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Author(s)

Javier Corazón Villanueva, Natalia Sanchez-Ocaña MartínPast, Virginia Puebla García, Lidia Ybañez García, Maria De la Torre Ortíz, Paloma Pastor Vara, Maria Fernandez-Vazquez Crespo, José Manuel Martínez Sesmero

Why was it done?

The PLS is the perception of a non-existent limb that may occur in up to 80% of amputees. The management of this syndrome is complex and alternative drugs are sometimes used for the treatment. The absence of a marketed formulation, off-label use of drugs and the complex treatment of pain make the role of the pharmacist essential.

What was done?

Development and validation of an oral ketamine compound and a specific pharmaceutical care circuit (PCC) as a part of the treatment of phantom limb syndrome (PLS).

How was it done?

A literature search was carried out on the preparation of this compounding, as well as on the use of oral ketamine (bioavailability, dosage, adverse reactions).
An oral solution of 10mg/ml was prepared (final volume 50ml: 500 mg of injectable ketamine solution or raw material, 20 ml of simple syrup with a sufficient amount of purified water and 2 drops of lemon essence). To establish the expiration date recommendations of Good Manufacturing Practice Guideline were followed and the organoleptic characteristics were evaluated for quality control.

The PCC created consists of the following stages:
1. Setting up a first presential visit to provide pharmaceutical care during admission: to inform the storage conditions, most common adverse effects and recommendations about medication intake.
2. Dispensing at discharge and initially appointments every 7 days for a closer follow-up: control of adverse reactions (confusion, agitation, nausea, etc.), monitoring of the appropriate use of ketamine and other analgesic medication (avoiding possible abuse and addictive behaviour) and pain control. Pharmaceutical interventions are communicated to the pain management unit (PMU).
3. Spacing of visits fortnightly once the treatment is well-stablished and proposing a telepharmacy service.

What has been achieved?

The ketamine formulation developed has been used in our hospital in three patients with satisfactory results. The interventions carried out were: pain control problems, possible inappropriate use, reduction in the number or dosage of concomitant medication or ketamine itself.

What next?

The capacity to provide therapeutic alternatives and a more exhaustive pharmacological control of pain in collaboration with the PMU can improve the safety and effectiveness of these treatments.

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Author(s)

Ana Rita Silva, Cláudia Santos

Why was it done?

Low-risk pregnant women are also prone to suffer from minor pathological conditions, such as migraines, low back pain, gastrointestinal disorders. In view of this particularity, collaboration was requested from the pharmaceutical services to prepare a therapeutic guide to make available to all doctors in the hospital, in particular general and family medicine.

What was done?

Develop a pocket guide with OTC medicines classification in pregnant women for the following symptoms: pain control; colds; gastrointestinal changes and skin changes, according to Food and Drug Association (FDA) classification, for general and family practice physicians in the hospital.

How was it done?

It was necessary to define which pathologies/symptoms we would focus on, this choice was made in collaboration with the person responsible for the obstetrics service. Then, focusing our work on low-risk pregnant women, we selected some drugs that are prescribed to non-pregnant women for chosen pathologies/symptomatologies. These drugs were thus analysed in view of their safe use in low-risk pregnant women using tools such as the summary of drug characteristics, the FDA website, the UpToDate online platform. The guide was made available to general and family physicians.

What has been achieved?

The drug classification was compiled in a table organised by INN, divided by pathology/symptomatology, with the FDA classification and also a column with a pictogram indicating the safety of the drug for use during pregnancy. The acceptance by clinicians was very positive, reinforcing that it is important to pay special attention when prescribing in the 1st and 3rd trimester of pregnancy, use the lowest effective dose and for the shortest possible period, avoid using “new” drugs unless there are safety studies.

What next?

The next step to support clinicians will be to develop other tools to help prescribe other classes of drugs as well as another population group, such as safe drugs in breastfeeding.

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Author(s)

Claudia Elias, Alda Morgado, Daniel Amaral , Fátima Cimadeira, Nadine Ribeiro

Why was it done?

Anxiolytics, sedatives and hypnotics consumption in Portugal represents 6,1% of the drug market (1). Their prescription, which should be limited in time, 12 weeks maximum, is often prolonged. As a result, patients experience cognitive deterioration, falling risk increase and tolerance and dependence. As a result, withdrawal phenomena occur, making it difficult to stop BZD. (2) Addressing this problem at the beginning of BZD use is important, avoiding chronic use.

What was done?

An interdisciplinary team was created, involving psychologist, a clinical pharmacist and a general practitioner (GP), of Primary Health Care (PHC) for patients with insomnia or anxiety who accept to participate in the benzodiazepines (BZD) Withdrawal process.

How was it done?

In December 2021, PHC’s GP started eligible patients selection and their referral. The dose reduction schedule is selected by pharmacists and agreed with GP. During the process, psychologists help patients developing skills to overcome psychological barriers; pharmacists monitor the withdrawal process, supporting deprivation management. The interdisciplinary team is in permanent contact, favouring successful withdrawal.

What has been achieved?

Eleven patients were appointed; eight remain in follow-up. Initial prescriptions started for anxiety, insomnia and depression episodes and were continued over time. Intercurrences in personal lives and concomitant therapies changes conditioned delays in withdrawal process. On average, we managed to reduce BZD dose by 25% every 12 weeks, requiring nine pharmacist appointments. Despite difficulties, patients’ motivation and effective BZD reductions and/or ending are the desired health outcomes, suggesting the success of this intervention.

What next?

Currently, we are adjusting the method and the referral process, minimising some of the difficulties faced. We are also presenting the project to new healthcare units, as we intend to guarantee equity in access to the BZD withdrawal programme for all eligible patients.

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Author(s)

Roberto Brunoro, Mariassunta Miscio, Girolama Iadicicco, Lorenzo Codato, Domenica Condello, Elisa Danieli, Viola Donadello, Alice Osto, Federica Pace, Giulia Valente, Francesca Venturini

Why was it done?

In our Italian University Hospital, we established the “Clinical Research Helpdesk” managed by the Clinical Research Unit. According to a daily schedule all personnel with an active role in clinical research can reserve an appointment with a pharmacist and administrative staff to ask questions for the submission of the necessary documentation for the Ethics Committee (EC) and for the evaluation of the study feasibility.

What was done?

In our Italian University Hospital, we established the “Clinical Research Helpdesk” managed by the Clinical Research Unit. According to a daily schedule all personnel with an active role in clinical research can reserve an appointment with a pharmacist and administrative staff to ask question for the submission of the necessary documentation for the Ethics Committee (EC) and for the evaluation of the study feasibility

How was it done?

The schedule is a Google Calendar tool which permits to generate slots of appointments. Researchers can access it by a link spread during a presentation event of the initiative. At each appointment the presence of a pharmacist for scientific counselling and a member of the EC scientific secretariat is guaranteed.

What has been achieved?

Since March 2022 the helpdesk accounts for 120 appointments with an average of 17 appointments/month. Typical questions are related to documental forms clinical trials rules and regulation counselling; in the last period support was requested also for practical issues, e.g., CE marking for investigational medical devices, feasibility evaluation, contract agreement and informed consent. After the helpdesk activation, the processing time for all the evaluation steps from the document presentation until EC submission, decreased by 50% compared to the previous year. The service increased study submission: the requests for evaluation of interventional studies received by the helpdesk increased by 15%, whilst for observational studies the percentage increase was 10%.

What next?

We are planning to expand this service to reach a complete management of clinical trials introducing a “RedCap team”, consisting of clinical pharmacists and biostatisticians who will help researchers in study design, Clinical Research Forms (CRFs) creation, statistical evaluation and data interpretation. A legal team for legal issues and contract agreement counselling will also be offered. The aim is to increase the visibility of our hospital, making it more attractive for clinical research.

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Author(s)

Jorge Fernández-Fradejas, Matías Morín-Rodríguez, Eva Delgado-Silveira, Miguel Ángel Moreno-Pelayo, Ana María Álvarez-Díaz

Why was it done?

There is an increasing number of gene-drug interactions that have the potential to predict patient response. Although the study of some genetic variants can be a useful tool to achieve a safer and more effective pharmacotherapy, the integration of personalised medicine in clinical practice has been challenging over the years, mainly due to prescriber’s scepticism and lack of clinical guidelines and protocols.

What was done?

We have implemented a multidisciplinary Personalised Medicine Unit (PMU) at a third- level hospital to facilitate preemptive pharmacogenetic testing.

How was it done?

The PMU provides its service with the involvement of Pharmacy and Genetics Department according to the following workflow:
1. Physicians order the pharmacogenetic test in the first contact with a patient expected to be treated with a drug with an available pharmacogenetic test.
2. A peripheral blood sample is drawn for DNA extraction and analysed by the Genetics Department.
3. An integrated pharmacogenetics report is generated and uploaded to the patient’s electronic medical record. This report contains the molecular information and its interpretation (responsibility of Genetics Department) and the clinical pharmacotherapeutic recommendation according to the results obtained (responsibility of Pharmacy Department). Dose adjustment recommendations follow the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines and Dutch Pharmacogenomics Working Group (DPWG) guidelines.
4. Pharmacy Department follows up pharmacotherapeutic recommendation acceptance and clinical outcomes.

What has been achieved?

Since July 2021 we have implemented pharmacogenetic testing for seven drug-gene interactions:
July 2021. CYP2C9 – Siponimod.
November 2021. DPYD – Fluoropyrimidines (capecitabine, fluorouracil, tegafur).
April 2022. UGT1A1 – Irinotecan, liposomal pegylated irinotecan, sacituzumab govitecan.
Three hundred and seventy patients have benefited from pharmacogenetics testing. These tests have been requested by three different clinical departments and had a mean turnaround time of less than 10 days, preventing any potential treatment delays. An integrated Pharmacy-Genetics report with individualised pharmacotherapeutic recommendations was generated for every patient. These recommendations had an acceptance rate of 100%.

What next?

Since the creation of the PMU, we have been able to implement pharmacogenetic testing in clinical practice with a high level of acceptance. Our next challenges are introducing next- generation sequencing for the study of new gene-drug interactions in the unit portfolio and achieve a deeper integration of pharmacogenetic information in clinical decision support systems.

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Author(s)

Trine R. H. Andersen

Why was it done?

In Region Zealand, 1 of 5 regions in Denmark, clinical pharmacist services have been developed and implemented for the past decade. Especially in the acute wards, clinical pharmacists are an integrated part of the team when receiving, assessing and admitting patients to the hospital. As stated by the EAHP, “Clinical pharmacy services should continuously evolve to optimise patients’ outcomes” (EAHP statement 4.8), and a new approach was taken to further optimise the existing collaboration between the physicians and pharmacists on patients’ medication.

What was done?

The clinical pharmacy department of Region Zealand Hospital Pharmacy engaged a project with a senior year anthropology student. The anthropology student observed clinical pharmacists working with clinical pharmacist services in three acute wards. The observations on the collaboration of patients’ medication processes were disseminated to the pharmacists and physicians at the wards. This will aid in further strengthening of the collaboration and utilisation the healthcare professionals’ individual competencies in the hospital wards.

How was it done?

A senior year anthropology student was engaged to do objective observations of the pharmacists and physicians when collaborating in the acute wards. An anthropologist is trained to suppress subjective opinions and has no previous inception of the healthcare professionals’ work in the acute ward, and hence can do low biased observations. For 4 months the anthropologist made objective observations several times a week at each ward, and towards the end of the studies also supplemented the observations with individual interviews to further understand observed situations.

What has been achieved?

After the field observations and interviews, recurrent observation points were extracted from data and presented to the pharmacist and physicians in plenum. Discussions on the presented observations was found enlightening and strengthened the teamwork by better understanding the differences in the pharmacists’ and physicians’ responsibilities in the medication process respectively. Take home messages were visibility as well as accessibility of the pharmacist, and respect of each other’s contributions to the team.

What next?

The data will further be analysed and processed during the anthropology student’s final year and master’s thesis. The take home messages will be combined in a short introduction leaflet aimed for newly employed clinical pharmacists.

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Author(s)

Aina Oliver Noguera, Luis Pérez de Amezaga Tomáss, Margarita Nigorra Caro, Fernando Do Pazo Oubiña, Esther Falcó Ferrer, Teresa Fernández Rodriguez, Maria Fiorella Sarubbo, Antònia Obrador de Hevia, Montserrat Vilanova Boltó

Why was it done?

Treatment with fluoropyrimidine produces severe toxicity in about 30% of the patients. This toxicity has been related to a reduction in the activity of DPD, the rate-limiting enzyme for fluoropyrimidine catabolism. This is due to certain genetic variants of DPYD, the gene encoding DPD. For this reason, regulatory agencies such as the European Medicines Agency (EMA) recommend determining DPD deficiency in all patients who are candidates for treatment with fluoropyrimidines.

What was done?

Design of a protocol for the Implementation of dihydropyrimidine dehydrogenase (DPD) genotype tests in our hospital so that the results can be clinically interpreted by the pharmacists, and then used to guide physicians in the dosing of fluoropyrimidines (5-fluorouracil/capecitabine). The project was done with the collaboration of the Genetic and Genomic Laboratory (GGL) located in the reference hospital of our territory.

How was it done?

The elaboration of the protocol took place as follows, coordinated by the oncology pharmacist:
– Informatics. They created a formulary at the electronic prescription programme (HP-HCIS®) for the inclusion of the patients in the testing protocol.
– Oncologists and nursing service. They were trained in the implementation of this new determination, as well as in the procedure for obtaining and sending samples to the GGL.
– GGL. They conducted the DPYD genotype tests and report the results to the oncology pharmacist.
– Oncology pharmacist. They did the clinical interpretation of the result based on the following European Society for Medical Oncology (ESMO) recommendations for heterozygous DPYD variant allele carriers:
-DPYD*2A (rs3918290): dose reduction of 50%
-c.1679T>G (rs55886062): 50%
-c.2846A>T (rs67376798): 25%
-c.1236G>A/HapB3 (rs56038477): 25%

What has been achieved?

Since the implementation of the protocol, 73 determinations of DPYD polymorphisms have been performed (November 202 to August 2022). Three patients (4.1%) were found to be heterozygous DPYD gene variant carriers (two DPYD*2A and one c.2846A>T).
The average time for obtaining the results was 17.5 days. For this reason, in most cases the treatment was started before the result was obtained.

What next?

We are working on the implementation of a new fluorescence technique that will allow us to shorten the time of obtaining the genotype result.

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Author(s)

Cathrine Noergaard Peulicke, Michelle Lyndgaard Nielsen

Why was it done?

The process of building a new hospital has led to development and rethinking the drug concept. At the hospital we always have “the patient first” in mind. This is our codex. That is why we are changing the concept for delivery, dispensing and administration of medication. We wanted to ensure that the concept functioned from a patient safety perspective, patient flow perspective, patient involvement perspective, professional development perspective and perspective of a healthy operation. The vision is the right medication, from the right hand at the right time.

What was done?

At the new hospital, the medication logistics will undergo major changes. There will only be medication for acute use at the wards, the rest will be delivered ready-to-use from the main pharmacy or from a decentralised unit, called Pharmaservice. Here IV-solutions with short expiration are being reconstituted and oral solutions are dosed according to the prescription. Tablets and capsules are dispensed in the multi-dose robot at the main pharmacy. The multi-dose medication is equipped with a bar code which is scanned at administration and full electronic documentation is obtained. The majority of the medication will be dispensed daily for 24 hours and delivered in boxes for each patient to the wards.
In order to ease the transformation, we have built a mock up of a Pharmaservice unit where this set-up is enrolled to all inpatient wards in the hospital on the geriatric ward, children’s ward and gynaecology and obstetrics ward.

How was it done?

A steering group was founded and membered by managers from the involved wards including the hospital Pharmacy. Frequent meetings with the involved wards has been necessary to ensure competences and communication. Post-implementation we are closely evaluating the initiative.

What has been achieved?

Patient safety is in focus and with the multi-dose dispensing robot we have achieved full electronic documentation from the prescription, dispensing and administration process, and thereby have reached closed loop medication.

What next?

Having implemented the initiative on three wards, we are now working on enrolling this to the entire new hospital when it is ready in 2024. At the new hospital, we will have five Pharmaservice units servicing all inpatient wards.

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Author(s)

Rik Stuurman, Sofie Hessels, Chantal Kats, Chantal van Egmond, Kim Gombert-Handoko

Why was it done?

The administration of intravenous medication directly into the drip chamber has several benefits: 1) it saves time during preparation and administration for the nursing staff, 2) the patient has a shorter and controlled administration of the medication, often with less fluid and 3) the reduction of the use of infusion bags is sustainable and reduces costs.

What was done?

Administration of intravenous medication into the drip chamber using the integrated needle-free injection adapter is a good alternative to bolus injections and parenteral infusion. We conducted two pilot experiments at four wards, where we injected the 30 most frequently administered medications directly into the drip chamber instead of using an additional infusion bag via a sideline, which is the common practice in our hospital.

How was it done?

For the most frequently administered medications, we assessed whether it was possible to inject directly into the drip chamber. For these medications, we also defined the pump speed and the volume to rinse the system after each infusion. This information is explicitly described in our local parenteral handbook. In addition the nursing staff was fully trained and the procedures were updated.

What has been achieved?

During the evaluation of the first pilot after three months of the implementation, about 90% of the nurses indicated that they were satisfied with this alternative way of administration, that they did not experience any problems during the procedure and that they saved time compared to the old method. The second pilot will also evaluate the real-world reduction in infusion bags and costs (results are expected in December).

What next?

This alternative way of administration is now fully implemented and will be rolled out over the other wards with a “starter package”, which includes a guide for implementation, training material and frequently asked questions. In addition, the method will be fully integrated into the local parenteral handbook and the list of medications will be expanded.

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Author(s)

Dorian Protzenko, Vincent Hoang, Guillaume Hache

Why was it done?

We unveiled during an audit that, in the past 2 years, 19% of our hospital DAOCs prescriptions were underdosed: due to the population profile (old, frail), the conventional bleeding risk scores were consistently high and, as such, not informative. To avoid a hypothetical bleeding risk, physicians were randomly underdosing patients beyond guidelines, without any evidence regarding the efficacy.

What was done?

Using machine learning, we unveiled that underdosing direct oral anticoagulants [DAOCs] to prevent bleeding risk in an old and frail population had no significant impact on drug-related hospitalization [DRH] nor death, and cannot be supported. To help targeting patients for whom extra care would be more beneficial rather than underdosed DAOCs, we built a predictive model of bleeding events and provided risk factors among our population.

How was it done?

We performed a retrospective study, based on data collected during the audit, of patients treated between October 2020 and April 2022 with Apixaban or Rivaroxaban for atrial fibrillation [AF]. Demographic and clinical criterias (i.e., GFR, polypathology, co-medications, prescribed DAOC, respecting dosage and scheduling) were collected. The occurrence of specific outcomes (i.e., bleeding and thrombosis that led to medical care and drug seizure, DRH and death) were retrieved from the patients’ medical records. Machine learning explorations were performed using RStudio®.

What has been achieved?

119 patients were included. We modeled using logistic regression the impact on selected outcomes of underdosing DAOCs. We found out that underdosed DAOCs were associated with a lower bleeding risk (OR=0.30, CI95%[0.07;0.95]), a higher thrombosis risk (OR=6.67, CI95%[1.23;50.0]), but without any impact on DRH nor death. Unsupervised algorithms unveiled that DAOC choice (Rivaroxaban: OR=2.80, CI95%[1.15;7.13]), sex (Male: OR=0.44, IC95%[0.16;1.12]) and using dosages from guidelines (OR=3.32, CI95% [1.05;14.80]) were predominant explanatory variables regarding bleeding risk. The choice of DAOC was the only covariate that impacted DRH (Rivaroxaban: OR=2.78, CI95%[1.22;6.56]). Finally, using a gradient-boosting algorithm, bleeding risk was predicted with a 0.73 roc-auc, superior to conventional models.

What next?

Therapeutic education of patients and caregivers, telephone follow-up or pharmaceutical consultations will be implanted for patients at high bleeding risk. An audit will be performed next year to measure underdosed prescriptions rate, and improve the model with new data.