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  • Heikura, Veera (2023)
    Solids most commonly come in two broad forms: crystalline or amorphous. Crystalline solids have a regular, organized long-range structure of atoms and crystals, and are characterized by having a distinct shape, specific volume, and melting point. They can also have multiple polymorphs. On the other hand, amorphous solids do not usually have a regular long-range atomic and crystal structure and their molecules are more easily separated, which makes them more soluble in their surroundings compared to crystalline solids. However, despite this, short-range order can also occur. To improve the solubility of crystalline solids, co-amorphous systems can be created by mixing together two or more chemically different compounds in a way that they don't form a regular crystalline structure, but rather an irregular, amorphous one. Co-amorphous systems can be analyzed qualitatively or quantitatively. Qualitative analysis is often the main focus when studying amorphous matter, as it can be difficult to accurately quantify these materials using techniques based on crystal structures. Additionally, many amorphous systems are made up of complex mixtures of polymers with different chemical and physical properties. This study aimed to determine the most effective method for obtaining quantitative information about the co-amorphization of indomethacin and tryptophan. Three analytical techniques were used for this purpose: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Raman spectroscopy. The co-amorphous system was created by mixing together α-indomethacin and tryptophan, γ-indomethacin and tryptophan, and amorphous indomethacin and tryptophan. This study showed that DSC, XRPD, and Raman spectroscopy are effective in providing quantitative information about crystallinity and crystal size. These techniques were able to accurately detect and characterize discrete residual crystals, and were able to measure and quantify the amount of these substances. Even though these methods may not be able to detect nanoscale structures with precision, they still provided valuable information about the crystalline and amorphous nature of the samples studied. Additionally, the fact that similar quantitative results were obtained using different analysis methods further supports the reliability of these techniques. Of all the techniques discussed, Raman spectroscopy was able to identify even small residual crystals, resulting in the highest calculated crystallinity percentage.
  • Rauvala, Oskari (2023)
    Rodent studies indicate that the effects of pharmacological antidepressant treatments depend on the TrkB (tropomyosin-related kinase B) receptor of the neurotrophic factor BDNF (brain-derived neurotrophic factor). However, the mechanism by which TrkB signaling becomes active remains disputed. Our group proposes that the activation of TrkB signaling is a result of an indirect physiological adaptation to the drug treatment, which is supported by observations made with rapid-acting antidepressants ketamine and nitrous oxide. Previous studies indicate that the immediate effects of the drugs are followed by a sedative state resembling deep sleep, during which TrkB signaling becomes active. The sedative state is accompanied with a drop in core body temperature, and preliminary findings indicate that preventing the drug-induced hypothermia blocks TrkB signaling in the cortex.    The purpose of this study was to investigate the effect of ambient temperature on TrkB signaling in the hippocampus following nitrous oxide administration. Nitrous oxide (65 % ad 100 % O2) was administered to adult male mice for 20 minutes. After the drug treatment the animals were kept in different recovery conditions: room temperature or a heightened ambient temperature of approximately 36 °C for 15 minutes. Following the recovery, the animals were euthanised, and hippocampus samples were collected from the animals. Levels of BDNF and TrkB signaling were analysed with ELISA and western blot, respectively.    Nitrous oxide caused a significant drop in core body temperature, but this was not accompanied with increased BDNF levels or TrkB signaling. Evidence suggests that hippocampal atrophy contributes to depression, but the acute effects of antidepressant treatments on TrkB signaling in this brain area appear to be less pronounced than those seen in the prefrontal cortex. The findings indicate that nitrous oxide has a replicable hypothermic effect, but this is not associated with increased TrkB signaling in the hippocampus.
  • Keskimäki, Sanne (2023)
    Plasmidit ovat geneettisiä elementtejä, joita voidaan käyttää esimerkiksi geeninsiirtovektoreina. Transposonit ovat DNA-fragmentteja, joilla on kyky siirtyä genomissa paikasta toiseen. Tutkimuksessa käytettävä transposoni on piggyBac, joka on eristetty tupsumetalliyökkösen (Trichoplusia ni) soluista. Transpositiossa piggyBac tunnistaa ITR-osat (käännetty terminaalinen toistojakso) siirtäen osien välissä olevan DNA:n. Tutkimuksen tavoitteena oli tuottaa kaksi erilaista plasmidia. pAc5.1-piggyBac-plasmidiin sisällytettiin piggyBac ja pMT-In-EGFP-PB-ITR-plasmidiin ITR-osat sekä niiden väliin hygromysiiniresistenssigeeni sekä EGFP-geeni. BTI-Tn-5B1-4-solujen DNA:sta eristettiin piggyBac sekä ITR-osat ja ne siirrettiin plasmidiin pTOPO-piggyBac-R. Tästä plasmidista irrotettiin erilleen piggyBac ja ITR-osat, joista välivaiheiden kautta rakennettiin lopulliset plasmidit. Plasmidit rakennettiin pitkälti pilkkomalla DNA-fragmentteja restriktioentsyymeillä ja yhdistämällä niitä ligaatiolla. Plasmideja tuotettiin suurempia määriä siirtämällä niitä transformaation avulla E.Coli-soluihin lämpöshokkimenetelmällä ja eristämällä tämän jälkeen saadut plasmidit. Tuotettujen plasmidien onnistuminen varmistettiin pilkkomalla ne restriktioentsyymeillä ja tutkimalla DNA-fragmenttien kokoa agaroosigeelielektroforeesilla. Plasmidinäytteet myös sekvensoitiin osittain. Banaanikärpäsen (Drosophila melanogaster) S2-solut transfektoitiin kehitetyillä plasmideilla ja solukonsentraatioita sekä elinkelpoisuutta mitattiin 8 päivän ajan transfektion jälkeen. Tavoitteena oli hyödyntää EGFP-geeniä fluoresenssimittauksiin. Solunäytteisiin lisättiin kokeen aikana hygromysiini, jotta voitiin selvittää, olivatko viljellyt solut saavuttaneet hygromysiiniresistenssin. Tutkimuksen tuloksena plasmidit saatiin kehitettyä, mutta solukokeiden tulokset jäivät epäselviksi. Solunäytteissä ilmeni kasvatuksen aikana kontaminaatioita. Lisäksi EGFP-osia ei voitu luotettavasti mitata käytössä olleella laitteella. Transfektio tulee siis toistaa transposonisysteemin toiminnan tutkimiseksi. Lisäkokeilla voidaan selvittää tarkemmin kehitetyn transposonisysteemin mahdollisuuksia sekä toiminnan yksityiskohtia.
  • Monni, Reetta (2022)
    Safety of pharmacotherapies is an essential part of patient safety that promotes and supports rational use of medicines. Safety of pharmacotherapies can be divided into two areas; Drug safety and medication safety. Drug safety refers to the safety of a medicine as a product, such as the pharmacological properties and the quality of the manufacturing process. Medication safety ensures the safety of a drug therapy process preventing patients from harm during the course of using medicines. Significant inconsistencies have been identified in the terminology related to drug and medication safety. Challenges to terminology are posed by varying synonyms, ambiguity or overlap of concepts, and misclassification of events in the scientific literature. The primary objective of this study was to scope recent peer-reviewed literature related to the drug safety and medication safety terminology from the period pf 2010-2022. A secondary objective was to examine the relationship between the concepts as presented in the literature, including overlaps and differences between the terms. The study was conducted as a scoping review by using Scopus and Ovid Medline databases. The literature search covered studies from January 2010 to January 2022. The search was conducted by using the following phrases; "("medication safety" OR "drug safety" OR pharmacovigilance) W/5 (definition* OR terminology*)" in Scopus and "("medication safety" OR "drug safety" OR pharmacovigilance) ADJ/6 (definition* OR terminology*)" in Ovid Medline. The references of the included articles were reviewed for any additional material. The relevant material was selected by two researchers. A total of 71 articles were identified from the databases, of which two articles met the predefined inclusion criteria. In addition, one article was included in the study from outside the actual search. Two of the included articles were based on drug safety terminology whereas one article was based on medication safety terminology. The results revealed that there is still a considerable heterogeneity of the terms in the literature. The literature shows several terms and definitions for the same phenomenon and no noticeable consistency in the terms. It would be important to define what a uniform and systematically used terminology would require and to establish a commonly accepted guidelines for its use.
  • 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.
  • 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.
  • Korventausta, Susanna (2022)
    Etätyö yleistyi maaliskuussa 2020 äkillisesti COVID-19 pandemian seurauksena maailman terveysjärjestö WHO:n suosituksesta. Etätyö on ollut ennen koronapandemiaa harvinaista lääketeollisuudessa, joten etätyötä lääketeollisuudessa on tutkittu hyvin vähän. Etätyön on arvioitu jäävän pysyväksi ratkaisuksi, joten on ajankohtaista tutkia etätyön soveltuvuutta ja tehokkuutta lääketeollisuudessa. Etätyöntekijöiden tuottavuus kasvaa yleensä huomattavasti. Työpaikalla koetaan jatkuvasti keskeytyksiä, melua ja muita häiriötekijöitä, joiden lisäksi työmatkat kuormittavat työntekijöitä. Etätyöntekijät säästyvät suurimmalta osalta näistä ongelmista, jolloin suurempi osa heidän työpäivästään kuluu varsinaiseen työntekoon. Valtaosa etätyöntekijöistä tekee etätyötä osan työajastaan. Tutkimuksen tavoitteena oli selvittää kokemuksia etätyöstä, etätyön soveltuvuutta ja etätyön tehokkuuteen vaikuttavia tekijöitä lääketeollisuudessa. Tutkimus on toteutettu Orion Oyj:n Suomen toimipisteissä. Tutkimuksen toteuttamistapa oli kvantitatiivisen ja kvalitatiivisen kyselytutkimuksen yhdistelmä. Yhdistämällä kvantitatiivisia ja kvalitatiivisia kysymyksiä pyrittiin saamaan tarkempia tietoja kuin pelkällä kvantitatiivisella tutkimuksella voitaisiin saada. Kysely oli avoinna 15.11.–26.11.2021. Vastausprosentiksi saatiin 34,9 %. Etätyön merkittävimmiksi hyödyiksi havaittiin työ- ja vapaa-ajan joustavampi yhteensovittaminen ja se, että etätyössä keskittyminen on parempaa. Kommunikaation koetaan onnistuvan hyvin etätyössä, mutta kasvokkain tapahtuvaa kommunikaatiota pidetään myös tärkeänä. Esimerkiksi kehitys- ja ideointipalaverit olisi hyvä järjestää mahdollisuuksien mukaan kasvokkain. Lisäksi hiljaisen tiedon siirtyminen on vähäisempää etätyössä. Etätyö soveltuu hyvin tutkimus- ja tuotekehitystyöhön, eikä sen koeta heikentävän merkittävästi kykyä innovoida. Tulosten perusteella etätyötä haluttaisiin tehdä enemmän kuin 40 % työajasta ja etätyötä pidetään tehokkaana työskentelytapana. Kyselyssä ei selvitetty, minkälaisia etätyömääriä vastaajat ovat tehneet vahvan etätyösuosituksen aikana. Osa vastaajista on saattanut olla muita enemmän lähitöissä, mikä voi vaikuttaa tuloksiin. Saadut tulokset olivat kuitenkin samansuuntaisia kuin aikaisemmissa tutkimuksissa. Suurin osa tähän kyselyyn osallistuneista oli erittäin kokeneita ja työnsä hyvin osaavia työntekijöitä, mikä voi lisätä etätyömyönteisyyttä tuloksissa.
  • Saavalainen, Anu (2022)
    Medication related risks have been identified as one of the main threats to patient safety, both internationally and nationally. In Finland, implementation of pharmacotherapy in health services system is guided by the Safe pharmacotherapy -guideline. The guideline instructs work units to implement a pharmacotherapy plan, which is a statu-tory quality management document to describe the unit’s pharmacotherapy process and related responsibilities and obligations. However, there is currently limited research data available on pharmacotherapy plans and their impact on medication safety. The aim of this study was to explore the use of pharmacotherapy plans as a tool for promoting medication safety in the Finnish health services system with an emphasis on systems-based risk management. The research was con-ducted as an electronic survey in November-December 2021. The target group of the survey was health care professionals licensed as nurses and pharmacists who are working in wards or clinics or otherwise participate in drawing up or updating of pharmacotherapy plans. The study analyzed 901 responses. Most respondents (90 %) worked as licensed nurses and 10 % as pharmacists. The majority of the respondents’ units (91,5 %, n=824) had a pharmacotherapy plan. Medication safety practices were comprehensively described in pharmacotherapy plans and no significant differences observed between work environments. The multi-professional development processes of pharmacotherapy plans were not complete, only 11,6 % of the units the writing was done in multi-professional collaboration. Medication safety practices were best implemented in university hospitals (m. 3,87, sd. 0,57), with the difference being statistically significant for primary healthcare wards (m. 3,51, sd. 0,63, p<0,001) and social care housing services units (m. 3,63, sd, 0,68, p=0,018). The comprehensiveness of the content in pharmacotherapy plans and the implementation of medication safety practices were correlated (r=0,60, p<0,001). Pharmacotherapy plan is an important tool for systems-based medication safety promotion in the Finnish health services system. There is need for improvement in the multi-professional collaboration when developing the plans and in training the healthcare staff of practices described in the unit’s pharmacotherapy plans. In the future, special emphasis should be placed on the medication safety and development of primary healthcare wards and social care units.
  • Tapanila, Tiina (2022)
    Lääkkeiden saatavuushäiriöt ovat yleistyneet Suomessa ja muualla maailmassa aiheuttaen lisätyötä ja -kustannuksia lääkealan toimijoille. Saatavuushäiriöt voivat aiheuttaa katkoksia lääkehoitoon tai saatetaan joutua turvautumaan muihin hoitovaihtoehtoihin, mikä voi johtaa potilasturvallisuuden vaarantumiseen. Tämän tutkimuksen tavoitteena oli antaa yleiskuva saatavuushäiriöistä ja saatavuushäiriövalmisteiden ominaispiirteistä Suomessa keväällä 2020. Tutkittaviin ominaispiirteisiin kuuluivat mm. lääkkeen terapiaryhmä, myyntiluvan haltija, häiriön kesto, valmisteen hintaluokka, kuuluminen velvoitevarastoitavien valmisteiden tai Maailman terveysjärjestö WHO:n välttämättömien lääkkeiden luetteloon ja myyntiluvan myöntövuoteen perustuva lääkkeen elinkaarivaihe. Saatavuushäiriövalmisteiden (n=879) tiedot kerättiin myyntiluvan haltijoiden Lääkealan turvallisuus- ja kehittämiskeskus Fimealle kahden kuukauden aikana (14.2.–15.4.2020) toimittamista tai voimassa olevista saatavuushäiriöilmoituksista. Aineistoa täydennettiin hinta- ja korvattavuustiedoilla Kansaneläkelaitoksen lääketietokannasta sekä tiedoilla muista markkinoilla olevista pakkauskoista, vahvuuksista ja vaihtokelpoisista lääkevalmisteista. Aineistosta tehtiin kuvaileva tilastollinen analyysi käyttäen perustunnuslukuja ja -jakaumia. Analyysissä keskityttiin pääasiassa avohoidossa käytettäviin reseptivalmisteisiin (n=654). Ihmislääkkeiden saatavuushäiriöt (n=829) koskivat etenkin sairausvakuutuksesta korvattavia reseptivalmisteita (65 % kaikista saatavuushäiriöistä), ja ne keskittyivät suurten potilasryhmien käyttämiin lääkkeisiin, kuten sydän- ja verisuonisairauksien lääkkeisiin (31 %) ja hermostoon vaikuttaviin lääkeaineisiin (28 %). Avohoidon reseptivalmisteiden häiriöistä yli puolet (53 %) kohdistui rinnakkaisvalmisteisiin. Häiriövalmisteet kuuluivat elinkaarivaiheeltaan vanhempiin ja hintaluokaltaan edullisempiin valmisteisiin. Viidennes valmisteista (19 %) kuului velvoitevarastoitavien tai WHO:n välttämättömien lääkkeiden luetteloon. Rinnakkaisvalmiste löytyi 73 prosentille häiriövalmisteista. Vain kolme prosenttia myyntiluvan haltijoista oli tehnyt ilmoituksen saatavuushäiriöstä Fimealle vaadittua kahta kuukautta ennen myynnin keskeytymistä saatavuushäiriön vuoksi. Tulosten perusteella saatavuushäiriöt Suomessa koskevat samankaltaisia lääkevalmisteita kuin muuallakin maailmassa. Tämän osoitti myös tutkielman kirjallisuusosassa toteutettu kansainvälistä empiiristä saatavuushäiriötutkimusta koskenut systemaattinen kirjallisuushaku. Valtaosaan saatavuushäiriöistä on mahdollista reagoida apteekissa toimittamalla rinnakkaisvalmiste, kun taas osa vaatii yhteydenottoa lääkkeen määränneeseen lääkäriin. Saatavuushäiriötiedon linkittämistä sähköiseen reseptijärjestelmään ja lääkevaihdon laajentamista farmasian ammattilaisille voisi harkita toiminnan kehittämiseksi saatavuushäiriötilanteissa. Covid-19-pandemia on lisännyt kansainvälisiä toimia häiriötilanteiden hoitamiseksi. Tätä varten kehitetään yhteisiä toimintatapoja muun muassa Euroopan unionissa, jossa tavoitteena on luoda kaikki jäsenmaat kattava saatavuushäiriöportaali.
  • Saksa, Mari (2022)
    There are certain characteristics in children’s medication process, such as weight or body surface area-based drug dosing and off-label use of medications, that expose children to medication errors. Small children especially are prone to physical injuries resulting from medication errors. High-alert medications bear a heightened risk of causing significant, even life-threatening harm to a patient when used in error. The aim of this study was to promote children's medication safety by identifying medication errors and contributing factors to errors associated with the use of high-alert medications in pediatric medication process in a hospital environment. The data of this retrospective register study consisted of voluntary medication error reports (HaiPro) made in the pediatric and adolescent units at Helsinki university hospital (HUS). ISMP's (Institute for Safe Medication Practices) list of high-alert medications in acute care settings was used to limit the data. The data was analyzed by using both quantitative and qualitative methods. The aim of the quantitative analysis was to report the frequencies (n) and proportions (%) of high-alert medications and routes of administration and the aim of the qualitative analysis was to identify the types of medication errors and contributing factors in the data. ISMP’s high-alert medications accounted for approximately one-fifth (19.7%) of all medication error reports made in pediatric and adolescent units in 2018–2020. Twelve medications and intravenous route covered approximately 65.0% of all high-alert medications and routes of administration mentioned in the data. Medication errors were mostly identified in medication administration stage (43.3%) and administration errors were often preceded by prescribing errors. Dosing errors (20.5%) and documenting errors (16.8%) were the most common medication error types in the data. Errors associated with dosing and infusion rate were most often involved in severe medication errors. The most frequently identified contributing factors in the data were associated with the work situation and conditions, documenting and information transfer or medications. More detailed risk analysis considering high-alert medications and the intravenous medication process and targeting preventive barriers to identified risk areas are recommended in pediatric and adolescent units in the future. Barriers should be planned to cover the entire medication process. Among different types of medication errors, multiple dosing errors and errors during the programming of infusion rate require special attention in the future.
  • Lahti, Aapeli (2022)
    Lääkeaineiden niukkaliukoisuus on yhä enemmän esiintyvä ongelma lääketeollisuudessa. Erityisesti BCS ryhmän II lääkeaineet ovat potentiaalisia liukoisuusominaisuuksia parantaville menetelmille. Tässä työssä näistä menetelmistä keskitytään nanokiteen, ko-kiteen ja ko-amorfisen systeemin muodostukseen ja lääkeaineena käytetään inodmetasiinia (BCS ryhmä II). Kyseisillä menetelmillä on onnistuttu parantamaan indometasiinin liukoisuusominaisuuksia, mutta vertailevia tutkimuksia ei ole aiemmin tehty. Nanokide valmistettiin märkäjauhamalla käyttäen poloksameeri 188 -stabilisaattoria. Ko-kiteen valmistuksessa käytettiin liuottimen haihdutus -menetelmää ja ko-muodostajana sakariinia. Ko-amorfisten systeemien ko-muodostajina käytettiin l-tryptofaania ja sitruunahappoa ja valmistus toteutettiin kuulamyllyllä jauhamalla. Karakterisointimenetelmillä (DLS, DSC ja XRPD) oli mahdollista todentaa nanokiteillä ja ko-kiteillä halutut ominaisuudet (partikkelikoko ja kiderakenne). Ko-amorfinen systeemi ei työssä käytetyllä menetelmällä saavuttanut amorfista rakennetta kummallakaan ko-muodostajalla. Vaikka jauhe osittain muuttui kellertäväksi (viitaten amorfiseen indometasiiniin) olivat XRPD:n ja DSC:n tulokset kiteiselle aineelle tyypillisiä. Nanokiteellä ja ko-kiteellä saavutettiin puhdasta indometasiinia parempi ominaisliukenemisnopeus sekä liukenemisnopeus jauheesta lapamenetelmällä. Systeemien välisessä vertailussa huomattiin, että nanokiteellä oli parempi liukenemisnopeus molemmissa kokeissa. Ero on selkeämmin nähtävissä lapamenetelmässä: pieni partikkelikoko mahdollistaa suuren suhteellisen pinta-alan liukenemista varten. Systeemien fysikaalista stabiilisuutta tutkittiin yhdeksän kuukauden ajan suljetussa muoviastiassa laboratorio-olosuhteissa (huoneenlämpö ja normaali ilmankosteus). Kummassakaan systeemissä ei ollut nähtävissä kiderakenteen muutoksia. Nanokiteillä oli havaittavissa lievää partikkelikoon kasvua, mikä on selitettävissä ennen koetta tehdyn sekoituksen tehottomuudella
  • Lindstedt, Hanna (2022)
    Drug-induced liver injury (DILI) is a relatively rare hepatic condition that can be classified as predictable and unpredictable. However, DILI is a primary reason for drug withdrawals, post-marketing warnings, and restrictions of use. DILI is a problem for the drug users but also for the pharmaceutical industry and regulatory bodies. From the perspective of patients' and clinicians', DILI is the major cause of acute liver injury. At present, a major problem predicting DILI in drug discovery is a poor understanding of its mechanisms as well as the complexity of DILI pathogenicity. The main mechanism behind DILI are alterations in bile acid homeostasis, oxidative stress, and mitochondrial dysfunction. More than 50 % of drugs causing DILI are causing mitochondrial impairment. If the normal function of mitochondria is disturbed, the energy production of the cell decreases, and cell function decline leading eventually to the cell death. In this study prediction of mitochondrial toxicity was studied using cryopreserved primary hepatocytes of humans and rats. The aim of the study was to clarify if there are interspecies differences in the prediction of toxicity but also investigate possible differences in the mechanisms behind hepatotoxicity by using three well-known compounds toxic to mitochondria. To determine these differences, total cellular ATP was measured after 2- and 24- hour exposure time to gain information on overall viability and possible adaptive responses. Mitochondrial energy pathways were studied as a real-time monitoring acute exposure of test compounds. Morphology, location, and possible adaptive response of mitochondria were studied using a fluorescent probe and antibody staining combined with high content imaging (HCI). Overall, primary rat hepatocytes were more sensitive to the test compounds than human hepatocytes. Also, there were differences between human hepatocyte batches that may reflect the metabolic differences between hepatocyte donors. Immunolabeling did not bring any additional values compared to the fluorescent probe staining in the study of morphology of mitochondria. Additionally, it was noticed that treatment with paraformaldehyde significantly changed the hepatocyte mitochondria morphology. Overall, more effort is needed to develop image analysis of mitochondria morphology. Finally, studying mitochondrial morphology has proven to be difficult, and this study did not unfortunately reveal any information about the adaptive responses of mitochondria for drug-induced liver injury.
  • Monola, Julia (2022)
    Native nanofibrillated cellulose is wood-derived, animal-free biocompatible biomaterial which has proved the suitability of nanoscale cellulose fiber based hydrogels for 3D cell culturing and wound healing applications. The problem of freeze-drying nanofibrillated cellulose hydrogel (NFCh) has been the aggregation of the hydrophilic fibrils of the NFC during freeze-drying, which leads deformed freeze-dried cake and unsuccessful reconstitution of the sample. Molecular Dynamic (MD) simulations have been earlier applied in formulation design of NFCh for freeze-drying successfully by screening excipients based on their attraction to the surface of NFCh. The weakness of MD simulations is it can only model the fresh formulation system intend to freeze-dry, but not the actual freeze-drying process and the effect of it and the excipients to the material. To evaluate the protecting properties of excipients and therefore the accuracy of the MD simulations detailed information about changes in the physical state and molecular orientation of the formulation before and after freeze-drying is needed. Non-invasive and label-free Raman spectroscopy can be used to determine vibrational modes of molecules to investigate changes in molecular orientation of the material. The aim of this study was to investigate the possible molecular changes induced by freeze-drying of NFCh-based formulations utilizing Raman spectroscopy and evaluate the connection of the results to MD simulations. NFCh with different excipients was freeze-dried and physicochemical properties, rheology and Raman signal were measured before and after freeze-drying and compared to the literature of MD simulations. The principal component analysis (PCA) was done to the Raman spectra and differences evaluated. The spectra of all formulations differed before and after freeze-drying, and more detailed analysis was done to two most potential 0.8% NFCh based formulations, lactose 300 mM and lactose 250 mM + glycine 50 mM. They had great attraction to NFCh in MD simulations and very similar rheological properties before and after freeze-drying and reconstitution. The spectra of different state of both formulations different on areas between 400 - 500 cm-1 and 850 - 900 cm-1 based on PCA analysis contributing the mutarotation of lactose during freeze-drying and reconstitution. Freeze-drying and the absence of water molecules in NFCh formulation favor different ratios of β and α anomers than the fresh hydrated state which could be detected utilizing Raman spectroscopy. Therefore, Raman spectroscopy was confirmed to be a sensitive option to assess subtle changes in molecular orientation in fresh, freeze-dried, and reconstituted NFCh-based formulations, resulting in a detail knowledge of the molecular behavior of excipients which could be applied in MD simulations and design of better freeze-drying formulations in future.
  • Pihlajakoski, Marjo (2022)
    Operations of pharmaceutical supply chain and medication management practices will be evaluated as part of the ongoing social and health services reform in Finland. One of the goals is to develop digital medication management tools and services to meet the needs of both healthcare professionals and medicine users. The aim of this study was to examine population's willingness to use on new digital services by community pharmacies to promote rational pharmacotherapy and to support cooperation between those involved in the medication use process. The material for this study consisted of the national population survey conducted in 2020 for the VN TEAS report “Activation of price competition for pharmaceutical products and the population's expectations for pharmacy operations” (online survey for 18–79-year-old adults, n = 1650). The survey respondents represented well the target population expect those with higher educational level were over-represented. The current study focused on questions related to digital medication management services provided by community pharmacies, which were divided into the following 4 topics to form sum variables: 1) purchasing and dispensing process of medicines (4 items), 2) customer`s communication with pharmacy and health care personnel (2 items), 3) pharmacy and healthcare personnel`s communication with the customer (4 items) and 4) support services for medication self-management (12 items). The associations of the background variables to the sum variables were calculated using cross-tabulation and the Chi-Square test. Frequencies and percentages were used to present. The majority (85–90%) of the respondents were in favor of the possibility of sending messages electronically between the customer, the community pharmacy and other healthcare personnel by using a shared communication channel, such as My Kanta to update medication information online. Multimorbidity, medication use, and higher medication costs increased the respondent’s positive attitude towards the electronic communication channel. Three-quarters (76%) of respondents were willing to use electronic medicine purchasing and dispensing services. Younger respondents (18–34 years) were more interested in these services than older ones. The electronic medication self-management support services had more discrete opinions among respondents. More than half of the respondents indicated their strong willingness to use at least one of the medication self-management support online services listed in the survey instrument. Those aged 18–34 years (69%), those with higher education (62%), those living in the Province of Southern Finland (60%) and those living in the Helsinki Metropolitan Area (67%) were more positive than others. Of the respondents who opted for pharmacy's remote online services, 55% were willing to seek advice for reconciling their medication list. According to the survey, Finnish adults are willing to use new electronic services by community pharmacies. In particular, they were willing to use a shared electronic communication channel between the customer, the pharmacy and other healthcare personnel, such as MyKanta to update information related to their medication. The willingness to have support self-care support for medication self-management primarily from the pharmacy's online services was lower than the willingness to use online purchasing and dispensing services. Of the remote medication self-management services medication reconciliation had the highest demand. Future research should focus on enhancing use of electronic medication self-management services provided by community pharmacies. Further research should also be targeted to understand medicine user needs for support as it may vary between patient groups, requiring segmentation of services.
  • Haapalainen, Joonatan (2022)
    Traditional 2D cell cultivating vessels and experimental models cannot often simulate natural chemical and physical environment of different cell types. For example, availability of oxygen, chemical gradients, messaging molecules, fluid pressure, flow and surface topography are factors that may affect significantly in cell differentiation, growth, cellular structure, and metabolism. Modular bioreactors like Quasi-Vivo® -system can be used to simulate these factors. Liposomes are particles of phospholipid bilayer with aqueous space enclosed within. They can be modified in numerous ways, like loading them with hydrophobic and hydrophilic molecules, changing their transition temperature or coating them according to different needs. Doxorubicin is effective and widely used cytostatic agent, but when administered as a free drug it has often severe side-effects, like cardiotoxicity. Goal of this thesis is to determine appropriate manufacturing parameters and verify adequate shelf-life of ICG-Doxorubicin liposomes, that they are applicable for future in vitro experiments. Then survival of HepG2 cell line under flow in Quasi-Vivo®-equipment is determined, after which A549 and HepG2 will be then combined into one two-cell model. Finally, a simple illumination experiment in this cell model with previously made liposomes is conducted, and the effect in whole system is examined. Using protocol presented in this thesis it is possible to produce successfully and repeatedly liposomes with both ICG and doxorubicin encapsulation over 70%. Their shelf-life was at least 14 days when stored in 4°C protected from light. This was determined to be sufficient for in vitro testing. Cultivating A549 and HepG2 cell lines combined in the same system with shared media and fluid flow conditions was successful. Neither of the cell lines show significant difference in viability when compared to static control. When light-activating liposomes are administered to the system and then illuminated, from preliminary results we can see significant difference in drug effect. Both illuminated chambers and off-target chambers connected via Quasi-Vivo® show increased suppression, which shows promise that this in vitro model would be useful for future experiments.
  • Repo, Amanda (2022)
    The use of different methods of extended reality (xR) as a support in teaching has been under research for a long time. Although the use of various xR-technologies in other fields of healthcare, such as medical and nursing education, is already common, their use in pharmacy education is not yet well established. There is evidence that xR-technology has a positive impact for example on students’ motivation and learning outcomes. On the other hand, there are limiting factors that inhibit the technology becoming widespread, such as costs as well as a lack of knowledge about the technology usability. The aim of the study was to investigate usability and advantages of the augmented reality (AR) in a laboratory course as an educational supportive tool by using AR-glasses. The aim was also to investigate the learning outcomes of the students who participated in the study in three different phases: before carrying out the laboratory work (pre), immediately after the laboratory work (post) and in the course exam (delayed). Furthermore, the motivation of the students to use new technology in their studies was studied. The research was done in a collaboration with the Centre for University Teaching and Learning (HYPE) and with Sciar Company Oy. The researchers of HYPE were responsible for the pedagogical point of view, whilst the experts from the Faculty of Pharmacy were responsible for the study measurements of laboratory work related content knowledge. The research was implemented in two laboratory courses in Bachelor of Science level pharmacy studies: Medicinal product II and Pharmaceutical biology and asepsis in the fall of 2020. The students (n=18) prepared eye drops by using AR-glasses in the Medicinal product II -course and reference group (n=14) without AR-glasses. In the course of Pharmaceutical biology and asepsis, students (n=7) used AR-glasses to study the microbiological purity of the eye drops by utilizing membrane filtration method in cleanroom and reference group (n=9) without AR-glasses. ln addition, a serial dilution method was performed on a 96-well plate using an AR mobile application. The effect on learning outcomes was evaluated by using six open-ended questions measuring the understanding of content knowledge underlying the laboratory work, that were answered by the students at three different stages of the study (pre, post, delayed). To measure the usability of the AR equipment, a five-point Likert scale questionnaire studied the experimental groups students’ opinions on whether the AR mobile application could provide sufficient guidance and feedback while performing the laboratory work. In an open question, the students had the possibility to comment on the overall user experience of the AR mobile application. There were no statistically significant differences in learning outcomes between the AR-group and the reference group in both laboratory courses. The results showed indicative differences in short-term and long-term learning, with the AR-group achieving better learning outcomes in the short-term and the reference group in the long-term. In the course of Pharmaceutical biology and asepsis, the learning outcomes were the opposite. Students’ were found to be receptivity to the new technology that together with motivation supports positively the learning process. The use of AR-hardware increased certainty and reduced nervousness about the use of AR technology. As a conclusion, the study could not demonstrate the benefit of AR-technology in student learning outcomes. The study was limited by the small sample size. However, further studies are encouraged due to students’ positive attitudes and motivation towards AR technology. Regarding further studies, it is important to take into consideration the different backgrounds and learning methods of students. Thereby, the effects of xR-technologies on learning outcomes can be assessed as objectively as possible.
  • Heininen, Susanna (2022)
    The medication-use process in hospitals includes several risks which can lead to medication errors. Medication errors can be prevented and managed by adding automation and technology solutions to the medication-use process, such as clinical decision support system (CDSS) integrated into electronic medication administration record (eMAR), unit dose drug distribution system (UDDDS), automated dispensing cabinet (ADC) and bar-code medication administration (BCMA). A closed loop medication management process can be created by integrating different methods and technologies seamlessly. It improves medication safety by decreasing human errors and allows the access to the patient’s medication information in real time. The closed loop medication management process is not yet fully in use in any Finnish hospital, but parts of it have already been implemented. Helsinki University Hospital (HUS) wants to improve the closed loop medication management process by piloting the use of unit dose (UD) bags in the medication- use process and to study its effects on medication safety. The aim of the study was to determine the incidence of the medication dispensing errors and procedural errors, the working time of the nurses, and the nurses' opinions on the current drug dispensing model in a hospital ward before the introduction of the unit dose drug distribution system. The study was conducted as a mixed-method study, which utilized an observational method and an online survey. The data were collected at HUS internal medicine inpatient ward by observing the dispensing of morning medicines for ten days and through an electronic survey sent to the ward’s nurses. The overall incidence of dispensing errors in the current drug dispensing process was 40,1 % (553/1379). Of these, 3,2 % (44/1379) were medication dispensing errors, and after the excluding prescribing errors (n=22), the incidence was 1,6 %. These prescription errors were mainly related to prescribing medications outside the hospital's formulary. In addition, the incidence of procedural errors was 37 % (509/1379). Of the procedural errors, 57 % (292/509) were related to the unattached or missing barcodes and 37 % (186/509) to hygiene deficiencies in drug dispensing. On average, nurses spent 4,5 minutes per patient on medication dispensing and patients had 7 morning medications. The results of the survey also revealed problems related to barcodes as well as hygiene deficiencies, which supported the results of the observations. Significant safety risks, such as unattached barcodes, missing barcodes, and deficiencies in hygiene were identified in the current drug dispensing process. The study indicates that system-based risk management approach is not yet fully understood in hospital units. The root cause of procedural errors should be investigated more and review the ward's instructions with staff, to reduce their incidence in the future. At the end of 2021 a unit dose drug distribution model will be piloted in the ward, which may be one possible way to reduce errors related barcodes and hygiene. In addition, to improve the medication safety, physicians should order medications from hospital's formulary, so that generic substitution would no longer need to be made at the distribution stage. It would be useful to include a category of incorrect orders in the future research setups that investigate medication errors in the dispensing phase to identify such potential risk situations.
  • Ollinkangas, Joni (2022)
    The problems caused by hypromellose in sterile filtration of ophthalmic products in the pharmaceutical industry were investigated. The research project was performed at NextPharma Oy's ophthalmics manufacturing facility in Tampere during the autumn of 2020. Hypromellose is an excipient commonly used in ophthalmic products as a viscosity enhancer to prolong the contact time of the preparation on the eye surface. In the ophthalmics compounding process, hypromellose is first dispersed by slowly sprinkling it into a hot solution and thoroughly mixing, after which the solution is cooled to room temperature. During cooling, the hypromellose dissolves and gels, increasing the viscosity of the solution. Incomplete dispersion or dissolution of hypromellose during the manufacturing process can slow down the filtration rate or even clog the filter completely due to undissolved hypromellose polymer material. Hypromellose is an industrially produced cellulose derivative that often contains some amounts of unreacted cellulose and other sparingly soluble polymer particles as impurities, which can also cause problems in filtration processes. Sterile filtration is a commonly used sterilization method for ophthalmic products, in which the prepared bulk solution is filtered through a 0.1 to 0.2 µm pore size filter membrane into a sterile receiving vessel. Due to the very small pore size, sterile filters are easily clogged if the solution contains poorly dissolved material. The purpose of this work was to collect additional information on the possible causes of clogging caused by hypromellose and to determine whether the filterability of a solution containing hypromellose can be improved by optimizing the manufacturing process parameters. The design of experiments was prepared, creating a two-level full-factorial test matrix without replicates and with three centre points. Four different process parameters were used (mixing time, mixing speed, dispersion temperature, and cooling temperature). Minimum and maximum levels for the parameters were obtained in the initial tests, after which the test solutions were prepared and filtered in a randomized order according to the test matrix. The aim of the screening was to find out which parameters were affecting the filterability and what would be their optimal combination that would maximize the filtration rate and the yield of filtration. Finally, the optimized parameters were used to test different batches of hypromellose, comparing the results to previous filtration tests. Additionally, an alternative hypromellose dispersion method was tested to minimize the amount of insoluble material remained during the dispersion and cooling steps. Of the parameters tested, mixing speed was the least significant, while cooling temperature had the most effect on the filtration results. The solutions with lower cooling temperature had better filtration results, which may be due to reduced aggregation of hypromellose due to increased hydration of the polymer chains. The temperature behaviour of hypromellose solutions could be an interesting subject for further investigation. Longer mixing times and higher dispersion temperatures produced slightly better filtration results on average, but the differences were not statistically significant. Most challenging in the study was controlling the temperature and mixing of the solutions, and the retention of insoluble hypromellose material at the walls of the compounding vessel. The alternative dispersion method gave promising preliminary results, but the method still requires further testing. It would be important to also find the root cause of the filter clogging mechanism e.g., by further analysing the clogged filter membrane. The study provided additional useful information of the behaviour of hypromellose solutions in solution preparations and during sterile filtration, which has been helpful in solving production problems.
  • Aromaa, Virve (2022)
    Mild traumatic brain injury (mTBI) is an insult to the brain caused by an external force. Typically contact sport players and military soldiers are prone to mTBI. TBI events trigger pathological processes in the brain and may cause long-term and progressive damages. Increased formation and accumulation of misfolded toxic protein aggregates in the brain leading to neuronal death has been observed after mTBI. In particular, repetitive mTBIs are a risk factor for the development of many neurodegenerative diseases, such as chronic traumatic encephalopathy, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. As there is no curative treatment to neurodegenerative diseases, research regarding neurodegenerative processes is highly important. Prolyl oligopeptidase (PREP) negatively regulates functions of protein phosphatase 2A (PP2A). It has been shown that PP2A activity is decreased in the brain of those with neurodegenerative diseases and TBI patients, which is thought to be a contributing factor to the development of pathologies of neurodegenerative diseases. The primary objective of this study was to study behavioural changes after repeated mild TBI in PREP knockout mice. The aim was to model mild repeated brain injuries that are common, for instance, in contact sports and that are not accompanied by skull fractures or brain swelling. The intension was to clarify the involvement of the PREP enzyme in behavioural changes induced by repeated mTBI’s and to elucidate long-term pathological changes in the brain. The injury was induced as a closed-head injury with an electromagnetic impactor with one hit every 24 hours and altogether 5 times. A locomotor activity test was performed before the induction of brain injury and was repeated 3 times after mTBI induction. Barnes maze test was used to assess memory and learning functions. In this thesis the brain samples from a previous study were included to also determine the accumulation of total tau protein in wild-type mice. The wild- type mice were administered with either the PREP inhibitor KYP-2047 or HUP-46 10 mg/kg (i.p.) immediately after each hit. After euthanasia, the Western blot assay and immunostaining were performed to study the amount of phosphorylated tau, neuroinflammation, activity of PP2A and autophagy. No differences were found between the sham group and TBI group on the locomotor activity and Barnes maze tests in PREP knockout mice. There was no consistency in total tau protein in wild-type mice treated with PREP inhibitors. In PREP knockout mice there was an upward trend in PP2A levels after mTBI. Repeated mTBI increased markers of phosphorylated tau and neuroinflammation significantly. No significant difference was observed in autophagic function. The results of this thesis are indicative. Due to the low number of animals, the results need to be confirmed in subsequent studies with greater amounts of animals. Based on the results, it seems that absence of the PREP enzyme protects from memory impairments after repeated mTBI. Increased tau protein phosphorylation and neuroinflammation were observed in the TBI group which indicate that PREP alone is not responsible for the development of pathological changes.
  • Mäkinen, Heljä (2022)
    Municipal case management is an activity that assesses various functional capacity indicators, utilizing the elderly’s state of health and coping in everyday life. The goal of case management is to refer clients to suitable services, such as home care or a doctor's visit. The problems related to drug treatments are only superficially reviewed. The involvement of a pharmacist in the assessment of case management would provide an opportunity to address the problems of pharmacotherapy and to provide adequate support for the implementation of pharmacotherapy. In this thesis, a remote service of a pharmacist was piloted for new clients over the age of 65 living at home as part of case management. Pharmacist reviewed medications remotely using medication risk management checklist LOTTA. The study examined the suitability of the LOTTA for medication reviews and the problems associated with medications of the elderly participating in case management. In addition, the suitability of pharmacovigilance assessments as a remote service as part of a comprehensive assessment of functional capacity and coping with everyday life was examined. The research material was collected at the case management unit of the city of Turku. The study involved 50 volunteer Finnish-speaking customers over the age of 65, for whom were assessed for a case management at Turku's case management unit. In addition to the assessment of normal case management, two pharmacists with comprehensive medication review qualifications reviewed medications using the medication risk management checklist LOTTA. Subjects were interviewed by telephone. If the pharmacist estimates that the subject will benefit from a multi-professional comprehensive medication review, the physician and pharmacist collaborated to conduct a review using a videophone application. Subjects background information, responses, observations made by pharmacists, and actions taken by physicians were recorded on an electronic form and analyzed. The mean age of the study participants (n = 50) was 82 years (range 67–98). Of these, 36 were women (72%) and 14 were men (28%). Most subjects were multidrug-treated (average medication 10.3, range 3–28). Each subject had at least one drug can be used with consideration for use in the elderly, as defined in the Fimea Drug 75 + database (Class C). 30% of subjects did not have a medication list and 34% reported lack of regular medication monitoring. 96% of the subjects had experienced a symptom on the LOTTA list that repeatedly interferes with their lives. The most common of these were problems such as constipation (54%). Pharmacists proposed changes for medication for 96 % of subjects. The most common proposed change was a change in the time of dosing (46%). Pharmacists estimated that 14 (28%) subjects would benefit from a multi-professional comprehensive medication review. In these cases, pharmacists made an average of 8.1 proposed changes for the physician, and the physician made an average of 6.9 changes for each subject. The most common challenges in coping with medication were symptom, which may be due to adverse drug reactions, a lack of follow-up to medication, and the absence of a treating physician. The results suggest that medication should be reviewed during the case management. The LOTTA list made it possible to identify and address the pharmacological problems of the elderly. The participation of a pharmacist in the assessment of the need for a multi-professional service remotely was possible, but it must be further developed. More research is needed on the benefits of multi-professional case management with a larger sample size.