Author(s)

Wei Wang, Hao Bai

Why was it done?

It depend on the pharmacokinetic (PK)/pharmacodynamic (PD) of vancomycin. Vancomycin can be described as a kinetic model with one compartment connected by a series of first-order kinetic rate processes. The mini programme uses two drug levels during the same dosing interval by the TDM to calculate the area under the curve (AUC) of vancomycin and integrated into patients’ condition and minimal inhibitory concentration of pathogen to provide an optimal dosing regimen of vancomycin.

What was done?

We designed and developed a mini programme support for personalised therapeutic drug monitoring (TDM) of vancomycin. This programme can be easily used in the WeChat by the mobile device.

How was it done?

The traditional vancomycin TDM strategy, which is guided by trough concentrations, has several limitations:
The recommended trough concentration range of 10-15mg/L assumes that the bacteria’s minimum inhibitory concentration (MIC) for vancomycin is ≤1mg/L. However, with the drifting of vancomycin’s MIC values over recent years, this trough concentration has not been able to effectively guide patient prognosis, as has been confirmed by many clinical studies.
There are practical difficulties: for example, the 2009 IDSA guidelines clearly specify that the trough concentration of vancomycin should be sampled half an hour before the fifth dose. However, in reality, due to misunderstandings by nursing staff or excessive workload, sampling times often deviate from this guideline.
After the trough concentration has been determined, there are no explicit measures for dose adjustment. The 2009 IDSA guidelines do not provide recommendations on how to adjust subsequent doses based on trough concentrations.
A decade later, in 2020, the IDSA released new vancomycin TDM guidelines. These guidelines suggest moving away from the trough concentration TDM strategy for vancomycin, and instead recommend using an AUC-guided strategy, determined by two-point blood concentration monitoring of vancomycin.

What has been achieved?

Vancomycin follows first-order pharmacokinetics. To monitor the AUC of vancomycin, it is necessary to measure the serum vancomycin concentration at two steady-state points, then use Monte Carlo simulations and Bayesian software to calculate the AUC and adjust the dosage. This process requires a large number of calculations. Therefore, there is an urgent need for an auxiliary decision making system in clinical practice that can facilitate personalised dosing of vancomycin.

What next?

This mini programme has run above 1 year, providing personalised medicine service of vancomycin to hundreds of patients in China, guiding the precise and rational use of antimicrobial drugs , enhancing the effectiveness of vancomycin and reducing drug toxicity in clinical practice.

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Author(s)

ROSA MARIA ROMERO JIMENEZ, VICENTE ESCUDERO VILAPLANA, ESTHER CHAMORRO DE VEGA, MARIA FERRIS VILLANUEVA, ELENA LOBATO MATILLA, DANIEL GOMEZ COSTAS, JUAN VICENTE VALOR, ANA HERRANZ ALONSO, MARIA SANJURJO SAEZ

Why was it done?

BT for patients with IMID have increased the effectiveness, but also with adverse events (AE) or problems in their administration. In addition, patients have greater formation and communication needs. We wanted to develop an app to improve communication and monitoring of these patients.

What was done?

In 2020, we developed a mobile application (app) to improve communication and monitoring of Immune-mediated inflammatory diseases (IMID) patients treated with biological therapies (BT). We implemented the app in December 2020.

How was it done?

A multidisciplinary group composed of pharmacists, dermatologists, rheumatologists, gastroenterologists, and nurses designed an app for IMID patients in a tertiary hospital. The app consists of the following modules: Medication, Questionnaires, Adverse Events (AE), Useful Information, Messages, and Patient Profile. We offered the app to IMID patients who initiated a new BT. We performed an observational, longitudinal study to assess the app’s impact on medication adherence, safety, and communication. The inclusion period was from December 2020 to August 2022. The inclusion criteria were age ≥ 18 years, diagnosis of an IMID, and ownership of a Smartphone. Patients with language barriers were excluded.

What has been achieved?

380 patients were included (mean age: 43.6 years [SD=13.9] and 58.3% were female). Concerning the type of IMID, 61.1% of patients had a rheumatologist disease, 26.3% a dermatologist disease, and 12.6% a gastrointestinal disease. The mean follow-up time for app use was 20.5 (14.5) months. In the Medication module, 100% of patients registered their biological therapy and 51.1% also used this module to record each dose of medication administered. 85.3% of patients had adherence >90%. A total of 433 AE were registered. 31.3% of patients registered at least 1 AE. The most frequent AEs were fatigue (32.1%), injection site reaction (15.2%), headache (11.8%), and diarrhoea (8.3%). 53% of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (29.8%), logistical and citation issues (20.8%), and drug interactions (17.9%).

What next?

The next steps will be that the app can be used in other hospitals in our country and also adapt the app to be used in other pathologies.

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Author(s)

Marta Anghilieri, Francesco Guidoni, Vito Ladisa

Why was it done?

The new DNA sequencing techniques, globally defined “Next Generation Sequencing (NGS)”, allow the parallel sequencing of many samples producing in short times a big amount of data. To enable comprehensive analysis of the data and develop new specific and clinically useful therapies, we have introduced the approach of evaluating the data by the MTB, which includes pharmacists as experts in drugs and their use.

What was done?

Hospital Pharmacists (HPs) are integrated into the Molecular Tumour Board (MTB), a multidisciplinary group, to select the most appropriated therapy for oncology patients, ensure and facilitate patient access, and demonstrate therapeutic appropriateness found by MTB analisys.

How was it done?

MTB members, including HPs, perform DNA sequencing on each patient using NGS to identify known/unknown alterations. These data are entered into a database available to all MTB members and are the basic tool for selecting potential target therapy. The MTB meets once a week to discuss and integrate the observed DNA alterations with the patient’s clinical history. In this way, the most appropriate target therapy for the patient can ultimately be selected. The HPs then provide the patient with access to medications.

What has been achieved?

In this study, 208 patients affected by Non-Small Cell Lung Cancer were evaluated. DNA sequencing of patients identify 117 altered genes. After an extensive literature search, 15 genes were highlighted as potential targets for available drugs. They marked 116 patients potentially tractable with target therapy, of which 47 patients were candidates to a target therapy already in clinical practice and 69 to a target therapy not in clinical practice. Comparing the two groups, among candidates for drugs in clinical practice, treatment was started in 65% and continued in 53%; among those treated with drugs not in clinical practice, treatment was started in 23% and continued in 69%.

What next?

The inclusion of HPs in MTB allows for more deliberate use and better selection of drugs. HPs provide valid support to select drugs and facilitate access to them: HPs individualise the applicable therapy for a larger number of patients through MTB, they analyse the therapeutic outcome (MTB-selected therapy has a bigger chance to last longer) and the cost impact on the NHS.

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Author(s)

Florian Poncelet, Cedric Mwamba, Valentine Foulon , Anne-sophie Da Silva Rego, Catherine Floret

Why was it done?

Medication adherence of post-stroke treatments is important in preventing stroke recurrence. Problems of adherence with these medications are frequently encountered. Patient education is therefore essential in the management of this pathology.

What was done?

The creation of tools for the medication session of the post-stroke therapeutic education programme and the measure of the activity impact on patients’ knowledge of their treatments.

How was it done?

The session is led by a pharmacist in the form of a Game of the Goose, with the cards divided into 3 different colours, each corresponding to one of the 3 categories seen during the activity: General Questions, Statins and Anticoagulants/Anti-aggregants. This form allows participants to learn in a fun way and to promote interactions.
To evaluate the impact of these sessions, the same quiz is filled out by the patients at the beginning and end of the session, in order to measure the improvement of their knowledge. This quiz is in the form of an evaluation grid, composed of 20 questions with binary answers (True/False) covering the concepts discussed during the activity. The answers allow the attribution of a grade out of 20.

What has been achieved?

33 game cards were created (12 cards for general questions, 8 for statins and 13 for anticoagulants/anti-aggregants, of which three concern anti-vitamin K).
The patients take turns drawing a card and think collectively. The correct answer is later explained by the pharmacist. At the end of the activity, forms summarising the points discussed are given to the patients.
Concerning the quiz, the evaluation of the impact of these sessions was carried out on a first group of seven patients. The average score was 14 (12-17) at the beginning of the activity and 17 at the end (15-20), thus an average improvement in knowledge of 21% (0-58%).

What next?

An analysis of the questions with the lowest rate of positive responses will help us to improve the messages during the activity. A treatment plan given to patients at the end of the session to help them take their medication is also being discussed.

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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)

Sabrina Trivellato, Daniele Mengato, Maria Mazzitelli, Anna Maria Cattelan, Francesca Venturini

Why was it done?

An optimal compliance is an essential requirement for people living with HIV (PLWHA) to grant drugs effectiveness and safety. Given the complexity of the therapeutic regimen, and the multiple changes to it due to the clinical status, compliance to therapy may be suboptimal. Patients who are not well educated on how to follow their therapy are more keen on quitting the treatment or facing virological failure. According to previous analysis, we reported that 120 patients out of more than 1500 managed by our centre experienced suboptimal adherence to therapy.

What was done?

We created a user-friendly tool to educate HIV-patients on their drugs’ adherence in our University Hospital.

How was it done?

We studied every drug prescribed in our centre and we analysed it from the patient’s point of view. The question we aimed to answer was: “If I were a PLWHA, what would help me assuming the correct drug, at the proper time, avoiding misunderstandings?”. We analysed the shape, colour and dimensions of both the package and the pills/capsules. We focused on the most appropriate way to take every drug and we investigated possible interactions with OTC drugs or dietary supplements.

What has been achieved?

A poster reporting all the drugs available in our formulary was developed: 34 medicines were described in alphabetical order, specifying for each one the image of the package, the usual dosage, the picture of the pill/capsule compared to the dimension of current coins and special warnings about possible drug-drug interactions. We also adopted practical symbols to indicate whether to assume the drug with or without food. The poster became available starting from April 2022 and during the following 5 months a cohort of 960 patients could rely on it.

What next?

In order to help our patients taking their therapies, we expect to get a digital form of this poster to make it available on the phone scanning a QR code. Alongside, we aim to enlarge and improve this digital version by adding a final section with an interactive survey to closely monitor the compliance of the patients and help them to improve it. Through this project we could also obtain an active pharmacovigilance setting.

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Author(s)

Vera Pires, Maria Teixeira, António Gouveia

Why was it done?

Cisplatin is a cytotoxic agent used in CT regimens in ST. (1) Nephrotoxicity is the main toxicity, and hydration is always indicated to prevent kidney damage. [1,2] In 2018, when we computerized the ST’s CT protocols, we verified the existence of variations in CH protocols. According to the bibliography, this lack of standardization could lead to sub-optimal treatment of patients, errors and unnecessary use of resources. [1,3] Thus, it was necessary to develop a standardized hydration protocol designed by pharmacists with the collaboration of oncologists.

What was done?

Standardize the cisplatin-based hydration (CH) protocols used in the solid tumors (ST) chemotherapy (CT) regimens in adults in our institution.

How was it done?

Audit of CH protocols used in ST in adults in our institution and literature review to build a standardized evidence-based protocol.

What has been achieved?

We gathered 31 CT regimens with cisplatin. Verified the existence of variations in the volume of hydration (VH) before and after cisplatin, in the volumes of drug dilution, perfusion time, in the use of oral hydration (OH) and in ionic supplementation. We found that all of them were indicated to perform cisplatin only “if urine output >100ml/min”, use of mannitol before cisplatin and furosemide in SOS. Through the consulted bibliography, 4 regimens were made and implemented in 2019, according to the dosage of cisplatin: HC1< 40mg/m2 (Hday) and HC21000ml, and mannitol is only administered if cisplatin ≥60 mg/m2 (RCM). All protocols have magnesium and potassium supplementation.

What next?

Thus, despite the lack of consensus in the bibliography, a standardized protocol was created based on the evidence and clinical practice of our Institution. It is our intention to assess the impact of this intervention, from the perspective of the patient and the Institution.

Author(s)

Mapi Fleury, Januska De Maria-Lee, Alessandra Taiana, Yvan Bourgeois, Sophie Voruz, Olivier Spertini, Pierre-Yves Bochud

Why was it done?

In 2019, procedural changes within unit treating malignant haemopathies raised awareness about unsatisfactory management of NV, particularly CINV. We identified a lack of departmental consensus, leading to heterogeneous therapeutic practices, confusion over the aetiologies of NV and feelings of powerlessness among healthcare professionals. We decided to improve the whole process, from prophylaxis to treatment, by addressing specific knowledge gaps concerning CINV, improving pathophysiological and pharmacological knowledge, and implementing interprofessional management and MASCC/ESMO guidelines.

What was done?

Patient nausea and vomiting (NV)—particularly chemotherapy-induced NV (CINV) in malignant haemopathies—was managed by an interprofessional team.

How was it done?

A multidisciplinary working group was established to create a comprehensive, patient-centred NV management programme. Work sessions focussed on attaining a therapeutic consensus and adapting international guidelines to our context. Different professions learnt about each other’s needs and fields of competency, enabling each to be heard and creating mutual benefits through sharing expertise and knowledge. Pathophysiological/pharmacological leadership was given to clinical pharmacist, including developing and teaching specific protocols and supervising complex clinical situations in the field.

What has been achieved?

Interprofessional consensus was reached, documentation and techniques were implemented including clinical evaluation checklists at patient admission. CINV therapeutic regimens were completely updated and immediately and automatically included in cancer treatment protocols. The clinical pharmacist and specialist nurses give initial interprofessional training to new colleagues and ensure continuous on-site supervision. This transversal work has resulted in fewer patients suffering from NV and better team understanding of pathophysiological mechanisms, differential diagnoses and adverse drug effects—this also ended the use of unsuitable medications and dosages. Overcoming this critical situation also allowed us to begin non-pharmacological integrative care.

What next?

Interprofessional working group proved indispensable to this approach. Including CINV pharmacotherapy directly into cancer treatment plans is one of programme’s strong points and contributes to high adherence to guidelines. Team feels more relaxed and more in control. Monitoring is now done by tracking files and oral feedback, but we aim to implement systematic follow-up of interventions, care evaluations and NV to assess programme’s impact. Next stage will also include patient feedback.

Author(s)

Petra Rozsívalová, Věra Zdanovcová, Lenka Beková, Martina Maříková, Marcela Heislerová, Vladimír Koblížek, Petr Šmahel

Why was it done?

By implementing systematic monitoring in our institution, CPs ensure appropriate and safe use of unlicensed treatment available under Emergency Use Authorisation. The secondary goal is mandatory data input to national register and patient clinical outcome feedback to physicians and hospital management.

What was done?

It is vital to bring focus on appropriate use of COVID-19 monoclonal antibodies (mAbs) in high-risk population when safety and efficacy data are scarce. A team of clinical pharmacists (CPs) helped to set up process flow, monitor prescribing of mAbs and provide systematic follow-up on time course of symptoms reported by SARS-COV-2 positive outpatients since March 2021.

How was it done?

Ethics committee approval was obtained for monitoring of patients. Consented patient data are extracted from electronic prescribing system and patients score subjective symptoms using questionnaire on days 7, 29 and 90 after the infusion. The prescriber, indication criteria, infusion application day with regards to PCR positivity and symptom onset and vaccination status are recorded.

What has been achieved?

Currently our small dataset includes 59 bamlanivimab and 63 casirivimab/imdevimab patients. On average, mAbs are administered within 2 days of positive PCR test and 5 days of COVID-19 symptoms onset. Our patients report subjective improvement in symptoms by 7 days post infusion. None of our patients clinically deteriorated because of COVID-19. 100 % of mAbs administered are reported in the national database. In October 2021 we achieved that laboratory confirmed positive patients receive text message with infectionist contact to discuss eligibility for mAbs on 24/7 basis. CPs also implemented information leaflets on mAbs for patients with chronic conditions.

What next?

To date, there are no published descriptive data on real-life utilisation of COVID-19 mAbs in terms of patient characteristics, disease outcome and vaccination status. Our initiative shows na excellent opportunity for CPs to enhance timely and rational mAbs use.

Author(s)

Paola Minghetti, Giuseppe Danilo Norata, Francesca Selmin, Paolo Rocco, Vito Ladisa, Margherita Galassi

Why was it done?

The availability of mAbs to treat different pathologies is steadily growing, causing a steep increase in the level of training needed in different areas of pharmacists’ intervention, including compounding, handling and storage. As this process will be sustained by the increasing availability of biosimilars, pharmacists, the key health professionals responsible for their compounding and handling, will face new challenges.
The aim of this project is to overcome the common problems encountered by hospital pharmacists in obtaining education on biosimilars, included limited financial support, heavy workload or inadequate educational resources.

What was done?

A self-paced educational course has been designed and implemented with the aim of providing a fundamental grounding in the physical chemistry, pharmacology and technology of monoclonal antibodies (mAbs)-based medicines in oncology, both originators and biosimilars and the methodology associated with their compounding and handling.
The primary target audience for this project consists of hospital pharmacists in the EU, though students in the specialization in Hospital Pharmacy and community pharmacists may benefit from the course.

How was it done?

The course has been designed and developed to address, previously assessed, unmet educational needs. The resulting format comprises both theoretical and remote real-world training on the pharmacology, technology and stability of mAbs, the technology and rationale of biosimilars and the regulatory aspects of biotechnological medicinal products.

What has been achieved?

A series of webinars in on demand movie format has been produced. The webinars contain a comprehensive theoretical section – covering biosimilar mAbs pharmacology and formulative and regulatory aspects – and a practice section in which the preparation steps of oncology mAbs are filmed and discussed in a hospital setting. All training activities have been recorded in remote both in Italian and in English. Every module is designed to be used as a single unit and has a duration of approximately 30 minutes. The total duration of the course is 8 hours.

What next?

The course will be CME accredited in Italy through Fondazione Francesco Cannavò, nonprofit CME provider of the Federation of Italian Pharmacists Associations. It will be made available to pharmacists through national and international CME platforms, providing fundamental grounding in the methodology associated with oncology monoclonal antibody biosimilar formulation.