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Browsing by master's degree program "Proviisorin koulutusohjelma"

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  • Ruohonen, Iida (2020)
    Tiivistelmä – Referat – Abstract 15D is a generic, 15-dimensional instrument for measuring health-related quality of life (HRQoL). 15D instrument has been used in multiple studies evaluating the effectiveness of medical interventions in Finland and abroad. 15D-instrument is a self-administered questionnaire traditionally administered in a paper-and-pencil format. With the emergence of novel technologies, electronic modes of delivery of the 15D instrument are becoming increasingly common as methods for data collection. However, there are no previous studies evaluating electronic modes of delivery of the 15D instrument. In previous studies, electronic instruments measuring patient-reported outcomes have shown strong measurement equivalence and high acceptability. The aim of this study is to evaluate acceptability and measurement equivalence of electronic delivery modes of the 15D instrument. A repeated measures, randomized cross-over study was conducted in the Department of Otorhinolaryngology at Helsinki University Hospital during April, May and June of 2019. A total of 160 outpatients who participated in the study were randomized into four groups of 40 patients. Every participant filled two delivery modes of the 15D instrument: a single paper-and-pencil questionnaire and one out of two electronic questionnaires provided in the study. The two electronic delivery modes delivered in the study were a web-based questionnaire and a mobile app-based questionnaire. The order and the mode of the administration varied between the groups. The patients filled the first questionnaire before the doctor’s appointment at the study site. The patients were then asked to fill the second questionnaire after the doctor’s appointment at home within 3 days after the first administration. Information about acceptability concerning different delivery modes were collected using an end-of-study questionnaire. As a part of determining patient acceptability, response rates for different delivery forms and mode preferences were examined. Measurement equivalence was assessed by intra class correlation coefficients (ICCs) and comparison of mean and median for 15D scores and weighted kappa for item scores. Paired observations were also visually analysed with Bland-Altman plots. Subgroup analyses were conducted for identifying differences in observed patient characteristics (age, sex, base-line HRQoL). 86 participants (females 53.5 %; males 46.5 %) aged 18 to 80 (mean ± SD: 48.2 ± 15.7) filled both questionnaires of the 15D instrument resulting in an overall response rate of 54.1%. Response rates for filling both questionnaires were lower in both groups that filled electronic forms at home (41.0 % for mobile app-based and 52.5 % for web-based questionnaires) than in the paper-and-pencil groups (60.0 % and 62.5 %). Overall 74.1 % preferred the electronic delivery mode compared to 16.5 % preferring the paper-and-pencil mode. Statistically significant differences favouring the web-based form over the paper-and-pencil form were observed in the speed of use (p = 0.002) and in the possibility to edit answers (p = 0.018). Similarly, mobile app-based form was favoured over paper-and-pencil group in the possibility to edit answers (p = 0,041). In terms of measurement equivalence for 15D index scores, high association across paper-and-pencil and web-based questionnaires (ICC: 0.910 [Cl 95 % 0.794-0.962] and ICC: 0.935 [Cl 95 % 0.862-0.971]) and high to moderate across paper-and-pencil and mobile app-based questionnaires (ICC: 0.949 [Cl 95 % 0.883-0.978] and ICC: 0.928 [Cl 95 % 0.601-0.980]) were observed. A clinically important and a statistically significant difference in mean 15D scores was identified in the paper-mobile app group. A statistically significant but not clinically important difference in medians was observed in mobile app-paper group with participants returning the second delivery form in time. This study provides strong evidence supporting the use of electronic delivery modes of the 15D instrument regarding measurement equivalence and patient acceptability. However, differences in electronic delivery modes may have an impact on measurement equivalence and representativeness of study participants. In this study, a small sample size and limited data on study participants limit the generalizability of the results. Most effective ways of collecting data electronically concerning all age and patient groups must be identified in future studies. Electronic data collection methods offer many opportunities for utilising HRQoL data. For example, it is important to assess whether HRQoL-instruments can be used as clinical tools in the future.
  • Viinamäki, Emilia (2023)
    Alpha-beta-hydrolase domain containing proteins (ABHD) are involved in lipid metabolism and its regulation in human and animal cells. Approximately 50 of these proteins have been identified and their physiological and pathophysiological functions are still further investigated. ABHD2, ABHD3, ABHD4, ABHD5, ABHD6, ABHD12 and ABHD16 are involved in the metabolism of glycerin esters and phospholipids, in particular lipid mediator 2-arachidonoylglycerol (2-AG) and its metabolites have a significant effect on neuroinflammation via the endocannabinoid system. ABHD12 and ABHD16A were at the center of focus in this thesis as enzymes regulating phosphatidylserine and pro-inflammatory lysophosphatidylserine. In this study, toxicity of five (5) abietane terpene derivatives was tested using mouse E15/16 prenatal cortical neurons, cultured in 96-well plates. There were totally 8 plates cultured in three different batches, 60 cell containing wells per each plate. Wells from each plate were divided into treatment groups of 17, three concentrations of every five compound, control and VEH groups. Those concentrations were 0,1 µM, 1 µM and 10 µM, and for the last two plates 1 µM, 10 µM and 100 µM. Treatment was also separated into three batches like the cell culturing. After treatment, number of living cortical neurons in each treatment groups were counted. For that, cells were treated with immunofluorescent NeuN and DAPI antigens and the fluorescence was imagined with automated microscope. CellProfiler was used to recognize and count the number of living cortical neurons. Immunofluorescent MAP2 antigens were also used but because the shape of MAP2-fluorescing cells, CellProfiler could not recognize them. Intensity of MAP2-fluorescence were measured from those imaged, so the work would not be wasted. One-way ordinary variance analyze ANOVA was carried out for the data to figure out if there were statistically significant results. For compound TAC174, there were several significant results with different concentrations but unfortunately, some results showed signs of toxicity and others improved cell-growth. Some significant results were also found with compounds TAC121, TAC147 and TAD40 showing sings of toxicity, but reliability of those results was questioned. Only one compound, TAC150 was not showing clear toxicity towards mouse cortical neurons, at least with lower concentrations. For conclusion, there were no clear or significant results if these compounds are toxic for cortical neurons. TAC150 showed the least sings of toxicity, therefore it could possibly be considered for further studies in medical field.
  • Antelo, Lauri (2023)
    African medicinal plants have been used to treat symptoms of infection successfully for thousands of years. However, no antimicrobial drugs have been developed from these plants. As antibiotic resistance is increasing rapidly, these traditional African herbal medicines can be an important solution in the fight against antibiotic resistance due to their antimicrobial properties. In this research, various extracts o the leaves of Combretum adenogonium (Combretaceae) and the fruits of Piper cubeba (Piperaceae) and Xylopia aethiopica (Annonaceae) were tested for their growth inhibitory effects against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Extracts were made with methanol, water, hexane, and chloroform. In addition, water and ethyl acetate extracts were separated from an 80 % methanol extract using solvent partition. All the studied plants are used for the treatment of infections and wounds in African traditional medicine. Water was used as extraction solvent since it is commonly used in African folk medicine. Both single solvent technique and sequential extraction were used. The antibacterial effects were screened using agar diffusion and microdilution methods. The interaction between an extract and an antibiotic was measured with a checkerboard method. Time-kill experiments were performed using microdilution and plate count methods. In this study, the chloroform extract of C. adenogonium leaves gave the best inhibitory effect of all studied plants against B. cereus (MIC 78.125 µg/ml). In general, B. cereus was the most susceptible of the selected bacteria against extracts and E. coli was the one with most resistance. Time-kill test showed that the antibacterial efficacy was fairly stable throughout the 24-hour period considered with few exceptions. According to checkerboard results, C. adenogonium chloroform extract and tetracycline appeared to inhibit each other's antibacterial activity against B. cereus. However, only one extract was studied in this study, and it is possible that C. adenogonium contains compounds that would have a potentiating effect on antimicrobials. In general, C. adenogonium extracts were effective against B. cereus. The extracts of P. Cubeba were particularly effective against S. aureus. X aethiopica extracts were equally effective for both B. cereus and S. aureus. Methanol extract X. aethiopica is the only extract studied that gave more than 90% inhibition against P. aeruginosa. Therefore, it could be concluded that X. aethiopica has the broadest activity range of the examined plants.
  • Silén, Heidi (2021)
    Antimicrobial resistance is a growing problem worldwide. It has been shown that more than 70% of the bacteria that cause nosocomial infections are resistant to at least one antibiotic commonly used to treat them. Two concomitant phenomena that aggravate the diarrheal disease situation, especially in developing countries, are general contamination (spread of pathogens due to unclean water, poor sanitation, and malnutrition) and resistant bacterial strains (the adverse consequences of infections increase as infections prolong). According to the WHO, foodborne diseases (FBDs) were estimated to have caused approximately 91 million people to become ill and 137,000 deaths in Africa in 2010. The number is about a third of the deaths caused by FBD worldwide. Diarrhea caused about 70% of the FBD burden. Bacteria that cause food poisoning include Bacillus cereus, Campylobacter jejuni, Clostridium botulinum, Clostridium perfringens, Cronobacter sakazakii, Esherichia coli, Listeria monocytogenes, Salmonella spp., Shigella spp., Staphylococccus aureus and Yersinia enterocolitica, some of which are discussed in more detail in this master’s thesis; antibiotics against which resistance has developed, how bacteria resist antibiotics, and the emergence of resistance in Africa. The antibiotic resistance of bacteria and the mechanisms of resistance against antimicrobial drugs are also discussed shortly. In addition to food poisoning, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus can cause difficult-to-treat infections such as wounds. In addition, this work has first dealt with antimicrobial plant derived compounds in general and their modes of action, and then focused on compounds, fractions and extracts of species of the genera Combretum, Terminalia, Pteleopsis and Anogeissus, as well as their antibacterial effects and uses in traditional medicine. In addition, the antibacterial mechanisms of action of different groups of compounds have been discussed in more detail. This work also deals with the combination studies of some plant extracts, fractions and compounds with antibiotics. Combination studies with antibiotics have generally been studied less than the antibacterial effects alone or the effects of combinations of many plant extracts, as used in African traditional medicine. The experimental part covers, among other things, the preparation and yield determination of crude extracts (water and methanol) as well as the agar diffusion method, the microdilution method, the Time kill tests and the checkerboard method in interaction tests to determine MIC, MBC and FIC values. Due to the Covid 19 pandemic, study results were obtained only by the agar diffusion method against Bacillus cereus. The most antimicrobial extracts were extracts of species of the genus Terminalia.
  • Toivonen, Laura (2021)
    Abstract Faculty: Faculty of Pharmacy Degree programme: Master of Science in Pharmacy Study track: Social pharmacy Author: Laura Toivonen Title: Deficiencies and risks related to medication use management in nursing homes identified by Regional State Administrative Agencies during their inspection visits Level: Master´s thesis Month and year: November 2021 Number of pages: 94+7 (appendice) Keywords: Medication safety, medication use process, nursing home, older adult, risk management, guidelines for safe medication practices Supervisor or supervisors: M.Sc. Pharm, PhD student Suvi Hakoinen, University of Helsinki, Keusote; Professor, PhD Marja Airaksinen, University of Helsinki Where deposited: ethesis.helsinki.fi Additional information: Abstract: Nursing home residents are often characterized by older age, multimorbidity and polypharmacy. Medication safety has become an issue as part of client/patient safety in nursing homes in Finland. Still, little is known about medication safety risks and their management in this care context. The aim of this study was to identify deficiencies and risks associated with medication use management in nursing homes using inspection visits by the Regional State Administrative Agencies (AVIs) as a data source. In addition, the aim was to evaluate what issues the AVI-authorities pay attention to in the medication use management during their inspection visits in nursing homes. The data consisted of the latest inspection reports (n = 24) prepared by the Regional State Administrative Agencies (n = 6) on the basis of their nursing home visits (nursing homes for older people). The data were analysed by deductive content analysis methods. In addition to qualitative documentary analysis, quantitative indicators were used to illustrate the frequency of the risks and deficiencies -observed in different phases in the medication use process to identify phases posing risks most commonly. Reason´s system-based risk management theory was applied as a theoretical framework for the study. A total of 372 deficiencies and risks related to medication use process were identified from the inspection reports (n = 24) of Regional State Administrative Agencies. The largest proportion (58,9 %, n = 219) of the deficiencies and risks concerned the management and quality management of the medication use process. Particularly, deficiencies and risks related to lack and competence of personnel were emphasized. Deficiencies and risks were also identified in the self- assessment guidelines for safe medication practices used in the inspected nursing homes. The second highest number of risk observations (26,9 %, n = 100) was reported for ordering, delivery and storage of medicines. In particular, the deficiencies and risks were reported for the storage and warehousing practices. Reported risk observations in other phases of the medicines use process were rare. This study showed that the medication use process in Finnish nursing homes includes deficiencies and risks endangering the safety of the older nursing home residents. In order to manage the risks, both self-assessment and inspection practices by the authorities need development. One way to improve and harmonize both self-assessment and inspection practices could be use of a comprehensive checklist covering of all the relevant issues required for the safe medication practices in nursing homes. Increasing collaboration with pharmacists could also be a way to improve medication safety in nursing homes.
  • Kärkkäinen, Krista (2021)
    Medication errors due to infusion pump programming errors are common in neonatal intensive care units and often lead to overdoses of medicines. Medication errors can be prevented with dosing limits set into the smart infusion pump drug library. However, alert fatigue caused by unnecessary alarms has been identified to hinder their use. To ensure the benefit of dosing limits as a defence of intravenous medication process, the aim of this study was to define the dosing limits to the drug library for certain high alert medications, and to pilot them in the neonatal intensive care unit. The study was based on the theoretical framework of preventive medication risk management. Based on the results, the suitability of the dosing limits for the use of the unit and the patient group was assessed. This mixed method study employed register-based research methods. The research data consisted of the infusion rate related medication errors (n=21) reported to the HUS HaiPro-system between January 2018 and December 2019 in the HUS Neonatal Intensive Care Unit. The data was analysed qualitatively and quantitatively to describe the infusion rate related errors, and to identify their mechanisms and contributing factors. Based on the identified mechanisms of the errors, simulated test patient cases were developed. Dosing limits were defined by a multidisciplinary expert group for certain high alert medications, and their suitability for preventing medication errors was investigated by programming infusion pumps according to the test patient cases and analysing the pump alerts. Based on the identified mechanisms of infusion rate-related medication errors (n=21) in the HaiPro-reports, 2-, 5-, and 10-fold infusion rates as well as mixing of infusion rates between medicines were established as test patient cases. As a result of the tests (n=226), the infusion pumps did not alert when programming normal infusion rates (n=32) and 73% (n = 70/96) of the erroneous 2-, 5-, and 10-fold infusion rates were prevented. 10-fold infusion rates were inhibited in all cases (n=32). Interference of infusion rates between medicines was prevented in 24% (n=24/98) of the cases. According to this study, significant infusion rate related medication errors can be prevented in the neonatal intensive care unit with the multidisciplinarily defined dosing limits set in the infusion pump drug library. However, they do not prevent all the infusion rate related medication errors alone, and therefore additional defences are needed. In addition to the neonatal intensive care unit, the method used in this study to define and test the dosing limits may be applied in other pediatric units in the future. By using this method, the suitability of the dosing limits for the use of the unit and the patient group can be ensured before integration of the barrier and thereby promote the benefits of its use. The suitability of the dosing limits set into the infusion pump drug library should be assessed again after implementing the defence into the neonatal intensive care unit.
  • Al-Salman, Sahar (2024)
    Alzheimerin taudin riskiä lisää monet tekijät sekä mahdollisesti tietyt lääkkeet. Näiden riskien monitoroinnilla saattaa olla suotuisa vaikutus ennusteeseen. Näin ollen riskiä lisäävät lääkkeet olisi erityisen tärkeää tunnistaa ja lopettaa tai rajoittaa käyttöä korvaamalla muilla lääkeryhmillä tai lääkkeettömillä keinoilla. Pitkäaikaisesti käytössä olleiden lääkkeiden hallittu lopettaminen eli annosten pienentäminen tai lopettaminen vaatii varovaisuutta ja tarkkaa harkintaa, jotta vältytään lopetusoireilta eikä heikennetä elämänlaatua. Tämän Tutkielman tavoitteena oli tutkia, kuinka kognitiivisia haittoja aiheuttavia lääkeaineita voidaan lopettaa hallitusti, jotta vältytään irreversiibeleiltä kognitioon kohdistuvilta haitoilta. Tämä toteutettiin tutkimalla lääkevalmisteiden lakisääteisistä valmisteyhteenvedoista (SmPC), pakkausselosteista ja muista keskeisistä terveydenhuollon ammattilaisille suunnatuista tietolähteistä̈ löytyvää tietoa trisyklisten masennuslääkkeiden ja bentsodiatsepiinien hallitusta lopettamisesta. Tutkimusta varten tarkasteltiin kaikkia Suomessa huhtikuussa 2024 markkinoilla olleita lääkeaineita, joilla on merkittäviä antikolinergisia vaikutuksia. Lisäksi tarkasteltiin tuolloin markkinoilla olleita unilääkkeinä käytettyjä bentsodiatsepiineja. Näistä tutkimukseen sisällytetyt lääkeaineet valittiin sen perusteella, että niiden lopettamisessa tulisi noudattaa varovaisuutta (valittiin trisykliset masennuslääkkeet ja bentsodiatsepiinit). Tutkimus toteutettiin laadullisena sisällönanalyysinä, jossa aineistona käytettiin tutkimukseen valittujen lääkkeiden (amitriptyliini ja nortriptyliini, diatsepaami, oksatsepaami ja loratsepaami) valmisteyhteenvetoja (n = 5), pakkausselosteita (n=5), kansainvälisesti merkittävää hoitosuositusta: 1) American Psychological Association APA: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Yhdysvallat, 2) National Institute for Health and Care Excellence NICE: Depression in Adults: Treatment and Management, 3) NICE: Medicines Associated with Dependence or Withdrawal Symptoms: Safe Prescribing and Withdrawal Management for Adults, 4) The Maudsley: Deprescribing Guidelines Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs, Iso-Britannia sekä yhtä kansallista hoitosuositusta (Suomalainen Lääkäriseura Duodecim: Unettomuus Käypä̈ hoito -suositus). Tiedon määrä, sisältö ja laatu vaihtelivat tietolähteiden välillä. Trisyklisten masennuslääkkeiden hallitusta lopettamisesta löytyi selkeästi vähemmän tietoa kuin bentsodiatsepiinien hallitusta lopettamisesta. NICE:n hoitosuositukset täydensivät toisiaan lääkityksen hallitusta lopettamisesta. APA- ja käypä hoito -ohjeistukset sisälsivät tietoa yleisellä tasolla, mutta eivät sisältäneet yksityiskohtia lääkityksen hallitusta lopettamisesta. Muistin ja kognition kannalta huomattiin, kuinka trisyklisten masennuslääkkeiden valmisteyhteenvedoista ja pakkausselosteista puuttui kokonaan tietoa mahdollisista muistiin tai kognitioon kohdistuvista haitoista. Bentsodiatsepiinien mahdollisista muistiin tai kognitioon kohdistuvista haitoista taas löytyi jonkin verran tietoa, mutta tieto oli suhteellisen rajallista ja epätarkkaa.
  • Silén, Jenna (2021)
    The life cycle of Chlamydia pneumoniae is a biphasic developmental cycle, as a obligate intracellular bacterium, it forms various morphological forms, including elementary bodies, reticulate bodies and aberrant bodies belonging to a persistent form. Due to the bacterial life cycle and the fact that chronication of C. pneumoniae infection and formation of persistent infection as well as pathogenesis is a complex problem involving multiple signaling pathways and affecting several different cells, it is useful to seek medication to influence infection from different stages of the bacterial life cycle. There are several different factors that induce persistence and thus models of persistence. Although the detection of aberrant RBs and thus aberrant bodies in C. pneumoniae infected tissues does not provide complete certainty about chronic infection, the bacterium has been linked to chronic health problems such as atherosclerotic cardiovascular disease and asthma. The aim of the study was to develop a persistence model induced by beta-lactam antibiotics, amoxicillin and penicillin G, in A549 cells by monitoring the size, shape, and number of inclusions using the IPA method and the immunofluorescence staining method for infection. In addition, the antibiotic sensitizing effect of three compounds on pulmonary chlamydial infection was studied. This effect was monitored by examining the recovery of persistent infection and by monitoring the protective effect of the compounds on beta-lactam-induced persistence. The work succeeded in finding an infection model that is well suited for studying beta-lactam persistence. Due to treatment recommendations, pulmonary chlamydial infections are practically treated with beta-lactam antibiotics. Based on the methods used, it was found that amoxicillin concentrations of 10 and 25 µg/ml and penicillin G concentrations of 100 U/ml and 250 U/ml were sufficiently effective to transfer bacteria to a state of persistence. It was found that the amoxicillin persistence model is reversible based on the increase in the size of the inclusions, especially at 25 µg/ml and quantitatively at 10 µg/ml. It was concluded that amoxicillin at a concentration of 10 µg/ml is sufficient to induce persistence in a beta-lactam antibiotic-induced persistence model. Further quantitative studies on the persistence model are needed, such as quantitative PCR based on the OmpA gene to determine more accurate dose-response relationships. Glutathione levels should also be monitored in the persistence model.
  • Peltola, Roosa (2020)
    Amyotrophic lateral sclerosis (ALS) is a rare fatal neurodegenerative disease in which both the upper and lower motor neurons degenerate. Pathological features of the disease include misfolded proteins and accumulations in the central nervous system. The molecular mechanisms of the disease include neuroinflammation, glutamate induced excitotoxicity, and endoplasmic reticulum stress (ER-stress). Numerous genetic defects have been identified in the background of ALS, the most common mutations are in the C9ORF72, SOD1, TDP43 and FUS genes. For each gene mutation, it is important to develop a reliable animal model of ALS for studying pathology and testing new therapies. The most common and most recently found gene mutation, the C9ORF72 repeat expansion mutation, does not yet have an established animal disesase model. The molecular mechanisms of the disease include neuroinflammation, glutamate induced excitotoxicity, and endoplasmic reticulum stress (ER- stress). There is no drug treatment to cure or slow ALS, so the need for new drug therapies that affect the course of the disease is significant. Cerebral dopamine neurotrophic factor (CDNF) protects and restores dopamine neurons and controls ER-stress in preclinical models of Parkinson’s disease. CDNF has also been shown to improve motor coordination as well as protect spinal cord neurons from cell destruction in ALS genetic SOD1- G93A mouse and TDP-43M337 animal models. The purpose of this master's thesis study was to characterize the changes related to neurodegeneration and neuroinflammation in the new C9ORF72-500 disease model and study ER stress of the SOD1-93A disease model and the effect of CDNF on ER stress in SOD1-model and on inflammation in C9-model. In the first sub-study, brain sections from C9ORF72 transgenic and wild-type mice at different time points were subjected to six different immunohistological stainings. The results were compared at each time point (30, 70 and 170) between the wild type and the transgenic group. In another sub-study, spinal cord sections from CDNF snd vehicle treated SOD1- G93A mice were subjected to immunofluorescence staining, after which the intensity of their ER stress marker, GRP78, was analyzed using a confocal microscope. GFAP stained brain sections from CDNF and vehicle treated C9ORF72 mice were analyzed using microscope and imaging analyses. The results of the first sub-study showed neuroinflammation at 24 weeks timepoint in the transgenic group compared to wild-type mice. Pathological features of C9-ALS, various protein accumulations, were observed only in the transgenic group, mainly at 24 weeks. No neuronal loss was observed in this study. The obtained results support the previously published research results and support the reliability of the studied disease model. In the second sub-study ER stress levels were higher in SOD1-mice compared to wild-type mice. Single intracerebroventrical CDNF injection reduced ER stress in SOD1-G93A transgenic mice almost to the same level as ER stress in wild-type mice. CDNF treatment also showed a tendency for reducing inflammation in hippocampus and motor cortex of C9ORF72 mice. The results confirm the pathological role of ER stress in ALS and show that CDNF reduces ER stress when administered as early in the disease as possible, when neuronal damage begins to occur but does not yet lead to neuronal destruction. CDNF appears to be a promising drug candidate for the treatment of ALS and should therefore be further investigated.
  • Seppälä, Katariina (2024)
    General anaesthetics are pharmaceutical agents used to induce general anaesthesia, a reversible state of unconsciousness. Caenorhabditis elegans, a nematode species, has been successfully used as a model organism in the study of gaseous anaesthetics due to its amenability to genetic modification, fully mapped nervous system connectome and high evolutionary conservation. However, C. elegans is less well characterised as a model organism in the study of non-gaseous anaesthetics. The primary aim of the study was to study the potential of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and urethane, a nonselective modulator of various neurotransmitter-gated ion channels, to immobilise C. elegans without activating antioxidant response signalling by transcription factor SKN-1, the nematode orthologue of the mammalian Nrf/CNC proteins. The transparent body of C. elegans enables microscopic imaging of cellular processes, but high-quality imaging requires the immobilisation of the worm. A commonly used chemical immobilising agent, sodium azide, causes SKN-1 activation in C. elegans, which may limit the use of sodium azide in studies on SKN-1 promoters. A secondary aim of this study was to study the impact of ketamine, an activator of mTOR (mechanistic target of rapamycin) signalling, on the lifespan of C. elegans. The lifespan of C. elegans has been found to increase with inhibition of the mTOR homologue pathway in previous studies. Ketamine and urethane were administered to wild-type C. elegans in aqueous media in 96-well plates. Behavioural endpoints of immobility and uncoordination were assessed manually via microscopic observation and video recordings. SKN-1 activation was studied by measuring drug-induced fluorescence in mutant strain CL2166, which carries a green fluorescent protein reporter of SKN-1 downstream target GST-4 (glutathione-S-transferase). A lifespan assay was performed with sterile C. elegans strain SS104 by incorporating ketamine in the worm maintenance agar. In this study, urethane did not appear to be a potent immobilisation agent. Ketamine was found to cause reversible weak immobilisation at a similar concentration at which sodium azide fully paralyses wild-type C. elegans. At lower doses ketamine caused uncoordinated locomotion. Short-term exposure to an immobility-inducing dose of ketamine was not found to significantly activate SKN-1. In the lifespan assay, ketamine unexpectedly appeared to significantly increase the nematode lifespan compared to control treatment.
  • Pykälämäki, Matias (2023)
    Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the death of nigrostriatal dopaminergic neurons and formation of intraneuronal protein aggregates called Lewy bodies and Lewy neurites. These inclusions consist of a protein called α-synuclein (aSyn) but also of other proteins, lipids and cell organelles. Progressive cell death leads to nonmotor and motor symptoms. Current therapies for PD are symptomatic and do not modify the disease progression. Therefore, there is a need for the development of therapies attenuating the neurodegeneration. The pre-formed fibrils (PFF) model enables studying of aSyn aggregation and mechanisms behind inclusion formation. The PFF model is based on the exogenous aSyn fibrils’ tendency to result in formation of Lewy body -like inclusions when added in cell culture or in animals. Primary neuronal cultures of mice and rats have typically been used to model aSyn aggregation in vitro with the PFF model. Primary neuronal cultures provide practicality and are able to depict relevant features of dopaminergic neurons. To gain insight about the composition of E13.5 primary embryonic mouse midbrain culture and to enable adaptation of an existing protocol to study other cell types, this study identified and quantified several relevant cellular phenotypes in the micro island culture. The cells were fixed on day in vitro (DIV) 8 or DIV 22 and analysis was conducted using fluorescent immunocytochemistry combined with automated image analysis software, CellProfiler. On DIV 8, tyrosine hydroxylase -positive dopaminergic neurons represented 5 % of the total cells in the culture. Neuronal nuclear antigen -positive neurons resulted representing 30 % of the total cells. Gabaergic neurons were identified to be abundant in the culture and certain dopaminergic neurons were identified as immunoreactive for GABA. Choline acetyltransferase -positive cholinergic neurons were also identified to be present in the culture. The number of oligodendrocyte precursors (OPCs) was observed to be significantly smaller than the number of dopaminergic neurons. OPCs represented around 1 % of the culture on DIV 8. Glutaminergic neurons, parvalbumin-positive interneurons, microglia or astrocytes were not identified in the culture on DIV 8. The number of astrocytes was observed to increase as the incubation time was prolonged to DIV 22. Overall these findings provide valuable insights of the composition of cell phenotypes in E13.5 mouse midbrain culture. The results also provide additional validation for suitability of the original protocol to robustly produce midbrain dopaminergic cultures with minimal number of glial cells. Understanding more about the relevance and interplay of different cell phenotypes in PD pathophysiology can provide valuable insight for the development of potential therapeutic strategies.
  • Leinoluoto, Otto (2023)
    Diseases of the posterior eye segment, such as age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema and glaucoma are the leading cause of blindness worldwide. Current therapy to treat these vision-threatening diseases relies on intravitreal injections to maintain a desired therapeutic drug concentration in the back of the eye. Frequent intravitreal injections are uncomfortable with poor patient compliance and causes major burden to the healthcare systems as well as to the patients. Small molecule drugs have shorter half-life in the vitreous and are eliminated rapidly. This requires frequent intravitreal dosing intervals that are not feasible in the clinical settings. Also, intravitreally injected small molecule drugs are often poorly and non-specifically distributed to the ocular tissues causing adverse effects. To address these issues, controlled and sustained drug delivery systems in the form of drug conjugates are desirable. Conjugating small molecule drugs with enzymatically cleavable peptide linkers increases the residence time in the vitreous. The peptide linker gets cleaved by vitreal enzyme and the released drug reaches the target in retina and choroid. Aim of this thesis was to screen a library of 25 peptide linkers for cleavage in the presence of porcine vitreal enzymes. The peptide linkers were chemically synthesized and the in vitro stability of the peptide linkers were studied in freshly isolated porcine vitreous. Ten time point samples were collected over a period of 45 days and the peptide cleavage in porcine vitreous was assessed by LC-MS method. A TQ-S liquid chromatography-mass spectrometer was used to study the linker cleavage. LC-MS method development for the peptide library was carried out using IntelliStart wizard function. Out of the 25 peptide linker in the library, stability of eight linkers were not included in the LC-MS analysis as a mass method could not be developed. Out of 17 peptide linkers studied, 14 were categorized as fast cleaving linkers (>90% of the linker cleaved in porcine vitreous after 5 h). Three linker peptides; P4, P5 and P25 were categorized as slow cleaving linkers. Conjugating slow cleaving peptide linkers to small molecule drugs will increase the half-life and enhance the duration of drug action upon intravitreal injection. In this study, linkers that are hydrolyzed by specific enzymes present in vitreous or ocular tissues are exploited to investigate their potential for delivering small molecule drugs.
  • Kainulainen, Saila (2020)
    The solubility of a poorly water-soluble drug can be improved by converting the crystalline drug into an amorphous form. However, the amorphous form is metastable due to the higher energy state and recrystallization may occur during storage and dissolution. The amorphous form can be stabilized by forming an amorphous solid dispersion (ASD), where the drug molecules are dispersed to the solid medium, e.g. hydrophilic polymer. One preparation method for amorphous solid dispersions is spray drying, where a solution containing a drug and polymer is converted into small droplets in a drying chamber, in which the solvent evaporates in a hot gas stream and solid particles are formed. The aim of this study was to investigate whether an ASD of a poorly water-soluble drug can be prepared by spray drying using 20:80 (V/V) ethanol-water mixture as a solvent in a feed solution. Indomethacin (γ-polymorph) was used as a model drug and polyvinylpyrrolidone vinyl acetate (PVPVA) as a polymer. The aim was to find a suitable formulation where the drug is in the amorphous form after spray drying and remains in the amorphous form during storage. The ratios of the drug to polymer in the spray-dried formulations were 1:4, 1:6, 1:8, 1:10, 1:12 and 1:16. The study also examined whether a change in one process parameter, pump feed rate, affects the amorphous nature and stability of the resulting spray-dried solid dispersions. Two different pump feed rates, a higher 30% and a lower 15%, were used in the study. X-ray powder diffraction (XRPD) was used to characterize the solid-state of the spray-dried formulations. XRPD measurements were performed immediately after spray drying and on selected time points during storage. Formulations 1:10 at 30% feed rate, 1:12 at both feed rates and 1:16 at 30% feed rate were amorphous after spray drying. In 1:12 (30%) and 1:16 (30%) formulations indomethacin remained in amorphous form over the study periods (22 and 56 days, respectively). In other formulations, indomethacin was found to be in crystalline α-form immediately after spray drying or recrystallization to the α-form occurred during storage. The interaction between indomethacin and PVPVA was studied by surface plasmon resonance spectroscopy (SPR). The aim of the SPR measurements was to understand the interaction between these substances in the feed solution used in spray drying. PVPVA solutions of various concentrations (1%, 0.5%, 0.1% and 0.01%) were injected to the surface of the gold sensor coated with crystalline γ-indomethacin, and the changes in the SPR signal responses were monitored during the interaction. The same measurements were also performed on a pure gold sensor without indomethacin. An interaction between indomethacin and PVPVA can be observed, and based on the measurements, a polymer layer with a thickness of about 1 nm was formed on the surface of the indomethacin sensor regardless of the concentration of the polymer solution. Thus, even a small amount of polymer in solution is sufficient to cover the indomethacin crystals. This may also occur in the feed solution during spray drying, but further studies with SPR are still needed, especially with amorphous indomethacin. This study showed that an ASD of indomethacin and PVPVA can be successfully prepared by spray drying using an aqueous feed solution. Spray-dried 1:12 and 1:16 formulations at a higher pump feed rate were found to be stable enough for further studies. If the spray-dried material is further formulated into a pharmaceutical product, indomethacin must remain in amorphous form throughout the shelf-life of the product to maintain the improved solubility.
  • Rautiainen, Swarna (2020)
    Endothelial dysfunction is a common characteristic of several diseases including diabetes mellitus, coronary heart disease and stroke. Healthy endothelium ensures vascular homeostasis, regulation of blood flow and the exchange of oxygen and nutrients, as well as immune cell filtration to the surrounding tissues. In many cases, endothelial dysfunction results in ischemia in the surrounding tissues impairing cellular regeneration mechanisms, which can lead to tissue necrosis in the worst case. Therapeutic angiogenesis via stem cell transplantation aims to restore tissue blood flow and thus aid in tissue regeneration and restoration of a functioning tissue. Adipose derived stem/stromal cells (ASC) are a stem cell population with a multilineage differentiation ability. They have been shown to differentiate towards adipogenic, osteogenic, chondrogenic, myogenic and neurogenic lineages among others. Their easy obtainability from liposuction material and abundance in the adipose tissue makes them an especially practical and favorable cell option for stem cell research. In angiogenesis research, ASCs are commonly used in a co-culture with an endothelial cell (EC) type such as human umbilical vein endothelial cell. ASCs secrete extracellular vesicles (EV) that are small membrane bound vesicles with a diameter ranging from 40-1000 nm, and which have the ability to alter the behavior of target cells through their cargo. EV cargo consists of microRNAs, messenger-RNAs and proteins, and the EV cargo of ASCs has been shown to have proangiogenic effects. The aim of this work was to review what is currently known about ASC ability to promote angiogenesis through paracrine secretion and differentiation into endothelial cells or pericytes, interactions between ASCs and endothelial cells in the angiogenesis promoting process and the role of ASC extracellular vesicles in promoting angiogenesis. The methods for this work were database research of related articles using scientific databases and search engines, article categorization and reading, and finally manuscript production. It can be concluded from the current literature that a co-culture environment of ASCs and an endothelial cell type supports the formation of tube-like structures in vitro. Additional insulin like growth factor 1 in culture medium enhances the expression of angiogenesis-related growth factors in both cell types via PI3K/AKT signaling pathway. Further, the activation of platelet derived growth factor receptor β supports ASC ability to promote vascular network formation. On the contrary, the presence of ASC secreted activin A results in the inhibition of vascular network formation. ASCs can differentiate into endothelial cells particularly in three-dimensional culture conditions. In addition, fibroblast growth factor 2 and the activation of the AKT-pathway are crucial for endothelial differentiation. In addition, ASCs have the ability to differentiate into pericytes and assume a stabilizing role on the outside of the microvessels. Concerning ASC derived EVs and their cargo, miR-31, miR-125a and miR-126 have proangiogenic effects in vitro and in vivo. Proangiogenic miRNAs in ASC EV cargo are miR-181b-5p and the let7-family, out of which miR-181b-5p upregulates vascular endothelial growth factor and hypoxia-inducible factor 1α and let7-family influences tube formation ability of ECs. In vivo, ASC derived EVs support fat grafting, enhance wound healing both in healthy and diabetic environment, and provide cardioprotection. Therefore, ASC EVs show potential for therapeutic angiogenesis but currently there is a lack of clinical trials in EV research.
  • Eronen, Sini-Tuulia (2022)
    Introduction: When people age, the composition of sleep changes and sleep becomes more sensitive to external disturbances, making insomnia also more common. Medication is not the first-line treatment option for insomnia. Benzodiazepines or benzodiazepine receptor agonists for the treatment of insomnia have been in the focus of past studies. The content of the dosing instructions for the supplied medicines has not been studied. The dosing instructions should provide clear instructions on how to dose the medicine prescribed to the patient. The aim of this study was to investigate the content and quality of dosing instructions prescribed for the treatment of insomnia for Finns aged ≥75 years in 2020 based on the prospective reimbursement register data by the Social Insurance Institution of Finland (Kela). Materials and methods: The reimbursed purchases of all medicines by persons aged ≥75 years from 1.1.2020 to 31.12.2020 were selected by ATC code from the medicines data according to the Insomnia: Current Care guidelines. The data was gathered from Kela’s dispensations reimbursed under the National Health Insurance scheme. The dataset consisted of 1,080,843 delivery lines, which were screened, and 328,285 lines were included in the analyses. Dosage instructions were reviewed according to the following predetermined five categories: frequency of use, dose, timing, warnings or remarks, and inappropriate instructions. In addition, 1000 dosing instructions were randomly derived to study the phrasing and appropriateness of the dosing instructions in more detail. Results: In 2020, an average of 3.8 reimbursed hypnotic drug deliveries were made per elderly person. Of the deliveries, 68% were for women. 52% of drug deliveries were partially made later and not by original prescription. In the hypnotic dataset, the three most administered drugs were zopiclone (41%), mirtazapine (34%) and zolpidem (12%). The dosage was prescribed in 98–99% of the dosage instructions. Dosing schedule was reported in 83% of dosing instructions and regularity of use was reported in 57% of them. Only 3-6% of the dosing instructions had comments or warnings. 1–2% of the dosing instructions were vague. The duration or regularity of use was clearly indicated in 5% of the dosing instructions. Only 0.1% of dosage instructions contained instructions for discontinuation or reduction. Discussion: The dose and timing of administration were well reported, but the frequency of use was reported in only about half of the dosing instructions. Only few dosing instructions contained remarks or warnings even though hypnotics are at risk for the elderly. Among the three most administered drugs for the treatment of insomnia were two benzodiazepine receptor agonists, zopiclone and zolpidem. However, they may not be suitable for the elderly according to Beers criteria and their use should be avoided. During 2020, an average of four drug deliveries were made per elderly person for the treatment of insomnia, which may indicate prolonged hypnotics use. In addition, more than half of the deliveries were partially made later and not by original prescription. Thus, several drug packages are prescribed for prescriptions, although the drug-based treatment of insomnia should only be short-lived. Conclusions: There are significant deficiencies in the contents and quality in the dosing instructions for drugs delivered to the elderly for insomnia. Minimum information on dose, timing and duration of use was not found in all dosing instructions in this study. Understandable dosing instructions and the reduction in the amount of medication in the prescription could have a further effect on reducing the long-term use of hypnotics, also increasing the safety of medicine use in the elderly.
  • Hou, Kathy (2021)
    Antidepressant use among children and adolescents has become more common in many countries. The prevalence of antidepressants is higher for boys but during adolescence girls’ have a higher antidepressant prevalence. In previous studies, the prevalence of selective serotonin re-uptake inhibitors (SSRI) has increased. The aim of this study was to investigate antidepressant use among Finnish children and adolescents aged 1–17 years during 2008–2019. The differences of antidepressant use in different age groups and genders were investigated. Furthermore, the secondary objective was to examine the trends in prevalence and costs of the five most commonly used antidepressant agents. This was a nation-wide register study. The data for this study was from Kelasto which is a statistical database maintained by the Social Insurance Institution of Finland. The extracted data was from 2008–2018 and included each persons’ age, gender, dispensed drug and costs. The data extracted was for 1–17-year-olds who had been dispensed reimbursed antidepressants from community pharmacies. The data was analyzed with Microsoft Office’s Excel program. The results were transferred in to tables and reported as prevalences by age groups, genders, antidepressants and costs. The prevalence of antidepressant use among children and adolescents was 5,0 per 1000 in 2008 and it increased to 10,3 by 2018. In the youngest age group of 1–6-year-olds, antidepressant use decreased. Antidepressant use increased slightly among 7–12-year-olds. Antidepressant use increased the most among 13–17-year-olds. 13–17-year-old girls had the higher antidepressant use prevalence throughout the study. The same group had a 2,4-fold increase in prevalence during the study period which accounted for the biggest increase in the study. The most used group of antidepressants was SSRIs. The total cost for antidepressants among children and adolescents increased by 73,7 % during the study period. The most commonly used antidepressant agents were fluoxetine, sertraline, escitalopram, mirtazapine, and venlafaxine, respectively. Fluoxetine was the most used agent throughout the study. In 2014, sertraline surpassed escitalopram and became the second most used antidepressant agent. Escitalopram and venlafaxine’s cost per user decreased during the study. The cost per user stayed stable for mirtazapine. Fluoxetine and sertraline’s cost per user increased. The Kelasto database does not include data on indications for prescriptions. The prevalence of antidepressants does not necessarily correlate directly to depression among children and adolescents because antidepressants can be used to treat other diseases. More studies need to be conducted on different off-label uses for antidepressants among children and adolescents. This study only investigated the trends on cost for the five most commonly used antidepressants. Further studies on antidepressant costs among children and adolescents are needed. Additionally, it is essential to investigate the reasons for the increase in antidepressant use among children and adolescents.
  • Hämäläinen, Klaus (2022)
    Multiple Sclerosis (MS) is an incurable autoimmune demyelinating disease affecting the central nervous system (CNS). Although the detailed pathogenesis remains unclear, recent research has highlighted the involvement of B cells. For decades, however, MS research was based on T cell-focused animal models of autoimmune encephalomyelitis (EAE), which do not reflect the involvement of B cells in the pathogenesis. Therefore, B cell-dependent EAE models are hypothesized to allow a better understanding of MS immunohistopathology and may therefore lead to the development of efficient treatments. In our spontaneous relapsing-remitting (RR) EAE model, B cells are recruited from the endogenous repertoire by transgenic myelin oligodendrocyte glycoprotein (MOG) -reactive T cells, causing the development of EAE in 3–4-month-old mice. Interestingly, MOG-specific antibodies are present long before actual onset of clinical disease and can be detected already in 5-week-old RR mice and disease development in RR mice is dependent both on the presence of (presumably MOG-specific) B cells as well as on stimuli provided by intestinal microbiota. Firstly, we evaluated the broader usability of induced germinal center cell (iGB) culture as a model for B cell repertoire studies. Then, by using iGB culture, we studied whether MOG-specific B cells are present in secondary lymphoid organs of younger than 4-week-old and germ-free RR mice. Finally, this study aimed to investigate whether the repertoire of MOG-specific B cells undergoes significant qualitative changes from young healthy mice to older acutely sick RR mice, and whether at the time of disease onset the recruited MOG-specific B cells expand and mature in the cervical nodes (cLN) or in the CNS. To do so, following the hosting-lab’s previous single-cell RNA sequencing (scRNA-seq) of B cells derived from cLN of 5-week-old RR mice, we performed the scRNA-seq of B cells from CNS, spleen, and cLN of acutely sick RR EAE mice. We demonstrated that iGB culture is an unsuitable tool to expand pre-activated B cells, and hence, in our hands it was inappropriate for repertoire studies. However, iGB culture proved to be useful for screening different organs for MOG-specific B lymphocytes, and we found that anti-MOG antibodies were firstly detected in 3-4-week-old RR mice, and MOG-specific B cells were present also in germ-free RR mice. Our scRNA-seq results revealed many highly expanded MOG-specific B cell clonotypes in acutely sick RR mice. Moreover, the B cell repertoire of sick RR mice was more diverse, including IgG1, IgM, IgG2b, IgG2c, and IgG3 isotypes, compared to healthy 5-week-old RR mice that had only IgG1 or IgM isotypes. Two-thirds of the expanded clonotypes were primarily detected in the CNS in sick RR mice, indicating that clonotypes develop further and continue isotype switching within the CNS. We also detected more somatic mutation in the variable region of expanded clones of sick RR mice compared to 5-week-old RR mice. The results of this study clearly show an antigen-driven evolution of the MOG-specific B cell repertoire from healthy young to acutely sick RR mice, which seems to occur mainly in CNS itself. In contrast, cLN are the major initial priming site of MOG-specific B cells in healthy RR mice, even under germ-free conditions. This suggests that commensal microbiota is not required for initial recruitment of MOG-specific B cells, but for the development of EAE. To further validate our encouraging scRNA-Seq results, it is necessary, in future experiments, to confirm the MOG-specificity of expanded clonotypes.
  • Mönkkönen, Iina (2024)
    Lääkityspoikkeamat aiheuttavat maailmanlaajuisesti eniten vältettävissä olevia potilashaittoja terveydenhuollossa. Vaaratapahtumista raportoiminen on tärkeää lääkitysturvallisuuden edistämiseksi, sillä raportoinnin avulla saadaan tietoa lääkehoitoprosessin riskikohdista, jota voidaan puolestaan hyödyntää kehitettäessä lääkehoitoprosessien suojauksia. Tutkimuksen tavoitteena oli selvittää, millaisia sosiaali- ja terveydenhuollossa tapahtuneita lääkehoidon vaaratapahtumia apteekeissa on havaittu ja estetty sekä millaisiin kehittämistoimenpiteisiin apteekkien vaaratapahtumailmoitukset johtivat tapahtumayksiköissä. Tutkimus toteutettiin retrospektiivisenä rekisteripohjaisena tutkimuksena avoapteekkien sosiaali- ja terveydenhuollon yksiköihin lähettämistä HaiPro-vaaratapahtumailmoituksista sekä tapahtumayksiköiden seurantalomakkeista. Tutkimusaineisto oli kerätty Pohjanmaan, Kanta-Hämeen ja Keski-Uudenmaan hyvinvointialueilla 1.2.2022-31.12.2023. Alkuperäinen aineisto sisälsi 457 vaaratapahtumailmoitusta. Aineiston esikäsittelyssä poistettiin ilmoitukset, jotka eivät olleet sosiaali- ja terveydenhuollossa tapahtuneita vaaratapahtumia (n=11). Ilmoitukset, jotka koskivat useampaa kuin yhtä lääkeainetta tai potilasta (n=15) jaettiin erillisiksi tapauksiksi. Strukturoitujen kohtien valintojen oikeellisuus tarkistettiin tapahtumakuvausten perusteella ja tarvittaessa valinta korjattiin. Lopulliselle tutkimusaineistolle (n=461) suoritettiin kuvaileva määrällinen analyysi (frekvenssit ja prosenttiosuudet) Microsoft Excel ohjelmistolla. Aineistosta laskettiin vaaratapahtumien määrä, luonne, havaitsija, tyyppi sekä asiakkaalle ja apteekille aiheutuneet seuraukset, yleisimmin esiintyneet lääkeaineet, lääkeaineryhmät sekä suuren riskin lääkkeiden osuus. Terveydenhuollon yksiköiden kehittämistoimenpiteille suoritettiin laadullinen sisällönanalyysi aineistolähtöisesti sekä tarkasteltiin kehittämistoimenpiteiden jakautumista yksilö- ja järjestelmänäkökulmiin. Lähes kaikki (94 %) aineiston vaaratapahtumista (n=461) oli apteekin havaitsemia. Valtaosa tapauksista oli läheltä piti -tapahtumia (71 %). Vaaratapahtumat olivat lähes aina lääkehoitoon liittyviä (98 %). Yleisimmin kyseessä oli määräyspoikkeama (93 %), jossa oli väärä annos tai vahvuus (26 %), epäselvä tai puutteellinen annosohje (13 %) tai SIC-merkintä puuttui (11 %). Eniten vaaratapahtumailmoituksia oli hermostoon vaikuttavista lääkeaineista (23 %) sekä systeemisesti vaikuttavista infektiolääkkeistä (19 %). Suurin osa sosiaali- ja terveydenhuollossa ehdotetuista kehittämistoimenpiteistä (n=470) oli tapahtuman käsittelyä ja siitä keskustelua (63 %). Yleisimmin ehdotettiin asian käsittelyä tai siitä keskustelua ylilääkärin ja lääkäreiden kanssa (15 %) tai moniammatillisessa palaverissa (14 %). Tämä tutkimus osoittaa apteekin roolin keskeisen merkityksen sosiaali- ja terveydenhuollon toimijana ja lääkitysturvallisuuden varmistajana. Tutkimuksen perusteella apteekkien vaaratapahtumailmoittaminen voi tukea muun sosiaali- ja terveydenhuollon lääkehoitoprosessien turvallisuuden kehittämistä, mutta kehittämistoimien vaikuttavuutta lääkehoidon vaaratapahtumien ilmaantumiseen tulisi tutkia lisää.
  • Mannermaa, Siiri (2023)
    Medication safety is an important target of development in health and social services systems internationally. Medication errors are one of the biggest risk factors in medication safety. Majority of the medication incidents could be avoided by improving the medication treatment process. Patient safety incident reporting systems enable health and social services to collect systematic data from risk factors within the medication treatment process. This study was conducted as a retrospective registry-based study where medication incidents that occurred in health and social care units reported by community pharmacies to the incident reporting system HaiPro from 21st of September 2021 to 31st of October 2022 were analysed. Cases that did not meet the criteria for this study (n=55) were removed from the original data (n=3841). If needed, the nature and type of the reported error were corrected. A descriptive quantitative analysis was conducted for the final data (n=3786) using Microsoft Excel. The number, natures, types, observers, and prescription types of medication errors were investigated from the data. In addition, the most common groups of medicinal substance and high risk medicines were identified. A qualitive content analysis was performed to near miss cases involving high-risk medications (n=446) using the Atlas.ti program. Interventions, measures following the interventions and risks prevented by the measures were identified from the open description in the incident reports. The qualitative analysis was performed as an abductive content analysis. Of the medication errors included in the study (n=3786) 91% were detected by community pharmacies and the majority (68%) of the reported incidents were near misses. Most (96%) of the safety incidents (n=3786) were associated with the patient’s medication treatment and had occurred mostly during the prescribing process (92%). As a result from the prescribing errors, patients were most commonly prescribed wrong dose or strength of the medicine (26%) or the prescription lacked SIC marking (26%). High-risk medications occurred in 16% (n=591) of the incidents (n=3786). Most frequently detected high-risk medications were opioids (35 %). Three quarters (76 %) of safety incidents associated with high-risk medications were near misses (n=446). The majority (92 %) of interventions (n=471) made to prevent safety incidents associated with high-risk medications were made by community pharmacies. The most frequent intervention was community pharmacies contacting the doctor. Based on the HaiPro incident reports made about medication errors in health and social care units reported by community pharmacies, it can be concluded that community pharmacies are a central barrier in primary care medication treatment process. Community pharmacies detect and report medication errors that have occurred in other health and social care units. Safety incidents reported by pharmacies systematically accumulate important information that can be used in the development of medication safety in primary care at a unit, wellbeing services county and national levels.
  • Laakso, Johanna (2022)
    The operation of community pharmacies has developed extensively over the past decades, with special emphasis on medication counselling services. In addition to dispensing, pharmacies can offer various kinds of clinical pharmacy services, such as medication reviews, automated dose dispensing and other services to support rational use of medicines. All this activity requires patient information, which is currently available in pharmacies only from prescriptions, reimbursement information, and by asking the customer. Because of this, a need to increase the availability of patient information in pharmacies has come up. The aim of this study was to determine what kind of patient information should be available in community pharmacies for 1) the statutory dispensing of medicines, the medication counselling and treatment monitoring, and 2) other services related to promotion of health and well-being and prevention of diseases. Furthermore, the study investigated experts' experiences of the sufficiency of patient information in pharmacies, as well as in what form and from what period the information should be available in pharmacies. The study was conducted as a 3-round Delphi study with an expert panel consisting of 20 pharmacists specialized in clinical pharmacy. Consensus was formed with the help of a preliminary patient information list which had been compiled based on the literature and the expertise of the research group (a total of 39 patient data items). The limit of the experts' consensus was set to ≥80%. The Delphi-rounds were conducted as electronic surveys during the spring and summer of 2022. The responses were analysed using quantitative and qualitative methods. Most of the expert panellists (n=20) perceived that the patient information available in community pharmacies was insufficient. This study reached a strong consensus that pharmacies should have quite a large set of patient information available both for dispensing medicines and medication counselling, and for providing services supporting rational use of medicines. Of the patient data items, nine reached the consensus line concerning dispensing of medicines and 31 measures concerning other services. From both points of view, information about the client's diagnoses, blood pressure, and the GFR value indicating kidney function were rated as the most important to be available in community pharmacies. However, the panellists also reported challenges to overcome in the access and utilization of the patient information, for example, related to current legislation, resources, and competences of pharmacists. These aspects should be considered in the development of community pharmacy practice and electronic patient information (e.g., Kanta services).