Browsing by master's degree program "Master 's Programme in Pharmacy"

Drug-induced liver injury (DILI) is a relatively rare hepatic condition that can be classified as predictable and unpredictable. However, DILI is a primary reason for drug withdrawals, post-marketing warnings, and restrictions of use. DILI is a problem for the drug users but also for the pharmaceutical industry and regulatory bodies. From the perspective of patients' and clinicians', DILI is the major cause of acute liver injury. At present, a major problem predicting DILI in drug discovery is a poor understanding of its mechanisms as well as the complexity of DILI pathogenicity. The main mechanism behind DILI are alterations in bile acid homeostasis, oxidative stress, and mitochondrial dysfunction. More than 50 % of drugs causing DILI are causing mitochondrial impairment. If the normal function of mitochondria is disturbed, the energy production of the cell decreases, and cell function decline leading eventually to the cell death. In this study prediction of mitochondrial toxicity was studied using cryopreserved primary hepatocytes of humans and rats. The aim of the study was to clarify if there are interspecies differences in the prediction of toxicity but also investigate possible differences in the mechanisms behind hepatotoxicity by using three well-known compounds toxic to mitochondria. To determine these differences, total cellular ATP was measured after 2- and 24- hour exposure time to gain information on overall viability and possible adaptive responses. Mitochondrial energy pathways were studied as a real-time monitoring acute exposure of test compounds. Morphology, location, and possible adaptive response of mitochondria were studied using a fluorescent probe and antibody staining combined with high content imaging (HCI). Overall, primary rat hepatocytes were more sensitive to the test compounds than human hepatocytes. Also, there were differences between human hepatocyte batches that may reflect the metabolic differences between hepatocyte donors. Immunolabeling did not bring any additional values compared to the fluorescent probe staining in the study of morphology of mitochondria. Additionally, it was noticed that treatment with paraformaldehyde significantly changed the hepatocyte mitochondria morphology. Overall, more effort is needed to develop image analysis of mitochondria morphology. Finally, studying mitochondrial morphology has proven to be difficult, and this study did not unfortunately reveal any information about the adaptive responses of mitochondria for drug-induced liver injury.

Verensiirtoja tarvitaan monissa erilaisissa tilanteissa, kuten akuutissa verenhukassa, leikkauksissa ja sairauksien hoidoissa. Verivalmisteiden laajan käytön takia, on tärkeää varmistaa veriturvatoiminnalla niiden laatu sekä turvallisuus. Olennainen osa verivalmisteiden laadunvalvontaa on seuloa veren välityksellä leviäviä taudinaiheuttajia. Suomessa veren välityksellä leviävien tautien leviämisen riski on lähes olematon tarkan laadunhallinnan ansioista. Verenluovutusajankohtana oireettomat taudit aiheuttavat kuitenkin riskin laadunhallinnalle. Koska krooninen Chlamydia pneumoniae -infektio voi olla oireeton, on tärkeää tutkia taudin kykyä levitä verivalmisteiden välityksellä. Tätä ennen on kuitenkin tutkittava, löytyykö verivalmisteista edes kyseistä bakteeria. C. pneumoniae on gram-negatiivinen solunsisäinen bakteeri, joka aiheuttaa ihmisillä erilaisia akuutteja hengitystieinfektioita, kuten keuhkokuumetta, nielutulehdusta ja sinuiittiä. Vaikka suurin osa tartunnoista on oireettomia tai lieväoireisia, voi infektio muuttua hoitamattomana krooniseksi. Akuutissa infektiossa C. pneumoniae infektoi pääasiassa keuhkojen epiteelisoluja sekä alveolaarisia makrofageja. Infektion pitkittyessä bakteeri voi levitä muihin elimistön soluihin valkosolujen välityksellä. Tämä bakteerin kyky aiheuttaa kroonista infektiota sen muuttuessa persistenttiin muotoon tekee bakteerista hyvin menestyvän. Tämän tutkimuksen tavoitteena oli selvittää, kuinka paljon C. pneumoniae -bakteeria esiintyy suomalaisessa luovutusveressä. C. pneumoniae -bakteerin DNA:n tunnistamiseen kokoverestä käytettiin kolmea eri PCR-menetelmää: kvantitatiivista PCR:ää, sisäkkäistä PCR:ää ja digitaalista pisara PCR:ää. Työn ensimmäinen vaihe oli suunnitella ja optimoida nämä kolme PCR-menetelmää. Menetelmien pystyttämisen jälkeen 40 verinäytettä tutkittiin kyseisillä PCR-menetelmillä. Lisäksi samoista verinäytteistä määritettiin C. pneumoniae spesifisen vasta-aineen, immunoglobuliini G:n, määrät ELISA-immunomäärityksellä. Verinäytteitä tutkittaessa C. pneumoniae -bakteerin esiintyvyys suomalaisessa luovutusveressä oli hyvin pieni. Vain kahden näytteen (2/40) epäiltiin olevan mahdollisesti positiivisia, sillä nämä antoivat mahdollisia positiivisia tunnistuksia vähintään kahdessa PCR-ajossa. C. pneumoniae spesifisten IgG vasta-aineiden esiintyvyys oli suurempi; näytteistä 50 % oli igG positiivisia. IgG vasta-aineiden esiintyvyyden ei todettu korreloivan iän tai sukupuolen kanssa. Aiemmissa tutkimuksia C. pneumoniae -bakteerin esiintyvyys luovutusveressä on vaihdellut 7–46 %:n välillä. Bakteerin esiintyvyyden jäädessä hyvin alhaiseksi on mahdollista, että PCR-menetelmien detektioherkkyys ei riittänyt tässä tutkimuksessa tunnistamaan toistettavasti mahdollisia positiivisia näytteitä. Näin ollen PCR-menetelmien lisäoptimointi olisi tarpeen.

COVID-19 pandemic has caused a global crisis and its effects have also been reflected to pharmaceutical supply in Finland. At the beginning of the crisis the effects were especially evident in the consumption of self-medication analgesics, prescription drugs and drugs related to respiratory diseases. In a global crisis, collaboration between the public, private and third sector is becoming increasingly important, and it is important to consider how to develop the capacity for collaboration between organizations in different sectors during a pandemic. The purpose of this study was to find out how the cross-sector collaboration between the public, private and third sector of the pharmaceutical supply in Finland was organized in the crisis caused by the COVID-19 pandemic, what was the role of the cross-sector collaboration and how the preparedness and crisis management of the drug supply could be improved. The study was conducted as a semi-structured interview survey and the interviewees were selected to cover the various sectors of Finnish pharmaceutical care as well as possible. The analysis was performed by the Gioia method and thematic design. Based on the study the organization of cross-sector collaboration was both operator- and authority-oriented and the legislation and environment in the drug supply created the framework for the crisis management. Both the authorities and the advocacy organizations can be described as having acted as hubs for organization. There was no clear crisis organization in drug supply, but different actors were involved in the crisis management at different stages of the crisis. The role of collaboration was emphasized in the sharing of information and resources and in joint solution of problems. The collaboration enabled foresight and preparedness, a focus on core tasks and crisis management, and mutual benefit. Lessons learned from the COVID-19 pandemic include the need to increase and intensify collaboration, increase crisis plans and crisis training, update the system of security of supply and mandatory reserve supplies, increase self-sufficiency, and increase overall governance. Cross-sectoral collaboration was seen as useful in crisis management of the crisis in the drug supply chain. The collaboration promotes the formation of a common picture of the situation and the flow of information from the field to decision-makers. Comparing the results of this study with the literature it can be said that the results partially support the previous literature. However, crisis management of the pharmaceutical supply chain from the organization of cross-sectoral collaboration point of view has not been studied in the past.

The use of different methods of extended reality (xR) as a support in teaching has been under research for a long time. Although the use of various xR-technologies in other fields of healthcare, such as medical and nursing education, is already common, their use in pharmacy education is not yet well established. There is evidence that xR-technology has a positive impact for example on students’ motivation and learning outcomes. On the other hand, there are limiting factors that inhibit the technology becoming widespread, such as costs as well as a lack of knowledge about the technology usability. The aim of the study was to investigate usability and advantages of the augmented reality (AR) in a laboratory course as an educational supportive tool by using AR-glasses. The aim was also to investigate the learning outcomes of the students who participated in the study in three different phases: before carrying out the laboratory work (pre), immediately after the laboratory work (post) and in the course exam (delayed). Furthermore, the motivation of the students to use new technology in their studies was studied. The research was done in a collaboration with the Centre for University Teaching and Learning (HYPE) and with Sciar Company Oy. The researchers of HYPE were responsible for the pedagogical point of view, whilst the experts from the Faculty of Pharmacy were responsible for the study measurements of laboratory work related content knowledge. The research was implemented in two laboratory courses in Bachelor of Science level pharmacy studies: Medicinal product II and Pharmaceutical biology and asepsis in the fall of 2020. The students (n=18) prepared eye drops by using AR-glasses in the Medicinal product II -course and reference group (n=14) without AR-glasses. In the course of Pharmaceutical biology and asepsis, students (n=7) used AR-glasses to study the microbiological purity of the eye drops by utilizing membrane filtration method in cleanroom and reference group (n=9) without AR-glasses. ln addition, a serial dilution method was performed on a 96-well plate using an AR mobile application. The effect on learning outcomes was evaluated by using six open-ended questions measuring the understanding of content knowledge underlying the laboratory work, that were answered by the students at three different stages of the study (pre, post, delayed). To measure the usability of the AR equipment, a five-point Likert scale questionnaire studied the experimental groups students’ opinions on whether the AR mobile application could provide sufficient guidance and feedback while performing the laboratory work. In an open question, the students had the possibility to comment on the overall user experience of the AR mobile application. There were no statistically significant differences in learning outcomes between the AR-group and the reference group in both laboratory courses. The results showed indicative differences in short-term and long-term learning, with the AR-group achieving better learning outcomes in the short-term and the reference group in the long-term. In the course of Pharmaceutical biology and asepsis, the learning outcomes were the opposite. Students’ were found to be receptivity to the new technology that together with motivation supports positively the learning process. The use of AR-hardware increased certainty and reduced nervousness about the use of AR technology. As a conclusion, the study could not demonstrate the benefit of AR-technology in student learning outcomes. The study was limited by the small sample size. However, further studies are encouraged due to students’ positive attitudes and motivation towards AR technology. Regarding further studies, it is important to take into consideration the different backgrounds and learning methods of students. Thereby, the effects of xR-technologies on learning outcomes can be assessed as objectively as possible.

More and more drugs for the treatment of lung cancer are entering the market with limited research evidence and high cost. However, health care resources are limited. To provide rationale and sustainable treatment for all patients, the need for health technology assessments has increased. International value frameworks with varying uses, structures, and components have also been developed to help assess the value of drug therapies. The purpose of the study is to illustrate how physicians, authorities, and pharmaceutical industry experts define the value and the effectiveness of drug therapy. The study also aims to chart the attitudes of health care professionals towards international value assessment frameworks and to describe the current challenges in health technology assessments focusing on lung cancer therapy. In addition, the purpose of the study is to evaluate the importance of therapeutic and economic evaluation of lung cancer therapies. The research material includes interviews with physicians (n=2), authorities (n=3), and pharmaceutical industry experts (n=5). The interviews were conducted as an individual (n=8) and pair interviews (n=1). The interview method used was a semi-structured thematic interview. The interviews were analyzed by using inductive and abductive content analysis and theming. The theoretical framework in the study was related to the challenges of assessing the therapeutic and economic value of pharmacotherapies. According to the study, the value and effectiveness of drug therapy are determined in a varied and perspective-dependent manner. The value of drug therapy can be divided into three dimensions, which were therapeutic, social, and economic impact. Treatment’s effectiveness was primarily determined by the health benefits gained and by the effects the therapy has on patients, society and care pathways. Based on the data, the current challenges of the therapeutic and economic evaluation of pharmacotherapies are related to the implementation methods and criteria of evaluation and decision-making, resources, cooperation needs, scientific evidence, ethics, the structure of the health care system and legislation. Based on the results, physicians, authorities, and pharmaceutical industry experts have different opinions of the need for cooperation. The interviewees also evaluated differently the status of the current development activities and the importance of international evaluations. There were also differences in the opinions on how important the therapeutic and economic evaluation of lung cancer therapies was considered. If the importance was considered low, the importance of the evaluations was expected to increase only after the refinement of treatment recommendations and guidelines. According to the data, the international value frameworks are not actively used in Finland and their significance will be considered insignificant in the future as well. The usefulness of the value frameworks was primarily limited due to structural factors, the assessment of reliability and the current evaluation system in Finland. The benefits of the value frameworks were primarily related to the coherence of the evaluation process, easing the evaluation process and improving patient equality.

Safety of pharmacotherapies is an essential part of patient safety that promotes and supports rational use of medicines. Safety of pharmacotherapies can be divided into two areas; Drug safety and medication safety. Drug safety refers to the safety of a medicine as a product, such as the pharmacological properties and the quality of the manufacturing process. Medication safety ensures the safety of a drug therapy process preventing patients from harm during the course of using medicines. Significant inconsistencies have been identified in the terminology related to drug and medication safety. Challenges to terminology are posed by varying synonyms, ambiguity or overlap of concepts, and misclassification of events in the scientific literature. The primary objective of this study was to scope recent peer-reviewed literature related to the drug safety and medication safety terminology from the period pf 2010-2022. A secondary objective was to examine the relationship between the concepts as presented in the literature, including overlaps and differences between the terms. The study was conducted as a scoping review by using Scopus and Ovid Medline databases. The literature search covered studies from January 2010 to January 2022. The search was conducted by using the following phrases; "("medication safety" OR "drug safety" OR pharmacovigilance) W/5 (definition* OR terminology*)" in Scopus and "("medication safety" OR "drug safety" OR pharmacovigilance) ADJ/6 (definition* OR terminology*)" in Ovid Medline. The references of the included articles were reviewed for any additional material. The relevant material was selected by two researchers. A total of 71 articles were identified from the databases, of which two articles met the predefined inclusion criteria. In addition, one article was included in the study from outside the actual search. Two of the included articles were based on drug safety terminology whereas one article was based on medication safety terminology. The results revealed that there is still a considerable heterogeneity of the terms in the literature. The literature shows several terms and definitions for the same phenomenon and no noticeable consistency in the terms. It would be important to define what a uniform and systematically used terminology would require and to establish a commonly accepted guidelines for its use.

Rational, or prudent, use of medicines is one of the cornerstones of Finnish politics guiding the public procurement of medicines as a part of the medicines supply. The definition of rational use of medicines, however, takes into account the sustainability aspects of neither the drugs used nor the manufacturers behind them even though, according to One Health way of thinking, there is a connection between the sustainability of medicines and people's health. Motivated by this contradiction, the aim of the research was to map the different dimensions and usability of the corporate social responsibility (CSR) reports of pharmaceutical companies in promoting the sustainable public procurement of medicines. The values guiding the companies' sustainability actions and the impact of the COVID-19 pandemic on the companies were also researched. The materials consisted of CSR reports from years 2019-2020 of seven pharmaceutical companies that participated in public drug procurement in 2019. Two classification systems for sustainability and key performance indicators presented in previous research literature were used as a theoretical basis. Public procurement of medicines was used as a framework through which the research was carried out by using the means of qualitative content analysis. The CSR reports typically discussed the company, the environment, people, stakeholders, ethics and CSR reporting itself. CSR activities completed in the financial year in question consisted mostly of social sustainability. As for the environmental issues, emissions and climate issues played a great role. Governance-related CSR actions were the least reported and usually discussed risk management, research, and ethics. Success and pioneering, robustness and sustainability, and community spirit were recognized as themes uniting the values that guide CSR. As for in promoting sustainable public procurement, information about CSR activities, adoption of principles set by external stakeholders, CSR-related metadata, sustainability rankings, and management of sustainability in the supply chain, among other things, were found potential. The CSR reports of pharmaceutical companies contain comprehensive information about the companies’ operations, response to global trends and the values guiding the CSR activities. The use of CSR reports in public procurement of medicines necessitates further uniformity of CSR reporting practices in the pharmaceutical industry.

Tausta: Lääkehoitoon liittyvät haittatapahtumat aiheuttavat merkittävää inhimillistä kärsimystä ja taloudellista taakkaa yhteiskunnalle. Lääkitykseen liittyviä haittatapahtumia voidaan ehkäistä tunnistamalla ja puuttumalla lääkitysriskejä aiheuttaviin tekijöihin. Tavoitteet: Tutkimuksen tavoitteena oli tutkia lääkitysriskien hallintakeinoja lääkkeen toimittamisen yhteydessä suomalaisissa avohuollon apteekeissa. Tavoitteena oli selvittää, miten apteekeissa tunnistetaan ja puututaan asiakkaan lääkehoitoon liittyviin ongelmiin ja millaista lääkitysriskien hallintaan liittyvää osaamista ja lisäkoulutustarvetta apteekeissa työskentelevillä farmaseuteilla ja proviisoreilla on. Aineisto ja menetelmät: Tutkimus oli valtakunnallinen poikkileikkaustutkimus, jonka aineisto kerättiin syksyllä 2022 sähköisellä kyselyllä. Alkuperäinen kyselylomake luotiin vuonna 2015 kirjallisuuden ja järjestelmälähtöisen riskien hallinnan teorian pohjalta ja päivitettiin tätä tutkimusta varten. Tulokset: Kyselyyn vastasi 192 apteekkia (n=610). Apteekeissa tunnistettiin ja puututtiin lääkehoito-ongelmiin, mutta toimintatavat olivat harvoin systemaattisia. Yleisin puuttumistapa oli keskustelu asiakkaan kanssa ja kehotus ottaa yhteyttä lääkäriin, näin toimi 78 % apteekeista tilanteessa, joissa asiakkaan lääkitys ei toiminut toivotulla tavalla. Suurimmalla osalla apteekeista ei ollut muun terveydenhuollon kanssa yhteisesti sovittuja toimintatapoja lääkehoito-ongelmien ratkaisemiseksi. Myös apteekin sisäiset toimintaohjeet olivat puutteellisia Johtopäätökset: Apteekkien ja muun terveydenhuollon välinen nopea viestintäkanava ja yhteisesti sovitut toimintatavat voisivat parantaa apteekkien mahdollisuuksia puuttua lääkehoito-ongelmiin. Apteekkien rooli lääkitysriskien hallinnassa tulee määritellä tarkemmin. Apteekkien ja muun terveydenhuollon välisessä yhteistyössä on paljon hyödyntämätöntä potentiaalia.

Poor adherence to and non-compliant use of medications are common in long-term patients, and it is estimated that only half of medication use worldwide is appropriate. Poor adherence to medication undermines public health, reduces the cost-benefit of resources invested in medication care, and burdens health care. Various interventions have sought to improve adherence to drug treatment, but they have not brought about the desired change in medication adherence. The aim of this master's thesis was to develop a method and pilot it to investigate the reasons for the non-compliant use of medications in the context of the medication reconciliation process. The aim of this new method was to find out the reason for non-compliant use of a medicine in a patient-centered way, and the possibility for the pharmacist to motivate the patient to use the medicine according to the instructions. In addition, it was examined whether the method can measure prevalence of non-compliant use of medicines differs according to the ATC classification of medicines and whether the total number of medicines contributes to the non-compliant use of medicines. The pilot study was carried out as part of a standard pharmacist's medication reconciliation process at Vantaa primary health care. The data required for the study were collected on the electronic HUSeCRF platform. Patients were collected to the extent that we were able to verify the functionality of the method and to plan the reporting of the results of the actual study with larger research data. The data were collected during the year of 2021. The theoretical framework of the study was the Medication-Related Burden model and the iceberg model of non-compliant use of medicines. The research material was analyzed using descriptive statistical analysis in IBM SPSS 27. The analysis of the data was done in terms of the functionality and development of the new method. A total of 8 patients participated in the pilot study (women 63% n = 5). Patients had an average of 16 medications per patient (range 8-22), and the last time their medications were reconciliated was on average 1 year ago. Non-compliant use of medicines was observed in 88% of patients (n = 7). In total, there were non-compliant use of medicines in the data for 21 drugs. The most common medicines which were used non-compliant were for the treatment of cardiovascular diseases. The total number of medicines and the number of non-compliant use correlated with each other (Pearson correlation coefficient 0.472), but the result was not statistically significant (p = 0.238). The most common reason for non-compliant use was a drug-induced side effect. After a motivational discussion which was involved in the medication reconciliation process with pharmacists, in 14 % of non-compliantly used medicines, patients decided to start taking the medication as directed. The pharmacist was able to motivate the patient to use the medicine as directed when the reason for non-compliant use of medicine was unclear instructions. In this study, a method was developed and validated to determine the reasons for non-compliant use of medicines. During medication reconciliation process, the pharmacist was able to find out the reasons for non-compliant use of medicines. Pharmacists may motivate the patient to use the drug as directed, however, most patients did not want to change the use of the medicine as directed. As the total number of medications increase, the probability of non-compliant use of medicines may increase.

The package leaflet (PL) is a technical document sheet included in medicine packages to provide guidance on safety and rational use of medicines for the user. The EU is increasingly encouraging the adoption of digital product information, which in time should be seen as the basic medicine information. The outdated package leaflet has for a long time been criticized by both patients and pharmaceutical operators. As a result, it is important to map the perspectives of various pharmaceutical operators on the electronic package leaflet. The aim of the study was to gain broader knowledge and deeper understanding of what opportunities and challenges the electronic package leaflet entails from the perspective of different pharmaceutical operators, and whether there are differences between opinions of the pharmaceutical operators. The study also sought to find out how the electronic package leaflet compared with the printed current leaflet from an environmental perspective. The study was conducted as a questionnaire e-survey, whose target groups were companies in the pharmaceutical industry, The Finnish Medical Agency (Fimea) and hospital pharmacies / departmental pharmacists. The material was collected over a three-week period in April 2022. The data was analysed both quantitatively and qualitatively. Based on the results of the study, it emerged that 55 experts, broadly across the pharmaceutical field, took part in the study. According to the pharmaceutical operators, the main opportunities of the electronic package leaflet were its ease of use and environmental friendliness. Patient safety, which is always a focal point when discussing medicines, would also increase as the users would have access to the most up-to-date medicine information (75 %, n = 41). In addition, the QR code on the medicine packages could be utilized when introducing ePL. The challenges, however, mainly concerned the user's lack of internet connectivity and incompetence in the use of e-services. Although pharmaceutical operators are of different opinion on the electronic package leaflet, it is highlighted that the majority of respondents (69 %, n = 38) believe that ePL would be an improvement and a more environmentally friendly alternative than the current printed leaflet. The study shown that there are differences in the perspectives on ePL between different pharmaceutical operators. The varying opinions on the electronic package leaflet depends on the respondent's position in the pharmaceutical sector. Despite the disagreement, the majority believe that ePL would be a positive development and a prerequisite for achieving the challenges of the future.