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

Finland has long traditions on the use and development of digital healthcare systems. This infrastructure, covering the entire population, has enabled the utilization of electronic healthcare records (EHR) collected in various registers for secondary purposes, such as research, development, and innovation (RDI) activities. Following the emergence of this activity, an operational environment supporting the reuse of data developed between these registers and data users, enabling diverse research activities. The Secondary Use Act, prepared on the basis of the General Data Protection Regulation (GDPR) and which came into force in May 2019, triggered many reforms for this operating environment. According to experts from various stakeholder groups, the reforms were seen as both beneficial and challenging, as observed in a small number of related studies already conducted. The purpose of this study was to investigate the current state of the impacts brought by the Secondary Use Act by mapping the views and opinions of representatives from different expert groups on key changes in the operating environment from their perspective and identifying potential areas for development. The study was conducted in early 2024 as a semi-structured interview study. The interviewees consisted of experts (n=8) from various stakeholder groups familiar with the operating environment for the secondary use of real-world data. The interviewees had extensive and significant experience with either the Secondary Use Act or its operating environment. Six distinct themes emerged from the material: data management in national registers, data utilization in research, the national process and guidance, the preparation process and culture of the Secondary Use Act, internationality, and actors and their equality. To identify new and significant observations, a comparison with previous research findings was conducted, ultimately identifying key factors that still challenge stakeholders. These factors related to inequalities among stakeholders, restrictions due to data protection requirements, lack of guidelines, and data harmonization. The results confirm the previous studies’ observations and highlight the particularly challenging areas for stakeholder groups in the current time. Overall, opinions about the data permit authority were mostly positive, while there was relatively more distrust towards register holders and legislators. Based on the study, there are clear grounds for developing the Secondary Use Act, but its timing is influenced by the progress of international projects, such as the EHDS model. Future research should increasingly focus on joint European projects to integrate Finland into the international operating environment.

There are significant inter-individual differences in the effects of drugs. These differences can be caused by, for example, other diseases, adherence to treatment, or drug-drug interactions. A drug-drug interaction can lead to an increase in the concentration of the active substance in the circulation (pharmacokinetic interactions) or a change in the effect of the drug without changes in plasma concentration (pharmacodynamic interactions). A drug-drug interaction can change the efficacy of a drug or affect the adverse drug reaction profile. The individual’s genetic background, such as diversity in drug-modifying enzymes (polymorphism), also has an effect on the efficacy and the risk for adverse drug reactions of some drugs. A pharmacogenetic test can be used to study how genetic factors affect drug treatments. The aim of this master's thesis was to examine the possibilities of personalized migraine pharmacotherapy from the perspective of pharmacogenomics and drug-drug interactions. Four online drug-drug interaction databases available in Finland were compared. Inxbase is the most widely used interaction database by physicians in Finland and it is also integrated into Finnish pharmacy systems. Other databases used in this study were the international professional database Micromedex as well as Medscape Drug Interaction Checker and Drugs.com Drug Interactions Checker. The latter two are open-access databases available for healthcare professionals and patients. Interaction searches were conducted in the selected databases between acute and prophylactic drugs used for the treatment of migraine (e.g. bisoprolol-sumatriptan). Fourteen acute and 12 prophylactic drugs were selected for this study based on the Current Care Guidelines in Finland (Käypä hoito), and the data were collected in Excel spreadsheets. The first search was completed in December 2019 and the second search in March 2020. In this study, many potential interactions were found between acute and prophylactic drugs used to treat migraine in Finland. For more than half of the drug pairs studied, a potential interaction was found in at least one of the databases. There were significant differences between the interaction databases regarding which interactions the database contains and how the severity of the interactions was classified. Of the interactions found, only 45% were found in all four databases, and each database contained interactions that were not found in the other databases. Even very serious interactions or drug pairs classified as contraindicated were not found to be consistently presented across all four databases. When selecting drug treatment for a migraine patient, potential drug-drug interactions between acute and prophylactic drugs as well as the patient's genetic background should be considered. Individualizing migraine treatment to achieve the best efficacy and to reduce the risk for adverse drug reactions is important because migraine as a disease causes a heavy burden on individuals, healthcare, and society. Pharmacogenetic tests particularly developed to help choosing migraine treatment are not yet available, but tests are available for few other indications in both public and private healthcare. The use of these tests in clinical practice will increase as physicians’ pharmacogenetic knowledge and scientific evidence on pharmacogenetic tests increase. Utilization of pharmacogenetic data requires that test results are stored in electronic health records so that they are available in the future, when changes are made to drug treatment of individuals. More studies are warranted to better understand the clinical impact of pharmacogenomics and drug-drug interactions in migraine care.

Background: Poor health literacy (HL) is associated to increased hospitalization and decreased seeking for screenings. Shared decision making can increase patient knowledge, decrease anxiety over the care process, improve health outcomes and reduce health care costs. Little is known about factors influencing health literacy and participation in treatment decision making in different population groups. Objectives: To investigate factors predicting HL and participation in the treatment decision making. Methods: A cross-sectional population online survey conducted in Finland in 2019 by Finnish Medicines Agency. Both health literacy and participation in the decision making were assessed by three statements that sum variables were created with score 1-5 (Cronbach’s alpha value 0.584 and 0.810). Age, gender, education, household income and most common chronic diseases were chosen as possible predicting factors. Two-variable Pearson’s chi-squared test was first used to find significant factors followed by logistic regression analysis to take into account several variables. Results: Of all the respondents (n=2104) 76.5% had good HL and 73.4% had willingness to participate in the treatment decision making. In the two-variable test older age (p<0.001), lower education (p<0.001), lower household income (p=0.001), higher number of chronic diseases (p=0.003), having cardiovascular diseases (p=0.003), diabetes (p=0.029) and cancer (p=0.001) predicted poorer health literacy. Male gender (p=0.001), not having chronic diseases (p=0.001), not having a musculoskeletal disorder (p=0.050) or mental health disorders (p<0.001) predicted poorer participation in the treatment decision making. In the logistic regression analysis older age and having cancer predicted poorer health literacy. Male gender and not having mental health disorders predicted less willingness to participate in the decision making. Conclusions: Older age and cancer predicts poorer health literacy and male gender poorer willingness to participate in the decision making. Further research should focus on investigating more in detail the contributing factors to these findings, and how health literacy in elderly and men’s involvement to the decision making could be improved.

Farmasian ammattilaiset ovat lääkealan asiantuntijoita, joilta vaaditaan uudenlaista osaamista muun muassa teknologiakehityksen myötä. Nykypäivän asiantuntijuus edellyttää alakohtaisen eli sisällöllisen osaamisen lisäksi geneerisiä eli yleisiä taitoja ja ammatti-identiteetin muodostumista. Geneerisillä taidoilla tarkoitetaan yleishyödyllisiä taitoja, kuten ongelmanratkaisu- ja kommunikointitaitoja. Ammatti-identiteetillä tarkoitetaan käsitystä omasta työminästä, jonka avulla omaa roolia ja työnkuvaa järkeistetään. Näiden elementtien muodostamaa osaamisen kokonaisuutta kutsutaan kompetenssiksi. Asiantuntijoilta vaadittavan osaamisen muutos on ohjannut yliopistoja vastaamaan paremmin työelämän tarpeisiin. Helsingin yliopistossa toteutettiin Iso Pyörä -koulutusuudistus, jossa koulutusohjelmia uudistettiin komeptenssilähtöisesti. Kaikkiin koulutusohjelmiin ja opintojaksoihin lisättiin osaamistavoitteet, jotka opiskelijoiden tulisi saavuttaa valmistumiseensa mennessä. Osaamistavoitteiden täyttymistä edistää esimerkiksi portfoliotyöskentely, minkä avulla opiskelijat pääsevät hyödyntämään ja kehittämään reflektiotaitojaan. Opiskelijat voivat tuoda opetuksen kehittämiseen aivan uudenlaista näkökulmaa avatessaan käsityksiään esimerkiksi hyvistä opetusmenetelmistä, mitkä ovat auttaneet heitä saavuttamaan laaditut osaamistavoitteet. Toisaalta opiskelijoiden näkökulmasta saadaan tietoa, mikä osaaminen voidaan kokea puutteelliseksi, jolloin opetuksen kehittäminen on mahdollista. Tutkimuksen tavoitteena oli selvittää opiskelijoiden käsityksiä omasta osaamisestaan ja ammatti-identiteetistään sekä millä tasoilla opiskelijat reflektoivat osaamistaan. Tutkimuksessa analysoitiin vuoden 2017 kolmannen vuosikurssin kandiportfolion loppureflektioesseet käyttäen aineistolähtöistä sisällönanalyysimenetelmää. Esseissä opiskelijat reflektoivat osaamistaan suhteessa farmaseutin tutkinnolle asetettuihin osaamistavoitteisiin ja pohtivat omaa ammatti-identiteettiään. Tulosten mukaan opiskelijat saavuttivat monipuolista osaamista lääkkeiden ja lääkehoitojen näkökulmasta sekä kehittivät geneerisiä taitojaan. Puutteellisesti hallittiin useimmiten kielitaito sekä yrityksen ja yhteiskunnan taloudelliset periaatteet. Opiskelijoiden mukaan farmaseutin ammatti-identiteettiä määrittelevät erityisesti lääkeosaaminen ja terveydenhuolto sekä ammatin arvostaminen. Opiskelijoiden pohtimat valmiudet mukailivat osaamistavoitteita. Opiskelijat osasivat arvioida omaa osaamistaan ja nostaa esille vahvuuksiaan ja heikkouksiaan. Opetussuunnitelmaan on onnistuttu sisällyttämään geneeristen taitojen opetus, sillä opiskelijat kokivat saavuttaneensa näitä taitoja pääasiassa hyvin. Opetusta tulisi kehittää kielitaidon ja liiketalouden kohdalla, sillä nämä koettiin usein puutteellisesti hallituksi. Ammatti-identiteettikäsitykset mukailivat kirjallisuutta, sillä muissa tutkimuksissa on saatu samankaltaisia tuloksia.

Syöpäsairaudet tai niiden hoito aiheuttavat potilaille usein huomattavaa fyysistä ja psyykkistä taakkaa. Merkittävien fysiologisten muutosten lisäksi hoidot johtavat usein voimakkaaseen ahdistuneisuuteen, psyykkisiin liitännäissairauksiin ja heikentyneeseen yleiseen elämänlaatuun. Näiden oireiden kasaantuessa ne heikentävät merkittävästi potilaiden elämänlaatua, arjen toimintakyvyn ja henkisen jaksamisen madaltuessa. Syöpäpotilaiden monet subjektiiviset oireet jäävät kuitenkin usein alihoidetuiksi tai hoitavalta taholta tunnistamattomiksi. Hoitoihin tai sairauteen liittyvien oireiden piiloon jääminen saattaa johtaa madaltuneeseen hoitoon sitoutumiseen, korkeampiin kuolleisuuslukuihin ja on terveydenhuollon tuottajan näkökulmasta tehotonta. Rutiininomainen ja spesifisti kohdennettu oireiden seuranta on tärkeää niiden oikea-aikaista ja tehokasta esilletuontia varten ja se on yhdistetty parantuneeseen hoitovasteeseen syöpäpotilailla. Kliinisten tulosten seurannan tueksi hoidon onnistumista voidaan seurata validoiduilla potilaslähtöisillä mittareilla (vointimittarit, PROM ja potilaskokemusmittarit PREM). Niillä voidaan saada oikein käytettynä riippumatonta ja reaaliaikaista tietoa potilaiden kokemasta terveydentilasta. Potilaskeskeisen (arvoperustaisen) terveydenhuollon kehitystyön edistyessä tutkimustieto hoidon vaikuttavuuden mittaamisesta potilaiden itse raportoimien tulosten avulla perinteisten kliinisten mittareiden lisäksi tulee korostumaan. Syöpähoitoja tarvitsevien määrän kasvu ja uusien, kalliiden pienmolekyylisten, biologisten, ja geeniterapiahoitojen markkinoille tuleminen, tuottavat taloudellisen paineen kestäville ja arkikäytössä vaikuttaville ratkaisumalleille hoidon toteutuksen tutkimukselle. Modernien viestintäjärjestelmien käyttö potilaiden raportoimien tulosten esilletuonnissa ja tallentamisessa voi tarjota mahdollisuuden parantaa vaikuttavuuden mittaamisen toteutusta kliinisessä arjessa. Tutkielman yhteistyöorganisaatio Istekki oy pyrkii kehittämään terveysteknologisia ratkaisuja julkisen terveydenhuollon käyttöön. Kartoittavan katsauksen periaatteiden mukaisesti, tutkimalla järjestelmällisesti olemassa olevaa kirjallisuutta selvitettiin, minkälaisia mittareita erilaisissa syöpähoitoja tarjoavissa ympäristöissä on käytetty. Katsauksen aineisto koostui 20 vertaisarvioidusta alkuperäistutkimuksesta, jotka keskittyivät potilaslähtöisten mittareiden käyttöön onkologisessa ympäristössä. Näistä saatiin tarkasteluun 28 erilaista validoitua potilaslähtöistä mittaria. Digitaalisten alustojen käyttö mittareiden käyttöympäristönä korostui kaikissa tutkimuksissa. Oikein käytettynä potilaslähtöiset mittarit edistivät potilaiden ja hoitohenkilökunnan välistä kommunikaatiota, potilastyytyväisyyttä ja mahdollistivat hoidon vaikutusten reaaliaikaisen seurannan potilasnäkökulmasta. Kuitenkin tekniset, kulttuuriset ja organisatoriset esteet, kuten koulutuksen puute, resurssien niukkuus ja tiedon puute (asenteet), ovat haasteita, jotka hidastavat mittareiden käyttöönottoa kliiniseen arkeen. Vointimittareiden tehokas hyödyntäminen edellyttää kattavaa koulutusta, selkeitä käyttöönotto- ja reagointistrategioita, sekä hyvin saatavissa olevaa teknistä tukea niin potilaille, kuin henkilökunnallekin.

In Finland, an increasing number of older adults who need around-the-clock assistance in their daily activities are taken care of in an intensive service housing unit, i.e., in a nursing home. The care organized in a nursing home also includes the resident's medical treatment and care. Medication safety and medication management processes have been widely studied in healthcare units, but there is a lack of similar research data from social care units. The topic is current because problems have arisen within the medication management process of the nursing homes, to which system-oriented solutions are needed. To develop risk management, additional information is needed on the risk points occurring in the medication management process of nursing homes. The study aimed to produce information on what kind of medication errors can be detected in the practical implementation of medication in a nursing home and in which stages of the medication management process they occur. The study was based on participatory observation data collected in a nursing home. The data was analyzed using quantitative and qualitative content analysis methods. The study’s theoretical framework was James Reason's human error theory and the Swiss cheese model. It was found that medication errors were common in the observed nursing home, as almost every fourth observed situation contained at least one medication error. Medication errors were detected at almost every stage of the medication management process. Storage errors (28 %) and medication administration errors (19 %) were detected more often than other types of errors. Detected storage errors were mostly related to not locking the medicine storage facilities or leaving medicines without monitoring. The most frequent administration error was medication omission. After storage and administration errors, the most commonly detected medication error types were error in cleaning or tidiness (7 %), ordering error (7 %) and error in medication administration checks (6 %). Other types of medication errors represented less than 5 % of the data. Almost a quarter of the errors were found to have happened to the resident, causing a medication safety incident. Actual adverse events could not be identified based on the data. About a fifth of the errors were near misses. Although about half of the errors did not happen directly to the residents, they were identified as medication, client, and patient safety risks. Pharmaceutical information was found to function as a good barrier in the medication management process, as some of the possible adverse events were prevented with the help of medical advice given to nurses. The medication management process of nursing homes could be developed by considering unit-specific risk factors and utilizing pharmaceutical expertise in the implementation of medical treatment. Through observation, it would also be possible to identify contributing factors of medication errors, enabling risk management activities to be targeted at the risk points of the medication management process. The study results offer valuable information about medication errors in nursing homes, which can be used in developing the medication management process.

Current treatments for major depressive disorder have notable limitations including the delay achieving the therapeutic effect. Ketamine has been shown to alleviate the symptoms of depression rapidly and promising findings have also been found when using nitrous oxide. However, the mechanisms behind rapid antidepressant effect are not fully discovered. It seems that rapid-acting treatments alter brain energy metabolism, enhance synaptic plasticity, and repair neuronal dysfunction connected to depression. Particularly, the activation of brain derived neurotrophic factor (BDNF) mediated tropomyosin receptor kinase B (TrkB) signaling has been connected to rapid antidepressant effect. Fasting is also known to induce BDNF production and it is thought to activate BDNF-TrkB signaling. In addition, both of these treatments alter the brain energy metabolism. The objective of this study was to find out how fasting and nitrous oxide alone and in combination affect the rapid antidepressant effect and synaptic plasticity related BDNF-TrkB signaling in mice. Another aim of the research was to determine whether the body temperature changes after these treatments as a marker of metabolic rate. The analyzed brain samples of the mice were collected 15 minutes after cessation of nitrous oxide administration. As a result, it was found that the fasting protocol used in this study did not activate the studied BDNF-TrkB signaling. However, after nitrous oxide administration, the studied signaling and markers related to synaptic plasticity were partly activated. The results from the combination of nitrous oxide and fasting were similar compared to nitrous oxide administration only. It is therefore conceivable, that the effects were caused exclusively by nitrous oxide. Furthermore, a fascinating finding related to energy metabolism was that nitrous oxide reduced the body temperature of the mice significantly 15 minutes after cessation of the gas administration. Overall, these results are promising and consistent with previous research indicating that nitrous oxide administration could be related to induced synaptic plasticity and therefore have antidepressant associated effects. Nitrous oxide could be used to understand the mechanisms behind rapid antidepressant effect and it could be a potential option to treat depression in the future. Based on these results, it seems that energy metabolism could be related to rapid antidepressant effect. It also supports the observations that all different rapid-acting treatments alter the brain energy metabolism.

Current therapies for depression have limitations in efficacy and delayed onset of action. Rapid-acting antidepressants like ketamine, an N-methyl-D-aspartate receptor (NMDA-R) antagonist, have gathered attention as an improved treatment option. However, the neurobiological mechanism underlying their antidepressant effect remains uncertain. Integral mechanisms of action seem to be alterations in synaptic plasticity, global cortical excitation, and repair of neuronal dysfunctions prevalent in the pathophysiology of depression. Emerging evidence does suggest that antidepressant drugs act by facilitating brain derived neurotrophic factor (BDNF) mediated tropomyosin receptor kinase B (TrkB) signaling. Interestingly, rapid-acting antidepressants seem to increase TrkB-associated signaling after their acute pharmacological effect has dissipated, and when animals become sedated and show various physiological changes associated with deep sleep (e.g., slow wave EEG activity, SWA). Indeed, recently a close relationship between sedation and molecular signaling implicated in antidepressant effects has been discovered. The aim of this study was to explore the relationship between sedation and molecular signaling associated with antidepressant effect. This was carried out by assessing the localization of TrkB-associated phosphorylation signaling in the adult male mice medial prefrontal cortex (mPFC) using dexmedetomidine, a sedative. Key signaling molecules such as ribosomal protein S6 kinase (p70S6K), ribosomal protein S6 (rpS6), glycogen synthase kinase 3 (GSK3), mitogen activated protein kinases (MAPKs) and immediate early gene c-Fos, were examined through immunohistochemical (IHC) analysis. Two separate experiments were conducted using naïve adult 8-13-week-old (n=8 and n=10) male C57BL/6JRccHs mice. In the experiments mice were injected intraperitoneally with either dexmedetomidine (0,05 mg/kg, Dexdomitor®), or saline followed by a 30-minute recovery period whereafter mice were euthanized. In the first experiment, medial prefrontal cortex samples were collected immediately post decapitation for western blot (WB) analysis. The results showed that dexmedetomidine significantly activated TrkB-associated signaling in brain homogenates, consistent with expectations. In the second experiment, mice were perfused with 4% paraformaldehyde (PFA) before brain collection for IHC analysis. However in this experimental setting, no significant difference in the localization of TrkB-associated signaling induced by dexmedetomidine was observed compared to saline. Although, no significant results for signal localization were observed, the results provide insights into the neurobiological effect of sedation induced TrkB-signaling. Further research factoring in limitations is needed to uncover the involvement of physiological states in antidepressant mechanisms.

Indomethacin is a poorly soluble but highly permeable drug, and its biological availability can be improved by enhancing its solubility. In this study, co-crystals and co-amorphous systems of indomethacin and nicotinamide were prepared in a 1:1 molar ratio, which have previously been shown to enhance the solubility of indomethacin. It has also been observed that the co-amorphous indomethacin-nicotinamide system crystallizes into a co-crystal during storage. This study aimed to further investigate the properties, solubility, and stability of these compounds, and tablet formulations were also prepared from the co-crystal and co-amorphous systems. Powdered co-crystals and co-amorphous systems, as well as tablets prepared from them, were stored at 25°C with 60% relative humidity and at 40°C with 75% relative humidity, and their solubilities were studied for 12 weeks. The stability of the samples was also examined using Fourier infrared spectroscopy and differential scanning calorimetry over the same period, and changes in the physical properties of the tablets were monitored throughout the study period. Additionally, the effect of HPMC on the prevention of indomethacin recrystallization was investigated. Both the co-amorphous and co-crystalline forms were found to enhance the solubility of indomethacin in both powder and tablet formulations in this study. The co-crystal was stable, with no changes observed in its crystal structure or solubility over the 12-week study period. However, handling the co-amorphous material turned out to be difficult due to its low glass transition temperature of 19.68°C, causing the powder to soften at room temperature. During storage, it was shown to crystallize into a co-crystal, but its solubility properties were weaker to those of the actual co-crystal. None of the solubility tests showed evidence of indomethacin recrystallization, so the potential effect of HPMC on this phenomenon could not be determined in the study. Warmer and more humid conditions were found to increase the tensile strength of the tablets, resulting in slower dissolution.

The ABCG2-protein is an ATP-dependent half transporter. It is found on apical membranes in intestine, liver, kidney, blood-brain barrier and placenta where it regulates absorption, distribution and elimination of many drugs, but also natural compounds and endogenous metabolites. Natural variation found on the ABCG2-gene can alter protein expression and transport activity. The altered function has been linked to pharmacokinetic changes and developing of diseases like gout. Studying natural ABCG2-variants and their effect gathers knowledge not only on their effect on pharmacokinetics but also on the ABCG2- transporters’ mechanism of function. The aim of this study was to combine an activating (I456V or H457R) and an inactivating (Q141K, F431L or T542A) non-synonymous single nucleotide variant in the same gene to study their combined effect on the ABCG2-transporter expression and active transport. Mutations were incorporated into the ABCG2- gene by site directed mutagenesis and the protein was expressed on HEK293-cells. The transport activity for Lucifer-Yellow and estrone sulfate was measured using HEK293-ABCG2-vesicles produced from cell membranes. The protein expression was measured with Western blot and mass spectrometry proteomics. Based on this study, different mutations together can alter each other’s effects, but the combined result is not always equal to the sum of variations. T542A-mutation did not show significant increase on the protein expression on any of the T542A-combinations, even though it has had such an effect in earlier studies. I456V, earlier expressed like wild type ABCG2, seemed to increase protein expression in all combinations. Q141K, F431L and T542A -mutations had lowering not expression dependent effect on the transport activity. F431L-mutation being so dominant that either of the two activating mutations could not restore the active transport in combinations. As seen before, H457R-variant seemed to cause a significant substrate specific activating effect on transport activity also in this study when combined with other mutations. However, H457R had a strong lowering effect on the protein expression and two of the combinations did not produce enough protein for active transport. As seen in this study, the ABCG2-doublemutations can cause altered ABCG2-function and lead to pharmacokinetic changes. These types of in vitro studies are important in studying these less common genetic variants which in lack of study subjects can be hard to study on clinical trials.