates showed association between CES1 variants and MPH-induced side effects (rs2244613-G (p=0.04), rs2302722-C (p=0.02), rs2307235-A (p=0.03), and rs8192950-T alleles (p=0.03)), and marginal association between the CES1 rs2302722-C allele and presence of somnolence (p=0.05) and the SLC6A2 rs36029-G allele and shutdown (p=0.05). A CES1 haplotype combination was associated with efficacy and side effects (p=0.02 and 0.03 respectively). SLC6A2 haplotype combination was associated with somnolence (p=0.05).Conclusion: CES1 genetic variants may influence the clinical outcome of MPH treatment in ASD comorbid with ADHD children and adolescents.Keywords: CES1, SLC6A2, autistic spectrum disorders, ASD, methylphenidate, attention deficit hyperactivity disorders, ADHD

Objectives Pharmacists’ care has an essential role in multidisciplinary teams in charge of chronic patients. However, data available on the clinical outcomes of these activities appear inconclusive. This study aimed to systematically investigate the effect of multidisciplinary teams that include coordinated pharmaceutical care on clinical outcomes. Design Systematic review and meta-analysis. Relevant studies identified from MEDLINE, Cochrane, Web of Science, Scopus and CINAHL databases were analyzed. The search included randomized clinical trials published in 2000-2018. Included studies were all published studies in English that compared the effectiveness of multidisciplinary teams including pharmacist care to usual care. Meta-analysis was carried out using a random effects model, and subgroup analysis was conducted to determine the sources of heterogeneity. Setting and Participants 29 studies involving 4186 adult patients were included. Measures Follow-up time varied from 30 to 180 days. The most common primary endpoint was the frequency of hospitalizations or readmissions, followed by variation in clinical parameter variables related to quality of prescription, treatment adherence and costs. Results Twelve (41.3%) of the included studies scored low risk of bias according to the AMSTAR-2 scale, the remaining 17 (58.7%) being classified as intermediate risk. The intervention of a multidisciplinary team reduced the probability of readmission by 32% [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.62-0.89]. Six of the 29 (20.7%) studies included met the inclusion criteria of the meta-analysis on quality-of-life outcomes. The intervention of the multidisciplinary team represented a significant increase in patients’ quality of life (OR 0.58, 95% CI 0.47-0.69). Analysis of heterogeneity showed a significant difference between the studies. No evidence of publication bias was identified. Conclusions and Implications Multidisciplinary programs that include pharmaceutical care reduce the risk of visiting hospitals and improve patients’ quality of life. This review supports the importance of the pharmacists as part of multidisciplinary teams.

Aim: Older patients with chronic hepatitis C infection starting direct-acting antivirals (DAAs) are frequently prescribed multiple medications that may be categorized as inappropriate. Anticholinergic burden has been shown to be a predictor of adverse health and functional outcomes. Different scales are available to calculate anticholinergic burden. The aim of this study was to determine the prevalence of anticholinergic medication among older patients treated with DAAs and the risk factors associated using the Anticholinergic Cognitive Burden (ACB) scale, the Anticholinergic Risk Scale (ARS) and the Anticholinergic Drug Scale (ADS) and analyze the resulting safety consequences. Methods: Observational, retrospective cohort study of consecutive patients &ge, 65 years old receiving DAAs and taking concomitant medication. This study was conducted in accordance with the Strengthening the Reporting of observational studies in Epidemiology Statement. Results: 236 patients were included. The average age was 71.7 years, 73.3% cirrhotic, and 47% patients took &ge, 5 medicines. According to the ACB, ARS and ADS scales, 35.2% (n = 83), 10.6% (n = 25) and 34.3% (n = 81) of the patients were treated with anticholinergic medication. Two hundred-and-six (86%) patients presented any adverse events (AEs) during therapy. ARS scale showed a significant relationship between presence of anticholinergic medication and AEs. A large number of patients suffered anticholinergic events, with more events per patient in patients taking anticholinergic drugs. Conclusions: Older hepatitis C chronic patients are exposed to potentially inappropriate polypharmacy and anticholinergic risk, according to the ACB, ARS and ADS scales. The three scales showed different results. Only the ARS scale was associated with AEs, but the rate of anticholinergic effects per patient was significantly higher in patients with anticholinergic drugs, regardless of the scale used. Consider quality of pharmacotherapy when starting DAA with a multidisciplinary approach could improve health outcomes.

Background Patient safety is the most important concern for healthcare professionals, patients and healthcare systems. Adverse drug events (ADEs) are a common cause of hospitalisation and occur with increasing frequency in hospital as patients age. Purpose Determine the ADEs at admission and during the stay in a psychogeriatric unit. Material and methods One-year prospective cross-sectional study (July 2015–2016), in a psychogeriatric ward (21 beds). Included patients with dementia, admitted presenting neuropsychiatric/behavioural and psychological symptoms in dementia (BPSD). Excluded patients with previous psychiatric illness or palliative conditions. Prescription information: Aegerus and Catalonia clinical record HC3. Variables: demographics, diagnoses, Global Deterioration Scale (GDS-R), functional assessment (Barthel Index), fall risk (Downton JH and Tinetti). Anticholinergic risk level (Drug Burden Index (DBI). ADE assessment: causality by Naranjo algorithm, severity by classification system of the Institute for Healthcare Improvement and preventability by the Schumock–Thornton algorithm. Drugs classification by the Anatomical Therapeutic Chemical Code (ATC). Results Sixty patients (60% females), age: 84.8 years (68–96). Dementia: unidentified (43%), Alzheimer’s (31%), Lewy bodies (8%), vascular (8%), mixed (5%) and others (6%). GDS-R 4.5 (±1.2), moderate cognitive impairment. Barthel Index 43.8 (±23.9), moderate dependence. Patients comorbidities 4.8 (±1.6). Drugs/patient 9.03 (±3.12). DBI high risk in 69% of the patients. High risk of falls, Tinetti (15.5±8) and Downton test (4.5±1.3). Sixty-eight ADEs (53 patients, 81.5%, 22.6% more than one). 73.5% not related to falls. From this 80% were related to the ATC nervous system (46% (23 ADE) psycholeptics). Naranjo algorithm one definite (2%), probable 45 (90%) and possible four (8%). Severity Category E: temporary harm to the patient and required intervention in 34 (68%) and F: temporary harm to the patient and required initial or prolonged hospitalisation in 16 (32%). Schumork–Thornton test 58% (29) of the ADE were preventable, possibly preventable 6% (three) and unavoidable 36% (18). Main ADE drowsiness/somnolence 27.7%, 12.8% weakness and hypoactivity and 10.7% hypotension. DBI significant differences related to fall as ADE result (fall group 1.288±0.79, non-fall group 0.95±0.71 p=0.05). Conclusion The balance between effective treatments and safety is complex in these patients. Mostly ADE are related to the pharmacological treatment of this BPSD. Anticholinergic load is a determinant for a specific ADE and were related to falls, the worst consequence in this patient, clinical and economic impact. References and/or acknowledgements No conflict of interest.

Older people usually present with adverse drug events (ADEs) with nonspecific symptoms such as cognitive decline, recurrent falls, reduced mobility, and/or major deterioration. The aims of this study were to assess the ADEs of patients with dementia and presenting neuropsychiatric/behavioral, and psychological symptoms in dementia (BPSD) and to categorize and identify the principal factors that allow to prevent ADEs, and separately ADEs that result in falls. To that end, a one-year prospective study in a psychogeriatric ward (July 2015 to July 2016) was performed. All patients admitted to this ward were eligible for enrolment. Patients who met any of the following criteria were excluded from the study: Patients without cognitive impairment, a length of stay under 7 days, and palliative or previous psychiatric pathology. We included 65 patients (60% women, 84.9 years &plusmn, 6.7) with mild to moderate cognitive impairment, moderate to severe functional dependence, and a high prevalence of geriatric syndromes and comorbidity. A total of 87.7% were taking five or more drugs (mean 9.0 &plusmn, 3.1). ADEs were identified during the interdisciplinary meeting and the follow up by clinical record. Sixty-eight ADEs (81.5% patients) were identified, of which 73.5% were not related to falls. From these, 80% were related to drugs of the nervous system. The Naranjo algorithm determined that 90% of ADEs were probable. The severity of the ADEs was Category E in 34 patients (68%). The number of preventable ADE according to the Schumork&ndash, Thornton test was 58%. The main ADE was drowsiness/somnolence (27.7%). ADEs related to falls represented a 26.5%. The balance between effective treatment and safety is complex in these patients. A medication review in interdisciplinary teams is an essential component to optimize safety prevention.

Background: To introduce and manage a Pharmaceutical care programs in geriatric care institutions presents difficulties such as reduced pharmacy service staff, complexity of the patients or lack of integration of the pharmacist in the health care team. This work describes the evolution of the implementations of a program of pharmaceutical care centered in drug related problems (DRP) in a group of geriatric institutions of different levels of complexity. Methods: Setting: Long-term and subacute care hospitals (HSS) and Health care teams attending nursing homes (EARs). Participants: Patients attended in HSS and EARs during different periods between 2010 and 2016. Interventions: The program was developed in different stages, in which pharmacists made interventions of increasing complexity. Results: Between 2010 and 2013, the approach was only to improve the prescription of non-appropriate drugs for the elderly, which was reduced from 19 to 14.5%. Subsequent steps included detection of drug-related problems (DRP), systematization of treatment revisions, recording of pharmacist interventions, improvements in the classification of interventions and the creation of a web-based database for recording in a more efficient way. During these years, there was an increase in the number of patients included in pharmaceutical care activities and thus the number of pharmacist interventions (3872 in 2014 vs 5903 in 2016). In 2016, mean age in 2016: 83.2 years old. Mean number of medicines/patient: 8.4 ± 3.3, and mean interventions/patient: 1.62. Degree of acceptance of the interventions by physicians improved (68.6% in 2016 vs 45.5% in 2012), even though there is still much work to do. The Medication Appropriateness Index (MAI) showed that when the interventions were accepted, there was an important improvement. HSS mean MAI values pre-intervention: 2.52, post-intervention 0.80. In EARs: 5 pre and 1.39 post. In both cases p < 0.0001. Conclusions: Approaching the deployment of activities in a progressive way has made us more efficient and able to confront and solve the problems that have arisen. Even though there has been a very restricted increase in the staff and budget, we are able to implement a DRP detection programme with guaranties of quality.

BACKGROUND: Medication reconciliation (MR) and review reduce drug-related problems (DRP) and improve patient safety. The elderly population is at risk of DRP during transitions through different levels of healthcare. Pharmacists giving pharmaceutical care in long-term facilities could detect this problem and improve treatment quality and patient safety. PURPOSE: Detect and classify DRP in long-term care institutions and evaluate the impact of clinical interventions in quality prescription in order to improve patient safety. Give pharmaceutical care focused on the person by detecting and quantifying the DRP and evaluate the impact of the interventions. MATERIAL AND METHODS: Prospective study conducted in intermediate care hospitals and long-term care institutions (336 beds). All treatments were reviewed at patient admission (all patients included). DRP were detected and taken into account was the actual prescription, previous discharge reports and controls, and medical history. The DRP were classified by the American Society of Health-System Pharmacists (ASHP).(1) Problems and discrepancies were notified to the clinician during the first 48 hours after patient admission. The impact of the interventions in prescription quality was evaluated through the Medication Appropriateness Index (MAI).(2) All interventions were managed by PowerPivot(®) software. RESULTS: Study period July 2016 to August 2017, 1832 patients were reviewed. Mean age 81 (105–39 years-old), 60% females. Average drugs per patient 8.85±4.03. In 880 patients, 1370 interventions were conducted (952 patients no problem was found). DRP: 1,074 (82%). Most frequent: omissions 16%, inappropriate drugs (13%) and schedule (10%). Medication errors: 240 (18%). Degree of acceptance of pharmaceutical interventions 75%. Impact of interventions accepted, MAI scores per drug, improved from 2.99 to 0.95 (p

Objectives To establish a medication review programme in geriatric patients in nursing homes. Methods 70 nursing homes, attended by 8 healthcare teams; two consultant pharmacists provide training and support. Prospective study, conducted between August and December 2013, consisting in patients medication profile review, using an algorithm developed by the Pharmacy Department. Drug-related problems (DRP) were communicated to physicians and documented using the Pharmaceutical Care Network Europe scheme. Medication appropriateness index (MAI) score was calculated before and after the pharmacist9s interventions. Results Medication profiles of 127 patients (mean age 84 years) were reviewed. 424 DRP were detected, the majority related to potential adverse drug events. Pharmacists’ interventions/recommendations were made mainly at prescription level. Lack of indication for the drug prescribed in the clinical record was a recurrent problem, thus indicating a somewhat poor quality in these records. Potentially inappropriate drug prescription was also a common problem (17.6%). Cardiovascular, alimentary tract and metabolism and nervous system drugs were those with more DRP. Degree of acceptance of interventions was 80%. The principal cause of non-acceptance was when the drug has been prescribed by a specialist. Number of drugs per patient dropped from 10.3 to 9.5, and the mean MAI score dropped from 5.4 to 1.3. Conclusions The incorporation of consultant pharmacists at nursing home level has led us to know the quality of prescription and the DRP. We have established a multidisciplinary team that works for the improvement of drug use.

Objectives To determine the prevalence of potentially inappropriate prescribing in our long-term care institutions with limited experience of pharmacists’ interventions. To apply preventative measures, based on pharmacists’ recommendations, to obtain better outcomes for our patients. Methods Patients were aged >75 years. The study consisted of a retrospective assessment of the prescription of these drugs (July–December 2010: 600 patients), an educational and informative programme to physicians (2011), followed by application of pharmacists’ recommendations (March–November 2012: 1048 patients), based on Beers criteria. Results In the retrospective period, at least one potentially inappropriate drug was prescribed for 19% of patients. Patients receiving temporary care for long-term disease (temporary long-term care) and continuing long-term care (LTC) were prescribed a higher proportion of potentially inappropriate drugs (46.5% and 36.0%, respectively). During the intervention period inappropriate drug prescription dropped to 14.5%. Physicians ‘acceptance of the recommendations made by pharmacists’ was 45.5%. Acceptance was lower in temporary LTC and subacute care. Fourteen different potentially inappropriate drugs were prescribed in both periods. Amiodarone and hydroxyzine are among the drugs which are more difficult to change. Conclusions Revision of treatments by pharmacists and their subsequent recommendations to physicians improves the quality of treatments. Physicians are now more aware of the importance of pharmacists’ interventions and a new stage of wider interventions and recommendations has begun. An algorithm has been established that standardises pharmacist interventions and leads to continuing improvement.

Introduction: Pharmacists have been progressively included in health care teams delivering integrated care. With the development of Pharmaceutical Care, pharmacists provide direct medication-related care with the aim of improving patient’s life quality. However, even thought these progresses (especially in hospitals), most day to day work in integrated care is centered on physician’s and nurses.Benefits of integrated care are higher in the patients with most complex health care needs, such as older people. This group of population is characterized by its frailty, comorbidities and polypharmacy; therefore problems related with medication (PRM), are more frequent and have more serious impact.Our Group is specialized in giving health care to older people at different levels: primary, nursing homes, long term care, home care; areas where the participation of pharmacist in the integrate care is usually underdeveloped. Therefore, there is less evidence on the benefits derived from pharmacist’s intervention; compared with other health care institutions such acute care hospitals.From our Pharmacy Service, we have been working in the incorporation of the pharmacist as a member of the care team in order to improve outcomes in our patients through the management of medication and PRM.Short description of practice: We have implemented a program to improve drug treatments in our patients, through pharmacist’s interventions derived from medication reviews and prescription validation.The program has been established in two heath systems, managed by our Group:- Long term care and subacute care Hospitals (HSS): HSS Mutuam Güell (165 beds) and HSS Mutuam Girona (103 beds).- Health care support teams for nursing homes: EARs (Formed by physicians and nurses)In the two Hospitals, pharmacists’ can make interventions at different moments of the patient process: Admission, during the hospital stay and at discharge. In EARs, pharmacists make at the admission of the patient in the nursing home.Drug related problems detected are communicated to the physician through email or telephone. Drug related problems are recorded in a database using Microsoft Excel® using the ASHP (American Society Health-System Pharmacists) classification, as well as answers or lack of it from physicians.Improvement in drug treatments is evaluated using the MAI (Medication Appropriateness Index)Key findings: Period considered: June 2014-2015Demographic data: Mean age HSS 80.7 years (70% female) and EARs 84.8 years (59% female). In both cases more of the 69% of patients taking ≥ 9 drugs.Total of treatments reviewed by pharmacists: 3671 in EARs and 2176 in HSS.Have been conducted 4115 interventions in EARs (1.94 interventions/patient) and 2534 in HSS (2.43 interventions/patient). The degree of answer was 44% in EARs and 79% in HSS. Of the interventions/recommendations answered they were accepted in an 84 % (EARs) and 72% (HSS).More frequent PRM found where similar in HSS and EAR: Inappropriate dose, dosage form, schedule, route of administration, or method of administration; Medication with no indication: Condition for which no medication is prescribed and Problems are arising from the financial impact of therapyMAI values after implementation by physicians of pharmacist’s recommendations in EARs decreased from 4, 4 to 2.68 (p< 0.0001); in the HSS values decreased from 3.75 to 1.74 (p

In the framework of the Quality Improvement Plan, a multidisciplinary working group on drug use improvement was created. The group was formed by three physicians from different specialities, two nurses, a pharmacist, a pharmacy technician and the coordinator of quality and patient safety. The work of the group was focused on improving the use of high risk medications in the hospital setting. The implementation of some of the improvements through the computerised physician order entry system was also considered. In the first 18 months of work, the group, in collaboration with other professionals and diverse departments of the hospital, implemented several improvements in drug safety: maxim dose alerts in electronic prescription, standardisation of dilution and dosages for intravenous high risk drugs, use of premixed solutions of potassium chloride, insulin protocols for electronic prescription in medical and surgical patients and emergency drug guidelines. The group has been extremely efficient in putting into practice protocols, procedures and guidelines for high risk medications with consensus and in a relatively short time.

Background Optimising drug treatment is an essential part of caring for older people. Due to the comorbidity and frailty of this population, pharmacologic treatment should be individualised and reviewed to ensure the benefits for patients. The involvement of pharmacists through interventions has led to positive outcomes in different settings, although there is not a broad experience in nursing homes. Purpose To optimise pharmacotherapy through pharmaceutical interventions in geriatric patients in nursing homes within a pharmaceutical care programme. Materials and methods In the Prescription Quality Unit (PQU), two pharmacists provide training and support to several care teams in nursing homes. They review clinical reports and medication plans of patients, using an algorithm developed by the pharmacy service of our institution according to criteria of efficacy, safety, efficiency and standards in geriatrics. The problems detected and pharmaceutical interventions are communicated to the physicians in reconciliation meetings. Results A prospective study was undertaken during August and September 2013. Medication plans of 62 patients (mean age 84 years) were reviewed. 211 interventions were made with a 78% acceptance rate by physicians. These interventions were related to: Reconciliation 24% Drug omission 19% Drug not indicated 15% Drug inappropriate in geriatrics 15% Dosage error 7% Duplication 6% Contraindication 5% Low intrinsic value drugs 2% Length of treatment 1% In the 22% of the interventions not accepted, the main reasons were: specialist follow-up, the change had been already made unsuccessfully, to prioritise the stability of the patient over the recommendation. Conclusions There is a high incidence of medicines problems in nursing homes. The work of pharmacists has a high value in improving drug use in these settings. In parallel, it encourages communication and collaboration between professionals. No conflict of interest.