Literature review of pharmacogenomics in pediatric oncology patients related to chemotherapy-induced toxicity Abstract Background: As children are expected to live long after their treatment of cancer, it is important to reduce the risk of toxicities. Chemotherapy-induced toxicities can result in interruption or discontinuation of treatment, and the variability in toxicities among pediatric patients can be explained by inter-individual variability in pharmacodynamics and pharmacokinetics. Part of this variability can be explained by genetic variations. By establishing an individualized treatment in pediatric oncology, the risk of chemotherapy-induced toxicities can be reduced.  Aim: The aim of the project is to map positive and negative associations between genetic variations and the various chemotherapy-induced toxicities that affect pediatric oncology patients. Method: This literature search was performed by using Embase, Web of Science and PubMed. The articles that were included are those that describe an association between one or more genetic variations and side effects caused of chemotherapy in children between 0-18 years with a cancer diagnosis. Only articles written in English were included. Results: Only articles published 2021 were included. Eleven out of 26 articles were included where associations between different genetic variants and the risk of developing anthracycline-induced cardiotoxicity, myelosuppression, hepatotoxicity, mucositis, ototoxicity, and vincristine-induced peripheral neurotoxicity were identified. Conclusions: The results of this literature review indicate that there are several gene polymorphisms that have the potential to be used to predict the risk of developing chemotherapy-induced toxicity in pediatric oncology patients. Although some studies may observe significant evidence between some toxicity and gene polymorphism, further studies are required to achieve better validation before any guidelines can be established.

Quality of drug use in asthma Background: The National Airway Register is a quality register, which provides opportunities for quality follow-up and improvement. It contains data on individuals with asthma disease, their drug treatment and outcomes obtained in health care.  Aim: To examine how representative data on drug treatment contained in the National Airway Register are for adult patients with asthma in Region Stockholm and Sweden, respectively. Methods: A cross-sectional study based on data from the National Airway Register and the Prescribed Drug Register, where the study population consisted of asthma patients aged 18-44. Open data from the Prescribed Drug Register was limited to 15–44-year-old patients. Data were collected for the period 2016–2020 regarding drugs within ATC code R03 and dupilumab with ATC code D11AH05.  Results: A difference in the use of asthma drugs between the National Airway Register and Prescribed Drug Register with the same trend for all studied years was seen. In the National Airway Register, the proportion of individuals who used bronchodilators without having obtained any ICS was lower and a higher proportion (74-82% vs 65-70%) had obtained ICS. Drugs administered in clinics cannot be studied in the Prescribed Drug Register. Conclusions: Drug treatment in the National Airway Register generally seems to comply better with international guidelines than in the Prescribed Drug Register, which may be an indication that the quality of asthma treatment is higher for patients registered in the National Airway Register. This causes problems in generalizability since obtained data only correspond to individuals who are selected.

Pharmaceutical services in pharmacies from the pharmacist’s perspective- with focus on inhalation check  Background: Wrong use of drugs is a major problem today. Pharmaceutical services can be a solution to this problem. By ensuring that the patient receives sufficient information to be able to use his/her drugs in the right way. Developments in performing new pharmaceutical services at Swedish pharmacies are currently under investigation. Previous studies showed that pharmacists have a major impact on the development of pharmaceutical services.  Aim: The aim is to investigate the attitude of community pharmacists to perform pharmaceutical services in pharmacies with focus on the service of inhalation check.   Method: A qualitative semi-structured interview was conducted in this study among 9 pharmacists who work at community pharmacies. The interviews took place at 7 different pharmacies in the Stockholm area.  Results: The results showed that pharmacists who participated in the study have a positive attitude towards the introduction of the inhalation check service in pharmacies. The inhalation check service is considered a service that can contribute to reducing incorrect inhalation technique and optimal treatment. Prerequisites for being able to implement the service in pharmacies from the participant’s perspective are more employees, more time, a suitable place, and some type of financial compensation.  Conclusion: Pharmaceutical services provide an opportunity for pharmacies to show their usefulness in society, while at the same time providing an opportunity for pharmacists to utilize their expertise. The inhalation check service is a service needed in a Swedish pharmacy. To be able to perform the service at Swedish pharmacies, different conditions are required.

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No description available.

Background: Uppsala University Hospital Sweden is planning to implement a closed loop medication system, with the aim of reducing risk prescriptions from the point of drugs being prescribed to orders being produced and administered. With inspiration from Leuven, an advanced system for pharmaceutical validation; System Assisted Pharmaceutical VALidation (SAPVAL) is planned to be developed. Aim: The aim of the study was to obtain a deeper understanding of clinical rules as an important element for building the SAPVAL system. This study will review and further develop a first set of clinical rules and validate these on the intended study population.  Methods: A retrospective cross-sectional study was performed to validate the clinical rules on a study population of 500 patients who were discharged from Uppsala University Hospital between May to July 2020. The clinical rules were applied cross-sectionally based on patient data from the electronic health records. From the total generated alerts, 10 % was randomly selected for assessment of the clinical relevance. Results: The clinical rules generated 893 alerts in 500 patients, of which 84 % alerts still remained two days after the patient was admitted to the hospital or at discharge. From the randomly selected alerts, 26 % were deemed clinically relevant. Conclusions: The developed clinical rules generate a large number of alerts for risk prescriptions for inpatients at Uppsala University hospital. The majority of the alerts remained during the care period and approximately a quarter of them were considered to be clinically relevant to remedy.

Background: Drugs are an important part of treating diseases but can also come with its risks. To reduce the risks, a system assisted pharmaceutical validation (SAPVAL) is being developed at Uppsala University Hospital. This will include the generation of alerts regarding different risks, sent to a clinical pharmacist who assesses whether the alerts should be forwarded to a physician or not. One of the risks included is QT prolongation, a relatively uncommon condition which however can result in sudden cardiac death. Aim: The aim was to map the management and the consequences of QT-related risk prescriptions and to determine the clinical relevance of QT-related alerts. Method: A retrospective cross-sectional study was performed at Uppsala University Hospital. It included the review of patients´ electronic health records (EHR) and determination of risk periods. The clinical relevance of the alerts was assessed by a physician and a developed flowchart. Results: 65 patients (age=71 ± 15 years, 54% women), and their 85 QT-related alerts were included, with a median risk period of 145 days. Within the risk period, 46 patients had an ECG taken with 35% having one or more prolonged QTc ≥ 480 ms. The risk of QT prolongation had been noticed or mitigated for 23% of the 65 patients. 89% of the alerts were concluded to be clinically relevant. Conclusion: The management and documentation of QT-related risks could be improved. It is also important to further study QT-related risk factors to better assess which patients are at the highest risk.

Bakgrund: I Sverige förekommer epilepsi hos 1-2 % av alla hundar. De första anfallen visar sig oftast när hunden är mellan ett och sex år gammal. Det nuvarande förstahands­preparatet är fenobarbital, en substans som ökar tröskeln för elektrisk stimulering av motorcortex samt minskar monosynaptisk transmission som leder till minskad neuronal retbarhet. I februari 2013 registrerades ett nytt antiepileptikum med det verksamma äm­net imepitoin. Imepitoin är en partiell agonist som binder till bensodiazepinsätet på GABAA-receptorn. Det förstärker de GABAA-receptormedierade effekterna på neuro­nen samt har en svag kalciumblockerande verkan. Syfte: Arbetets syfte var att undersöka om imepitoin har förutsättningar att bli det nya förstahandspreparatet vid behandling av idiopatisk epilepsi. Vidare var syftet att under­söka i vilken utsträckning imepitoin fungerar som antiepileptikum samt vilken biverk­ningsprofil det har. Resultat: Behandling med imepitoin gav en sänkning av antalet epileptiska anfall per månad (MSF), liknande den som erhölls vid fenobarbitalbehandling. Imepitoin sänkte MSF både som monoterapi och i kombination med fenobarbital eller kaliumbromid. Biverkningsprofilen var överlag skonsammare för imepitoin jämfört med fenobarbital. Fenobarbital visade en leverpåverkan medan imepitoin påverkade kolesterolvärdet. Slutsats: Imepitoin har en antiepileptisk effekt, liknande den som fås vid behandling med fenobarbital. Behandling med imepitoin kan ske både som mono- samt kombina­tionsterapi. Den mildare biverkningsprofilen talar för användning av imepitoin. Samti­digt har fenobarbital använts under en längre tid så biverkningar vid långtids­användning är mer välkända än de vid imepitoinanvändning. / Background: In Sweden, approximately 1-2 % of all dogs suffer from epilepsy. The first seizures often occur when the dog is between one and six years old. In Sweden the first-line drug is phenobarbital, a substance which increases the threshold of electrical stimulation in the motor cortex. It also decreases synaptic transmission which leads to decreased neuronal excitability. In February 2013 a new antiepileptic drug was regis­tered with imepitoin as active substance. Imepitoin is a partial agonist which binds to the benzodiazepine binding site at the GABAA receptor and amplifies the effects medi­ated by GABAA receptors at the neurons. Additionally, imepitoin has a weak calcium channel blocking effect. Objective: The main aim of the study was to examine if imepitoin should be the first-line drug instead of phenobarbital when treating dogs diagnosed with idiopathic epi­lepsy. A further aim was to look into which effect imepitoin had in controlling the epilepsy and which adverse effects were experienced when dogs are treated with imepitoin. Results: Treatment with imepitoin resulted in a decrease in monthly seizure frequency (MSF), similar to the decrease seen upon treatment with phenobarbital. Imepitoin was decreasing MSF both when used as monotherapy and in combination with phenobarbital or potassium bromide. The adverse effects were in general less severe with imepitoin than with phenobarbital. Treatment with phenobarbital affected the liver while treatment with imepitoin affected the cholesterol levels. Conclusion: Imepitoin has a good antiepileptic effect, similar to that of phenobarbital. Treatment with imepitoin can be used both as monotherapy and in combination with other antiepileptic drugs. Less severe adverse effects makes imepitoin a possible choice for treating idiopathic epilepsy in dogs. On the other hand, phenobarbital has been used during a long period of time and adverse effects of long term use are therefore better known than for imepitoin.

<p>Most patients are non-adherent with their medication sometimes, i.e. that they do not always use their medicines as prescribed. This might result in both under- and overuse and can lead to therapy failure, resulting in both unnecessary suffering and high costs. Therefore, medication adherence should be as high as possible. </p><p>The aims of this thesis were to investigate the refill adherence to long-term drug treatment, especially for patients with asthma and chronic obstructive pulmonary disease (COPD), and to study treatment gaps for patients with undersupply and drug costs for patients with oversupply. Further aims were to compare different methods for assessing refill adherence and analyse whether the same patient has the same refill adherence pattern to two different chronic drug treatments, i.e. diabetes and asthma/COPD. </p><p>The thesis shows that satisfactory refill adherence (80-120% of the prescribed dose) was 57% for repeat prescriptions with long-term drug treatment; undersupply was 21% and oversupply 22%. Patients with undersupply were without drugs more than half of the prescribed treatment time and the median oversupply for 90-100 days dispensation interval was 28 days. Patients who were exempt from charges had significantly higher oversupply than non-exempt patients and that leads to unnecessary cost for society. The level of satisfactory refill adherence for repeat prescriptions dispensed for asthma/COPD was on average 30%. The same low level was displayed for the elderly, where undersupply was more common than oversupply. </p><p>Assessments of refill adherence during a one-year period gave the same results irrespective of whether the repeat prescriptions were from an individual pharmacy record database or were manually collected at a pharmacy.</p><p>Patients with concomitant use of diabetes and asthma/COPD drugs do not have the same dispensation pattern for both drug types. </p><p>The introduction of patient profiles as a new approach to complement the calculated refill adherence needs to be further studied in larger and more divergent populations. In the future, the new national pharmacy record database in Sweden has opened up for larger studies and will be valuable when studying patterns of drug utilization.</p>

Most patients are non-adherent with their medication sometimes, i.e. that they do not always use their medicines as prescribed. This might result in both under- and overuse and can lead to therapy failure, resulting in both unnecessary suffering and high costs. Therefore, medication adherence should be as high as possible. The aims of this thesis were to investigate the refill adherence to long-term drug treatment, especially for patients with asthma and chronic obstructive pulmonary disease (COPD), and to study treatment gaps for patients with undersupply and drug costs for patients with oversupply. Further aims were to compare different methods for assessing refill adherence and analyse whether the same patient has the same refill adherence pattern to two different chronic drug treatments, i.e. diabetes and asthma/COPD. The thesis shows that satisfactory refill adherence (80-120% of the prescribed dose) was 57% for repeat prescriptions with long-term drug treatment; undersupply was 21% and oversupply 22%. Patients with undersupply were without drugs more than half of the prescribed treatment time and the median oversupply for 90-100 days dispensation interval was 28 days. Patients who were exempt from charges had significantly higher oversupply than non-exempt patients and that leads to unnecessary cost for society. The level of satisfactory refill adherence for repeat prescriptions dispensed for asthma/COPD was on average 30%. The same low level was displayed for the elderly, where undersupply was more common than oversupply. Assessments of refill adherence during a one-year period gave the same results irrespective of whether the repeat prescriptions were from an individual pharmacy record database or were manually collected at a pharmacy. Patients with concomitant use of diabetes and asthma/COPD drugs do not have the same dispensation pattern for both drug types. The introduction of patient profiles as a new approach to complement the calculated refill adherence needs to be further studied in larger and more divergent populations. In the future, the new national pharmacy record database in Sweden has opened up for larger studies and will be valuable when studying patterns of drug utilization.