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(2024)Lääkehoitoa toteutetaan erilaisissa toimintaympäristöissä sekä sosiaali- ja terveydenhuollossa, että sen ulkopuolella. Lääkehoitoa toteuttavat pääsääntöisesti sosiaali- ja terveydenhuollon ammattihenkilöt, mutta ympäristön mukaan vaihdellen myös lääkehoidon koulutusta vähän tai ei lainkaan saaneet. Lääkehoidon osaamisen varmistaminen on aina työnantajan vastuulla. Keski-Uudenmaan hyvinvointialueella on ruuhkautuneiden näyttöjen myötä tunnistettu tarvetta keskitetyille näytöille. Tehty pilottitutkimus tuo arvokasta tutkimustietoa näyttötyöpajasta osana lääkehoidon käytännön osaamisen varmistamisen prosessia, sillä aikaisempia tutkimuksia aiheesta ei ole. Tutkimuksen keskeisenä tavoitteena oli tutkia näyttötyöpajan toimivuutta lääkehoidon käytännön osaamisen varmistamisessa, sekä mitä resursseja näyttötyöpajan järjestäminen organisaatiolta vaatii ja mikä olisi optimaalinen näyttötyöpajan osallistujamäärä. Pilottitutkimus toteutettiin järjestämällä näyttötyöpaja, jossa Keusoten yksiköissä työskentelevät nimikesuojatut terveydenhuollon ammattihenkilöt (n=15) osoittivat lääkehoidon käytännön osaamistaan. Näyttötyöpajassa lääkkeiden jakamisen näyttöjä ottivat vastaan farmaseutit (n=3) ja lääkkeiden antamisen näyttöjä sairaanhoitajat (n=2). Aineistona tutkimuksessa toimi näyttötyöpajassa näyttöjä antavien ja vastaanottavien antama palaute, joka kerättiin puolistrukturoidulla palautelomakkeella paikan päällä. Palautekysely lähetettiin myös näyttöjä antaneiden esihenkilöille ja vastaaville sairaanhoitajille sähköisellä Microsoft Forms- lomakkeella. Aineistoa analysoitiin tilastollisesti kuvaavalla tavalla sekä induktiivisella sisällönanalyysillä hyödyntäen Microsoft Excel -ohjelmaa. Näyttötyöpajaan osallistuneet kokivat näyttötyöpajan kehittävän lääkehoidon osaamista. Näyttötyöpajan koettiin nopeuttavan ja helpottavan osaamisen varmistamista sekä. Esihenkilöt ja vastaavat sairaanhoitajat kuvailivat näyttötyöpajan myös vapauttavan näyttöjen järjestämiseen kuluvia resursseja muuhun hoitotyöhön. Sekä osallistujat että näytön vastaanottajat kokivat näyttötyöpajan vertautuvan huonosti aitoon työtilanteeseen. Keskeisiksi näyttötyöpajan kehityskohteiksi nousivat parempi organisointi, tiedonkulun vahvistaminen ja näyttöjen tasalaatuistaminen. Mukauttamalla näyttötyöpajaa enemmän aidon työtilanteen kaltaiseksi voisi näyttötyöpaja tukea osaamisen kehittymistä paremmin, sekä parantaa työyksikön lääkitysturvallisuutta. Näyttötyöpajaa tulisi tutkia ja kehittää lisää, jotta siitä saataisiin sujuva osa osaamisen varmistamisen prosessia. Näyttötyöpaja koettiin pääosin hyödylliseksi ja se koettiin tarpeelliseksi interventioksi helpottamaan ruuhkautunutta lääkehoidon osaamisen varmistamista.
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(2024)Cardiac fibrosis (CF) is a physiological response to various stress factors encountered by the heart, with the aim of maintaining proper functioning of this vital pump in an altered situation such as increased mechanical stress or sudden injury in heart muscle. CF is characterized by excessive production of extracellular matrix (ECM) components and stress fibers in cardiac tissue, accompanied by morphological changes of the heart muscle. The responsible cells behind these changes are fibroblasts (FBs) that undergo phenotypic change by transdifferentiating into myofibroblasts (myoFBs). Although being initially a supportive response, CF can lead to deterioration of the heart performance and even heart failure, if prolonged. Given the lack of effective enough therapies against CF, and the strong involvement of CF in cardiovascular diseases (CVDs) that are associated with high mortality rate, the need for new effective therapies is urgent. Indeed, a diversity of approaches to fight CF have been proposed, among them protein kinase C (PKC) and its signaling cascades. PKC has been shown to play a role in fibrosis and many studies suggest antifibrotic properties of PKC, yet the results are challenged by the opposite findings. Despite the dichotomous results, new small molecules that function as partial agonist of PKC seemed to be a promising strategy for the treatment of fibrosis. To further explore the role of PKC activation in CF, the aim of this study was to first develop and characterize a human cardiac fibroblast (HCF)-based CF model, in which the effects of seven new PKC modulators on HCFs could then be evaluated. To create the CF model and provoke a fibrotic response, HCFs were treated with either transforming growth factor β1 (TGF-β1), Angiotensin II (Ang-II), endothelin-1 (ET-1), or combination of treatments, followed by determination of HCF proliferation activity and α-smooth muscle actin expression (α-SMA), a marker of myoFBs. After the treatments, the original goal was to continue in compound testing phase by exposing the HCFs to the PKC-modulators to see whether any differences could be determined in α-SMA expression or proliferation activity. However, no considerable effects of fibrosis-inducing treatments on the activation of HCFs were observed, thus preventing this progression. Nevertheless, toxicity tests were performed on the compounds and the results indicated relatively low overall toxicity for the lower concentration: six out of seven compounds yielded over 70% HCF viability at 3 μM concentration with three of them reaching even over 80% viability, while the corresponding value for the previously published PKC agonist HMI-1a3 was 54%. Although these results are promising for the lower concentrations of PKC-modulators, it is obvious that more in-depth studies are required prior to drawing any unambiguous conclusions.
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(2024)Ischemic heart disease, which often progresses to heart failure, is one of the leading causes of death worldwide. Ischemic conditions result in the death of heart muscle cells i.e. cardiomyocytes. Due to their poor regenerative ability, lost cardiomyocytes are replaced with a fibrotic scar. The loss of cardiomyocytes further leads to compensatory mechanisms, including cardiomyocyte hypertrophy and fibrosis. When prolonged, these responses turn maladaptive leading to pathological cardiac remodeling and alterations in cardiac function. In order to achieve better clinical results, discovery of new drug treatments that promote cardiomyocyte regeneration and decrease pathological cardiac remodeling would be invaluable. One potential target is serine/threonine protein kinase AKT (also known as protein kinase B), a key component of the PI3K/AKT signal pathway, which has been shown to be one of the mechanisms regulating heart regeneration and remodeling post-ischemia through its several downstream targets. The aim of this study was to investigate the effects of AKT-targeted compounds with and without endothelin-1-induced hypertrophy on the phenotype of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The compounds were either commercially available substances linked to AKT regulation, or new experimental compounds synthesized at the Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki. Prior to the hiPSC-CM phenotypic studies, the toxicity of the compounds was investigated using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in three different cardiac cell models: human cardiac fibroblasts (HCFs), H9c2 cells derived from embryonic rat myocardium, and hiPSC-CMs. Compound-induced proliferative and hypertrophic responses of hiPSC-CMs were studied using immunofluorescence staining and high-content analysis. Toxicity screening of the compounds showed that only AKT045 was concentration-dependently toxic in all three cell types after 24-hour treatment. Based on the toxicity screening, several compounds caused more pronounced concentration-dependent effects in H9c2 cells as compared to hiPSC-CMs and HCFs. The most considerable effects were observed with AKT042 and AKT048, as they decreased the viability of H9c2 myoblasts 46% and 55% at 30 μM concentration, respectively. In phenotypic studies, AKT050 decreased hiPSC-CM proliferation significantly. This result indicated inhibition of AKT and was consistent with previous studies. Commercially available AKT activator SC79 did not induce expected effects, as it tended to attenuate both proliferative and hypertrophic response in hiPSC-CMs. However, AKT activation has been shown to increase both proliferation and hypertrophy in previous studies. Other compounds induced a prohypertrophic rather than an antihypertrophic effect in hiPSC-CMs. Although proliferative responses to other compounds varied slightly, AKT042 and AKT043 seemed to increase the proliferation of hiPSC- CMs. However, the AKT activation or inhibition could not be confirmed in this study and therefore additional studies are needed to assess the full extent of effects and mechanisms of these compounds.
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(2024)Alzheimer's disease is a progressive neurodegenerative disease of the central nervous system, in which accumulation of amyloid β plaques and hyperphosphorylated tau proteins cause neuronal death, loss of synapses, and impaired neurotransmission. Alzheimer's disease's main symptoms are memory dysfunction (dementia) and decline in cognition. One of the most significant factors believed to cause dementia in Alzheimer's disease is the destruction of dendritic spines. Dendritic spines are small protrusions of dendrites where most of the glutamatergic synapses are located and where mainly excitatory synaptic functions occur. Loss of dendritic spines is directly correlated to the loss of synaptic function, which then causes memory dysfunction and impaired cognition. Also, the morphology of dendritic spines is important for their stability and strength. The spine head's size is correlated to the number of postsynaptic receptors. Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are unconventional neurotrophic factors, which have neuroprotective and -restorative effects via regulating endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Accumulation of unfolded and/or misfolded proteins in the lumen of ER causes ER stress, which then activates UPR, which again maintains protein homeostasis by reducing the amount of unfolded/misfolded proteins. In this study, we injected CDNF, MANF or PBS into the hippocampus of C57BL/6 mice to analyze whether they increase dendritic spine density and improve their morphology, especially by increasing the density of mature spines. This study shows that MANF increases dendritic spine density and CDNF does not. MANF increases the density of most of the mature and immature spines but interestingly decreases the density of mature stubby spines. These results are very promising and MANF's effect on dendritic spine formation should be studied further. In another separate study, we investigated whether CDNF and MANF activate the ERK1/2 pathway on organotypic hippocampal slices. This pathway is important for memory formation, and another neurotrophic factor, brain-derived neurotrophic factor (BDNF), has been shown to increase dendritic spine density by stimulating the ERK1/2 pathway. CDNF and MANF activate UPR, but there is some evidence that UPR might also activate ERK1/2, which could then explain CDNF's and MANF's mechanism of action. CDNF and MANF-treated hippocampal slices had visually thicker and darker bands in ERK1/2 antibody staining but any conclusion cannot be made because of the sample sizes being too small.
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(2024)Medication safety is critical in health and social care, and community pharmacies significantly participate in managing medication safety risks. The information systems in community pharmacies are pivotal, yet understudied tools supporting this task. This study investigates community pharmacy information system-related medication safety incidents reported by Finnish community pharmacies, focusing on how information systems act as defences or contributing factors to such incidents. The study is based on 1222 information system-related medication safety incident reports from the HaiPro system between October 2022 and September 2023. The structured fields of the incident reports were analysed with descriptive quantitative analysis using Microsoft Excel. An abductive content analysis was performed on narrative texts of the incident reports to identify information system-related risks or defences in the incidents. Reason's human error theory acted as a theoretical framework in this study. Results indicated that in 96% (n=1168) of the incidents, information systems were contributing factors, primarily during the selection of medicinal products for dispensing (n=945). The most common issue was the community pharmacy information system not offering generic substitutes for market-exited medicinal products (n=282). Another notable issue was compatibility problems between community pharmacy information systems and Electronic Patient Record (EPR) systems or between different community pharmacy information systems (n=154). Conversely, barcode recognition emerged as the most reported defence, preventing errors in 96% (n=52) of defensive cases (n=54). The study underscores the dual role of community pharmacy information systems in medication safety both as defences and contributing factors. It highlights the need for continuous system development and possible regulatory changes to enhance their effectiveness as defences. Future research should explore these systems' roles using alternative methodologies to address underreporting and better quantify their impact on medication safety.
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(2024)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.
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(2024)Falls are common in older people, some of which result in serious injuries. Falls are a burden on the health care system and preventing them could reduce the burden. Risk factors for falls include impaired vision, certain chronic diseases, female gender, old age, alcohol consumption, foot problems and environmental factors. Certain medications also increase the risk of falls. Drugs affecting the central nervous system and drugs affecting the cardiovascular system are the main drugs that increase the risk of falls, known as fall-risk-increasing drugs (FRIDs). The aim of the thesis was to analyze the medication lists of patients who had fallen or were at risk of falling and who were living at home and were transported by the emergency services to the HUS emergency unit in Jorvi. The aim of the study was to investigate whether the medication lists of patients (n=216) included fall-risk-increasing drugs, potentially inappropriate medication, adverse risks associated with the risk of falling and drug-drug interactions. The study also compared three groups of patients with different fall statuses. Group 1 consisted of patients who had fallen and patients at risk of falling (n=79). Group 2 consisted of patients at risk of falling who had not fallen (n=85). Group 3 included patients who had fallen but were not at risk of falling (n=52). Microsoft Excel and IBM SPSS Statistics were used to analyze the data. In the data 52.3% of patients were on polypharmacy. Patients in group 3 had fewer regular medications than patients in group 1 (p=0.001) and group 2 (p=0.010). Almost half (46.3%) of the patients in the data set had at least one FRID medication in regular use. Group 1 patients had the highest number of FRIDs in use and Group 3 patients the lowest. The most frequently used FRID was furosemide (n=54). According to the Med75+ database, about a quarter of patients (27.3%) and almost half (48.6%) of patients according to the Beers criteria were regularly using potentially inappropriate medication (PIM) in older people. Level D adverse events associated with risk of falls were present in 28.2% (n=62) of patients in the whole dataset when considering regular medication use. Multiple patients were taking risperidone, amitriptyline and tramadol, which belong to FRIDs and PIMs medicine and are associated with D-level adverse risks. In the whole dataset, only a few patients (n=12) were found to have a category D interaction with regular medications. Class C interactions were found in 38.9% of patients. The falls risk assessment performed by emergency medical services was reasonably good at predicting medical risk factors associated with falls. Particular attention should be paid to patients at risk of falling who have not fallen yet. The reduction of medication factors that increase the risk of falls could potentially prevent falls in the future. Once patients at risk of falls have been identified, pharmacists could be used in the emergency department to identify and possibly unwind medication factors that increase the risk of falls in the older people, in collaboration with physicians. The knowledge of pharmacists could also be utilized to review medication risks associated with falls in community pharmacies.
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(2024)Medicines are essential to human and animal well-being. They do, however, cause harmful effects to the environment, humans, and animals – especially to aquatic organisms. The most significant route for pharmaceutical residues to end up in the environment is the conventional use of medicines in people. Due to ageing of the population and medicalization, the amount of medicines used to treat humans will only increase in the future. Pharmaceutical residues may also end up in the environment from production sites of pharmaceutical manufacturers, which causes harmful environmental effects locally. Also, the transport of raw materials and finished pharmaceutical preparations produces climate emissions. There is still work to be done to improve sustainability of the pharmaceutical sector. Incorporating environmental criteria in public procurement of medicines is seen as a method of advancing responsibility within the sector. In the spring of 2023, the HUS Pharmacy tender invitations included, for the first time, environmental criteria. Yet at this point, the criteria did not have a decisive role in decision-making. The aims of this study included discovering how the representatives of those pharmaceutical companies participating in the HUS tender invitations experienced the HUS environmental criteria, how they viewed the environmental criteria in public procurement of medicines in general, and which actions or incentives they considered the most effective tools in guiding pharmaceutical production towards a more sustainable direction. The study was conducted as an internet survey and video interviews. The environmental criteria of HUS were perceived as quite clear but there had been difficulties in seeking for the information needed. This was due to the limited time available and the internationality of the organizations, among other things. The respondents hoped for the adoption of uniform criteria, which would easen responding to different tender invitations and reduce the time needed for fact-finding. This kind of criteria was hoped to be prepared for in collaboration with different stakeholders, also considering internationality. Keeping environmental criteria involved in tender invitations was seen as one possible means of advancing sustainability of pharmaceutical manufacturing. Clear and agreeing views were not achieved for all questions presented, but instead the responses divided quite a lot for some questions. This is probably partly connected to the complexicity of the subject and the fact that some of the questions presented were seen as somewhat ambiguous. Altogether, it may be stated that the general atmosphere was more positive than negative towards the environmental effects being taken into account. Utilizing environmental criteria in promoting environmental responsibility of the pharmaceutical sector will be of use. But when formulating the criteria, it should be remembered that too strict criteria may result in a decline in the amount of offers to tender invitations.
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(2024)Parkinson’s disease (PD) is a prevalent neurodegenerative disease characterized by movement disorders, such as bradykinesia, akinesia, and tremor. The degeneration of dopaminergic neurons in the central nervous system (CNS) is the most central aspect of the pathophysiology of PD-related movement disorders. The treatment of PD motor symptoms is based on increasing the diminished dopaminergic signalling in the CNS. This can be achieved by using medications such as dopamine agonists and monoamine oxidase B inhibitors. Levodopa, which acts as a precursor of dopamine in the body, is currently considered the most effective treatment for PD motor symptoms. Unlike dopamine, levodopa can cross the blood-brain barrier. Thus, levodopa must reach the CNS before being metabolized into dopamine to achieve the desired therapeutic effect. Dopa decarboxylase (DDC) inhibitors and catechol-O-methyltransferase inhibitors have been co-administered alongside levodopa to reduce its peripheral metabolism. However, when administered orally, levodopa is also metabolized in the gut by tyrosine decarboxylase, an enzyme produced by gut bacteria. Inhibi tion of bacterial tyrosine decarboxylase (TyrDC) could increase the effectiveness of levodopa treatment and reduce the needed levodopa dosage. The aim of this study was to synthesize and assess the biological activity of novel analogues of previously identified hit compounds which are dual inhibitors of TyrDC and DDC. Our goal was also to gain a deeper understanding of the structure-activity relationships of these compounds. Some of the compounds synthesized in this study were able to inhibit both TyrDC and DDC. Unfortunately, they were also either toxic towar ds human cells, and/or lacked efficacy in a bacterial cell-based assay used to determine the inhibition of levodopa metabolism. However, the data generated in this study can be utilized to design and synthesize new analogs to discover more efficacious and safer TyrDC and DDC dual inhibitors.
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(2024)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.
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Biologisiin lääkkeisiin ja biosimilaareihin liittyvä osaaminen suomalaisissa avohuollon apteekeissa (2024)Biological medicines are used, for example, in the treatment of diabetes, cancer, and autoimmune diseases. Biological medicines cause a significant part of the costs of prescription drugs in outpatient care. In Finland, automatic substitution of biological medicines will be introduced in 2024–2025 to promote the use of biosimilars and to increase price competition. When substituting biological medicines, pharmacists are required to counsel the customer and ensure proper use of the new administration device. The objective of this study was to study Finnish community pharmacists’ knowledge about biological medicines and biosimilars and the need for further training. Data was collected with an electronic questionnaire and analyzed using frequencies and percentages. Associations between background variables and readiness for automatic substitution were analyzed using crosstabulation and chi-squared test. Differences in drug-specific knowledge were compared using sum variables. Most pharmacists (n=899) answered that they understood at least the basics of what biological medicines and biosimilars are. The important role of biosimilars in reducing society's drug costs seemed to be well understood, but only one in four (25.0%) felt that they were ready for automatic substitution. Master’s degree in pharmacy, graduating as a pharmacist (BSc) between 2010 and 2022, and working in community pharmacy for less than 10 years after graduating as pharmacist (BSc) increased the experience of readiness for automatic substitution. Previous work in the pharmaceutical industry or wholesale trade, in official positions or in research and teaching positions also increased the experience of readiness for automatic substitution, as well as clinical expertise or additional training in the field of pharmacy. Drug-specific knowledge seemed to be best about enoxaparin and insulins. Further training was needed especially on the differences of administration devices and giving injection advice. The strength of this study was a representative sample of pharmaceutical personnel working in Finnish community pharmacies, although low response rate weakens generalizability of the results. The results give an indication of how Finnish community pharmacists assessed their knowledge about biological medicines and biosimilars before the introduction of automatic substitution in Finland. Further research is needed to monitor the development of knowledge about biological medicines and to examine customers’ experience on the quality of medication counselling related to biological medicines at pharmacies.
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(2024)Barcode-assisted medication administration can be used to prevent medication errors in pediatric hospital settings, as the medicine and the patient can be safely identified during the drug preparation and administration. The use of barcode-assisted medication administration has been examined in a few qualitative studies. In addition to the benefits, many challenges related to the implementation of this new workflow have been identified. The aim of this study was to identify facilitators and barriers related to the use of barcode-assisted medication administration in a children's hospital. The topic has not been studied in Finland before. A qualitative focus group study was carried out at HUS Helsinki University Hospital in the Department of Children and Adolescents. Ward pharmacists (n=14) were selected for the focus groups (n=3) by purposive sampling to identify persons using barcode-assisted medication administration on their daily work. Two researchers conducted the inductive content analysis independently, after which a consensus was formed first with these researchers and later with the entire research group. COREQ checklist was used to support detailed reporting and to consider the factors that might affect to the reliability of the study in each phase of the study. Four main themes were identified from the data; the barriers, the risk behavior caused by the barriers, the facilitators and the development ideas. The barriers included challenges related to negative attitudes of the end-users, barcodes on drug packages and labels, use of the electronic health record system, workstations and equipment, as well as orientation, competence and management. The barriers caused risk behavior that was related either to the system or to the end-user. On the other hand, the facilitators were associated with the positive experience of the end-user, the increase in expertise and multi-professional cooperation, the functions of the electronic health record system that supported the preparation and administration of the medicines, as well as the benefits of the barcode-assisted medication administration workflow. The development ideas aimed to remove the barriers and the risk behavior related to the use of barcode-assisted medication administration. The users found that the use of barcode-assisted medication administration increased patient and medication safety, although there were still many challenges associated with the new workflow. Barcode-assisted medication administration can be used to reduce medication errors and protect patients from adverse events. The results of this study can be used to develop the usability of barcode technology and their implementation.
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(2024)Finland is one of the first countries in the world to introduce automatic substitution of biological medicines in community pharmacies. The automatic substitution for biological medicines will be introduced in stages in years 2024–2026. The successful and safe transition requires guidelines for implementing new operating practices and dispensing practices, including possible continuing education to community pharmacists to ensure their sufficient competence e.g. in advising patient how to use their administration devices. Therefore, the change process requires competence development and management. The purpose of competence management is to create, maintain and develop an organization. Competence management is part of strategic personnel management, which ensures that the organization has the core competence and other necessary competence to implement its mission. The aim of this master's thesis was to study the competence management while preparing for the automatic substitution of biologics in community pharmacies in Finland. The research focused on the competence management practices and competence development needs within the framework of 1) personnel management and competence development and 2) automatic substitution of biologics. The research was carried out as a qualitative focus group discussions (FGDs) (n = 6, altogether of 23 participants) in January 2023. Voluntary participant participated in the group discussions from community pharmacies of different sizes and from different parts of Finland. Of the participants there were pharmacy owners with M.Sc. (Pharm) degree (n = 5/23, 22 %), pharmacists with M.Sc. (Pharm) degree (n = 10/23, 43 %) and pharmacists with B.Sc. (Pharm) degree (n = 8/23, 35 %). Qualitative content analysis was carried out inductively, i.e. data oriented. In addition to the themes emerging from the research material, the main themes of the discussion body partially guided the analysis. SRQR checklist was used to support detailed reporting to evaluate the reliability of the study. The data analysis identified 1) factors related to the current practices and needs of competence management and needs for competence development, 2) methods applicable for competence development of pharmaceutical personnel, and 3) functions related to the delivery of the biological medicine, such as medication counselling, support for the patient's self-care and a possible substitution of biologics, as well as the functions and tools that support these. The results of this study indicated that competence management practices vary between community pharmacies, and the competence management actions were not always systematically planned. Community pharmacies did not yet have operating models or practices for implementing automatic substitution of biologics, although they perceived that automatic substitution practices for inhalable medicinal products could perform as a model for the substitution of biologics. Despite some perceived uncertainties concerning implementation of automatic substitution of biologics, community pharmacists and pharmacy owners had mainly positive attitude towards the coming changes.
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(2024)Light-sensitive liposomes have gained attention for their ability to deliver cargo to tissues, offering spatiotemporal control over drug release. Red-light wavelengths have been utilized as an external trigger in light-sensitive reactive oxygen species (ROS)-mediated drug delivery, due to their favorable properties, such as the low light absorption by tissue chromophores. The ROS-sensitive drug delivery systems use photosensitizers (PS), which upon light exposure generate ROS in the presence of molecular oxygen. Palladium(II)phthalocyanine (Pd(II)PC), a new second-generation photosensitizer, can upon light irradiation generate relatively high singlet oxygen concentrations, enabling the efficient oxidation of the unsaturated lipids. The oxidation of the lipids leads to the disruption of the liposome bilayer and eventually, the release of the encapsulated cargo. To gain deeper insight on the phthalocyanine-labeled liposomes in drug delivery, a red light-triggered cationic liposome formulation encapsulating Pd(II)PC was formulated. The characteristics of the liposomes, the release mechanisms, and the release quantities of calcein (623 Da) and fluorescent-conjugated dextrans (4 000-70 000 Da) were studied following red-light exposer with 630 nm, 450 mW/cm2 laser while utilizing varying Pd(II)PC-loading quantities. Following oxygen removal and temperature-induced release studies, the mechanism of release of the liposomes was principally observed to be light-triggered reactive oxygen species-mediated. In the light-induced release studies an effective release of the calcein, and a relatively effective release of the Rhodamine B dextrans (10 kDa, 70 kDa) were observed from the liposomes via the Pd(II)PC-generated and reactive oxygen species-mediated oxidation of the unsaturated lipids. The release of the biomacromolecules from the liposomes was observed to require longer irradiation times than that of calcein. The longer irradiation times likely lead to deeper oxidation of the unsaturated phospholipids, resulting in a comprehensive eruption of the liposome bilayer. The comprehensive eruption of the liposome bilayer eventually enables the sufficient release of biomacromolecules from the liposomes.
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(2024)To develop a closed-loop medication management process, monitoring the effects of medication should be integrated into patient information systems through structured recording methods. Sufficient documentation of medication monitoring is a prerequisite for implementing effective medication management and ensuring good quality, individualized care for patients. Medication management for patients with intellectual disabilities on the autism spectrum can be extremely challenging. The characteristics of intellectual disabilities and autism spectrum disorders, comorbidities, and polypharmacy make medication management and monitoring challenging. This study focused on patients with difficult behavioural symptoms. The study aimed to identify the most important symptoms to monitor in assessing the effects of medication in patients with intellectual disabilities on the autism spectrum. Additionally, it defined the time points from the initiation of medication when the effects should be assessed. The study was conducted as a two-round study using the Delphi consensus method in January-February 2024. The expert panel consisted of 12 experts in intellectual disabilities, autism spectrum disorders or in the field of medicine. Lists of behavioural symptoms, other symptoms, and monitoring time points were compiled for the study based on literature and the expertise of the research group. Experts were presented with a list of symptoms, and in the first round, symptoms that exceeded a consensus threshold of 50% proceeded to the second round. In the second round, experts ranked symptoms based on their importance for monitoring using Likert-scale questions. The data were analysed using quantitative and qualitative methods. Experts considered 9 behavioural symptoms and 22 other symptoms as highly important or important to monitor. The experts identified severe symptoms indicating self-harm or harm to others as the most critical behavioural symptoms to monitor. The most important other monitored symptoms included common comorbidities and symptoms within the patient group or adverse effects of medication. The effects of medication should be evaluated regularly, at least at the 4-week mark after initiating medication and after 3 months evaluations should be conducted at intervals of every 6 months. Monitoring the effects of medication was perceived to pose many challenges, and monitoring is not always carried out at a sufficient level. Many different symptoms should be monitored because patients are individual and present a variety of symptoms. It is essential to have a good understanding of the patient's condition before starting medication to assess the medication's impact on the patient's behaviour or other symptoms. The study highlighted the lack of structured monitoring forms and the need for monitoring tools.
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(2024)The potential of extracellular vesicles (EVs) as diagnostic markers and drug delivery vehicles has been studied increasingly in recent years. One of the challenges in this field has been the isolation of EVs from complex biological fluids such as blood. The methods widely used for the isolation process include for example size exclusion chromatography (SEC) and ultracentrifugation (UC). As these methods use size and density of the particle, the have not been efficient enough in isolating EVs from certain particles such as lipoproteins. Due to the challenges related to these methods, other isolation methods have been sought to improve the efficiency of EV isolation. One of these methods is ion-exchange chromatography (IEC). From the two forms of IEC, anion-exchange chromatography has been studied more in EV isolation due to the negative net charge on EV particles. However, in this study the functionality and efficiency of cation-exchange chromatography (CEC) in EV isolation was studied as very little research has been done on this method. In this study, two CEC-resins were studied to define their applicability in EV isolation. A standard strong cation-exchange chromatographic resin SP Sepharose Fast Flow was compared to a strong tentacle-type resin. In addition to this, we studied the possibility to use a magnesium gradient to separate different forms of lipoproteins from EVs through dextran-sulfite precipitation. Tentacle-type CEC-resin was found to be more efficient in capturing EVs compared to the standard-type resin without magnesium. These EVs could then be eluted from the column with sodium chloride. The use of magnesium gradient allowed the separation of apolipoproteins in the samples. Higher concentrations of magnesium also reduced the number of lipoproteins in the samples altogether but resulted in the loss of EVs as well. These results were promising and showed that cation-exchange chromatography can be used in EV isolation. Tentacle-type resin seemed to be most efficient in removing impurities and capturing EVs. While more research is needed before these findings can be applied to clinical use, these results prove that cation-exchange chromatography can be used in EV isolation as a new, efficient and up scalable method.
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(2024)Adoptive cell therapy utilizes the patient's own immunological system in the treatment of cancer. T cells expressing the chimeric antigen receptor (CAR) are produced from the patient's own T-cells. The CAR gene is introduced into the T cells by a gene transfer vector, which results in the T cells expressing the CAR molecule that recognizes the antigen on the surface of the cancer cell. When CAR-T cells are returned to the body, they recognize the cancer cell with the CAR molecule and destroy it. CAR-T cell therapy has shown promising results in the treatment of malignant hematological cancers. The white blood cells used as starting material for CAR-T cells are collected from the patient using a specially designed leukapheresis device. The collected leukapheresis product is transported to the CAR-T cell manufacturing site as soon as possible, either fresh or frozen. The aim of this stability study of leukapheresis products was to determine the effect of storage time and temperature on the quality of fresh cell products regarding cell number, viability and composition. In addition, the goal was to determine the optimal storage temperature and the shelf life of leukapheresis product to ensure high quality cell starting material for CAR-T cell production. The study was performed by dividing the leukapheresis products into two cell bags immediately after collection, one stored at +15–25 °C and the other at +2–8 °C for five days. The leukapheresis products were examined at five different time points (0, 25, 49, 73 and 121 h) for white blood cell count, viability, apoptosis and white blood cell composition. The microbiological purity of the cell products was examined after leukapheresis. The leukocyte composition was stable, viability and cell yield over 80 % for at least 72 hours at +2–8 °C storage temperature. Although small proportions of cells were apoptotic after the 48 hours of storage +2–8 °C, the leukapheresis products contained more than 80 % viable leukocytes after 72 hours and over 70 % after 120 hours. Leukapheresis products remained stable for 48 hours at +15–25 °C, after which their leukocyte composition changed, leukocyte viabilities and yields decreased. The viabilities of the leucocytes were above 90 % for 48 hours at +15–25 °C, but at the 73 h time point, only half of the cells were viable. The optimum storage temperature for leukapheresis products was +2–8 °C, at which white blood cells remained in good quality for 72 hours. These results can be used to set quality requirements for the cell source material of CAR-T cell product and to plan the transport from the collection site of the leukapheresis to the CAR-T cell production site.
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(2024)Tutkimuksen tausta: Avohuollon apteekit tekivät monia toimenpiteitä varmistaakseen apteekkipalveluiden jatkuvuuden ja lääkkeiden saatavuuden COVID-19-pandemian aikana. Kriisijohtamisen prosessiteoria antaa rakenteellisen viitekehyksen kriisien ymmärtämiseen ja hallintaan. Tavoite: Tutkimuksen tavoitteena oli tutkia suomalaisten avohuollon apteekkien kriisijohtamisprosessia COVID-19-pandemian aikana käyttäen kriisijohtamisen teoriaa teoreettisena viitekehyksenä. Menetelmät: Poikkileikkauskyselytutkimus kehitettiin kriisijohtamisen prosessiteorian pohjalta ja lähetettiin suomalaisille avohuollon apteekkareille sekä yliopistoapteekkien johtaville proviisoreille toisen pandemia-aallon aikana loka–marraskuussa 2020. Logistisen regressioanalyysin avulla tutkittiin, oliko johdon riskinäkemyksellä yhteyttä kriisivalmiuteen, ja miten kriisisuunnitelmat, tiimit ja yhteistyö ulkoisten sidosryhmien kanssa olivat yhteydessä pandemian vaikutuksiin avohuollon apteekeissa. Avoimista vastauksista saatu laadullinen aineisto ryhmiteltiin samankaltaisuuksien perusteella. Tulokset: Kyselyyn vastasi yhteensä 221 apteekkaria ja johtavaa proviisoria (vastausprosentti 36,7 %). Apteekeista 79,6 %:lla oli olemassa pandemiasuunnitelma ennen kriisiä. Pandemiakriisitiimi oli nimetty 35,3 %:lla apteekeista ja 33,5 % lisäsi tai paransi yhteistyötä muiden apteekkien tai lääkehuollon toimijoiden kanssa. Kollektiivinen päätöksenteko ja ulkoisen yhteistyön lisääminen tai parantaminen olivat yhteydessä vähäisempiin negatiivisiin vaikutuksiin johdon jaksamisessa. Lisäksi kollektiivinen päätöksenteko oli yhteydessä vähäisempiin negatiivisiin vaikutuksiin organisaation taloudessa. Kirjallisuudesta poiketen olemassa olevalla pandemiasuunnitelmalla oli enemmän negatiivisia vaikutuksia organisaatioiden resursseihin. Yhteyttä apteekkarin riskinäkemyksen ja apteekkien kriisivalmiuden välillä ei havaittu. Johtopäätökset: Apteekkien tekemät toiminnalliset muutokset ja infektion ehkäisy- ja torjuntakäytännöt mahdollistivat keskeisten palvelujen tarjoamisen pandemian asettamista haasteista huolimatta. Oppimista ja sopeutumista tapahtui reaaliajassa kriisin aikana. Kollektiivisen päätöksenteon kehittäminen ja yhteistyö kollegoiden ja muiden lääkehuollon toimijoiden kanssa voivat parantaa apteekkarien jaksamista ja apteekkien taloutta tulevissa kriiseissä. Jatkotutkimuksissa voitaisiin hyödyntää laadullisia tutkimusmenetelmiä ja tutkia tarkemmin kollektiivista päätöksentekoa sekä vaikuttavan kriisisuunnitelman sisältöä avohuollon apteekkien kontekstissa.
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(2024)Antimicrobial resistance (AMR) is a growing global health concern, and the development of new antibacterial agents is crucial to addressing this issue. Commercial antibiotics are not as effective as they used to be to combat infections. Previous studies have demonstrated the promising antimicrobial activity of etrasimod and one of its derivatives, compound 24f, against Gram-positive species. Therefore, as part of this study, we modified the carboxylic acid functional group to produce new derivatives. We synthesized derivatives of etrasimod and 24f, in order to generate a variety of compounds for evaluation of their antimicrobial effectiveness. Furthermore, the study evaluates the compounds' in vitro antibacterial activity and in vivo efficacy using Caenorhabditis elegans worms as an infection model. C. elegans is a widely used model organism in biological research, and it is particularly useful for studying host-pathogen interactions and drug efficacy. In addition, the cytotoxicity on mammalian cells (HeLa) was determined. Compound 18 showed the lowest cytotoxicity level (CC50 = 75.71±14.4 µM) of tested compounds. The antibacterial activity of new etrasimod derivatives was tested against Gram-positive (Staphylococcus aureus, including methicillin-resistant strains (MRSA)) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). The tested compounds showed activity against Gram-positive bacteria but not against any of the Gram-negative strains. Compounds 9 and 18 showed to be the most active compounds, having a minimum inhibitory concentration of 5–6 and 8–10 μM, respectively. Moreover, both compounds showed promising activity in vivo, being able to significantly reduce the bacterial load in infected worms and improve their survival rates in survival experiments. The study provides insights into the development and assessment of potential antibacterial agents, addressing the contemporary challenge of AMR. The study's findings suggest that compounds 9 and 18 could be potential candidates for further development as novel antimicrobial agents.
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(2024)In recent years, animals have been recognized as promising next-generation protein production systems. Animal transgenesis has been achieved primarily in insect cells infected by recombinant baculoviruses. Baculovirus Expression Vector Systems (BEVS) transform the DH10Bac strain of Escherichia coli with the shuttle vector to produce recombinant baculovirus carrying the cargo of interest. The cargo includes at least one promoter driving the expression of at least one protein. PGK is a strong promoter that is naturally active in almost all species where it has been tested, including invertebrates like Drosophila. The PiggyBac transposon-based system is a known strategy for genome integration of foreign genes to create transgenic animals. Nevertheless, nobody has used baculoviruses to deliver genes and produce proteins in earthworms nor to create transgenic earthworms. There is also no information on the sequence of any endogenous E. fetida (earthworm) promoter yet. This project aimed to pilot a novel gene delivery method by creating baculoviruses through the BEVS, carrying the PGK promoter and the GFP reporter gene, and to assess the promoter activity in both Sf9 insect cells and E. fetida through evaluation of GFP fluorescence. Another target was to test the fluorescence after the addition to the baculovirus of the PiggyBac-based inverted terminal repeats (ITRs), flanking the PGK-GFP transcriptional unit. The secondary objective was to develop a non-lethal method for live worm imaging. Conventional restriction enzyme cloning was used to create the shuttle vectors, and restriction digest and Sanger Sequencing were used to identify the positive clones. The Bac-to-Bac BEVS was followed to create baculovirus particles carrying the cargo (PGK-GFP and PGK-GFP-ITR), infect Sf9 insect cells and monitor the PGK activity. Prior to in vitro transfection, the bacmid DNA was confirmed by PCR. These baculoviruses were also used to infect E. fetida and monitor the PGK activity in vivo. E. fetida autofluorescence was assessed before infection. PGK resulted in being much weaker in Sf9 than expected. The flanking of the transcriptional unit of GFP with the ITRs improved the GFP expression. 16% ethanol was shown to anaesthetize E. fetida for 10 to 15 minutes safely. Wild-type and starved E. fetida were shown to have very mild autofluorescence in their digestive system and setae. The coelomic fluid was shown to have strong autofluorescence. Thus, its excretion is crucial before imaging GFP. Likely, all the in vivo fluorescence after infection was due to the worm’s autofluorescence. Therefore, PGK and GFP were unlucky choices for E. fetida.
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