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The objective of this study is to describe and analyze adverse drug events (ADE) identified using the Global trigger tool (GTT) in a Finnish tertiary hospital during a 5-year period and also to evaluate whether the medication module of the GTT is a useful tool for ADE detection and management or if modification of the medication module is needed. A cross-sectional study of retrospective record review in a 450-bed tertiary hospital in Finland. Ten randomly selected patients from electronic medical records were reviewed bimonthly from 2017 to 2021. The GTT team reviewed a total of 834 records with modified GTT method, which includes the evaluation of possible polypharmacy, National Early Warning Score (NEWS), highest nursing intensity raw score (NI), and pain triggers. The data set contained 366 records with triggers in medication module and 601 records with the polypharmacy trigger that were analyzed in this study. With the GTT, a total of 53 ADEs were detected in the 834 medical records, which corresponds to 13 ADEs/1000 patient-days and 6% of the patients. Altogether, 44% of the patients had at least one trigger found with the GTT medication module. As the number of medication module triggers increased per patient, it was more likely that the patient had also experienced an ADE. The number of triggers found with the GTT medication module in patients’ records seems to correlate with the risk of ADEs. Modification of the GTT could provide even more reliable data for ADE prevention.

Background and objectives: Wrong fluid product selection may cause harm to patients. This study aimed to describe voluntarily reported wrong fluid product selection incidents, including their consequences, the reported latent conditions and active failures leading to these and the suggested safeguards to prevent their occurrence, and to compare the suggested and literature-based safeguards to improve the fluid therapy safety within the intensive care (ICU) environment. Methods: All voluntarily and anonymously reported wrong fluid product selection incidents in all Finnish ICUs during 2007–2017 were reviewed. The incident reports included categorized data that were analyzed quantitatively, and narratives that were analyzed qualitatively, using content analysis. The results were reported as frequencies and percentages and described by using Reason's model of human error. Results: Over the eleven years, one wrong fluid product selection incident was reported every six days (n=663; 584 errors, 79 near misses); most were reported to have occurred during the dispensing/preparing phase (92%). Of the 584 reported selection errors, a quarter (26%) was reported to have caused consequences to patients, and one third (35%) to have required corrective or monitoring actions. The main reported latent conditions to the incidents were Working environment and resources (e.g. workload and time pressure) (29%), Similar-looking and -sounding names or shared features of the product containers (i.e. the LASA phenomenon) (28%) and Working methods (22%); and the main reported active failures were a lack of concentration, or forgetfulness (26%). Some usable suggestions of safeguards were made, e.g. optimizing fluid storage (15%) or utilizing checking practices (21%). While requiring accuracy, i.e. reminding staff of diligence and to be more attentive to detail during the whole medication process, was emphasized in most reports (71%), involving manufacturers in redesigning labels of fluid products, utilizing technology and strengthening pharmacy services are advocated existing literature. Conclusions: Wrong fluid product selection incidents with various latent conditions and active failures were reported more than once a week. To minimize the serious LASA phenomenon,multi-professional collaboration, coordinated international discussion and agreements of solutions with manufacturers, regulators and end-users, are needed. However, work is also needed to reduce the other latent factors, such as Working environment and resources as well as cognitive biases in daily work that may contribute to the occurrence of LASA related errors.

Background Fluid therapy is a common intervention in critically ill patients. Fluid therapy errors may cause harm to patients. Thus, understanding of reported fluid therapy incidents is required in order to learn from them and develop protective measures, including utilizing expertise of pharmacists and technology to improve patient safety at the national level. Objectives To describe fluid therapy incidents voluntarily reported in intensive care and high dependency units (ICUs) to a national incident reporting system, by investigating the error types, fluid products, consequences to patients and actions taken to alleviate them, and to identify at which phase of the medication process the incidents had occurred and had been detected. Methods Medication related voluntarily reported incident (n = 7623) reports were obtained from all ICUs in 2007–2017. Incidents concerning fluid therapy (n = 2201) were selected. The retrospective analysis utilized categorized data and narrative descriptions of the incidents. The results were expressed as frequencies and percentages. Results Most voluntarily reported incidents had occurred during the dispensing/preparing phase (n = 1306, 59%) of the medication process: a point of risk. Most incidents (n = 1975, 90%) had reached the patient and passed through many phases in the medication process and nursing shift change checks before detection. One third of the errors (n = 596, 30%) were reported to have caused consequences to patients. One quarter (n = 492, 25%) of the errors were reported to have required an additional procedure to alleviate or monitor the consequences. Conclusions Utilizing national incident report data enabled identifying systemic points of risk in the medication process and learning to improve patient safety. To prevent similar incidents, initial interventions should focus on the dispensing/preparing phase before implementing active medication identification procedures at each phase of the medication process and nursing shift changes. Strengthening clinical pharmacy services, utilizing technology, coordinated by IV Fluid Coordinators and Medication Safety Officers, could improve patient safety in the ICUs.

The aim of this study was to describe identified risk areas related to the medication administration process in acute care in order to develop a three-dimensional-game intervention. A secondary analysis was conducted using (1) observed medication administrations (n = 1058) and identified medication errors in 2012 (n = 235), (2) a systematic review including a meta-analysis of previous medication administration educational interventions (n = 14) from 2000 to 2015, (3) incident reports of medication administration errors (n = 1012) from 2013 to 2014, and (4) focus group interviews with RNs' (n = 20) views in 2015. A qualitative content analysis was used to identify risk areas, and the data were organized according to the following main themes: (1) factors related to patients (patient identification, patients' characteristics or symptoms, and patients' allergies and interactions); (2) factors related to medications (medication information, changes in medications, generic substitutes, new drugs, look-alike/sound-alike drugs, demanding drug treatments, medication preparation, and administration techniques); (3) factors related to staffing (workload, skills, interruptions and distractions, division of work, responsibility, attitudes, and guidelines); and (4) factors related to communication (flow of information, communication with the patients, and marking of medication information). Identified risk areas could be used to develop interventions with the aim of increasing the safety of medication administration and nurses' skills.

Aims and objectives To describe ways of preventing medication administration errors based on reporters' views expressed in medication administration incident reports. Background Medication administration errors are very common, and nurses play important roles in committing and in preventing such errors. Thus far, incident reporters’ perceptions of how to prevent medication administration errors have rarely been analysed. Design and Methods This is a qualitative, descriptive study using an inductive content analysis of the incident reports related to medication administration errors (n = 1012). These free-text descriptions include reporters’ views on preventing the reoccurrence of medication administration errors. The data were collected from two hospitals in Finland and pertain to incidents that were reported between 1 January 2013 and 31 December 2014. Results Reporters’ views on preventing medication administration errors were divided into three main categories related to individuals (health professionals), teams and organisations. The following categories related to individuals in preventing medication administration errors were identified: (1) accuracy and preciseness; (2) verification; and (3) following the guidelines, responsibility and attitude towards work. The team categories were as follows: (1) distribution of work; (2) flow of information and cooperation; and (3) documenting and marking the drug information. The categories related to organisation were as follows: (1) work environment; (2) resources; (3) training; (4) guidelines; and (5) development of the work. Conclusions Health professionals should administer medication with a high moral awareness and an attempt to concentrate on the task. Nonetheless, the system should support health professionals by providing a reasonable work environment and encouraging collaboration among the providers to facilitate the safe administration of medication. Relevance to clinical practice Although there are numerous approaches to supporting medication safety, approaches that support the ability of individual health professionals to manage daily medications should be prioritised.

Aims The aim of this review was to identify methods for measuring Registered Nurses' medication administration skills and to describe these skills. Design A systematic literature review. Data sources The CINAHL, PubMed, Scopus, Cochrane, PsycInfo and Medic databases were searched for articles from the period 2007-2018. Review methods Two researchers independently selected the articles and evaluated their quality using the National Heart, Lung and Blood Institute study quality assessment tools. The data were analysed using content analysis. Results A total of 727 studies were identified of which 22 studies were included in this review. A total of six different measurement methods were identified: questionnaire or survey, observation, knowledge test or exam, focus group interviews, chart reviews and voluntarily reported errors. Different methods provided different information on medication administration skills. Medication administration skills were classified under nine areas: (1) safe ordering, handling, storing and discarding of medications, (2) preparing of medications, (3) the administration of medications to patients, (4) documentation, (5) evaluation and assessment of medication-related issues, (6) drug calculation skills, (7) cooperation with other professionals and (8) with the patients and (9) reporting of medication information. The results demonstrated that there are many areas that need to be improved to increase medication safety. Conclusions Medication administration includes many different phases, as a result of which nurses need to have many various skills to cope with medication administration as required by their profession. This review shows that nurses' medication administration skills need to be developed, and special attention should be paid to the preparation and administration phases. It is important to regularly utilise different teaching strategies and verify nurses' medication competence. As each research method has different limitations, it is vital that further studies combine different methods to form a comprehensive picture of nurses' medication administration skills.

Aim The aims of this qualitative descriptive study were to 1) explore and define radiographers' competence in intravenous pharmacotherapy before and after a simulation-based education, 2) examine radiographer's perceptions of transfer of learning into clinical practice. Method Sixteen diagnostic radiographers in one hospitals' Clinical Radiology Unit were individually interviewed before a multidisciplinary simulation-based pharmacotherapy education intervention in 2012 and fourteen were re-interviewed after the intervention 6–7 months later. Data were analyzed using qualitative content analysis. Results Before education the participants reported uncertain competence in pain management during imaging procedures and acute situations. These weak competence areas identified were strengthened and self-confidence grew. The intervention improved the domains of pharmacotherapy-related patient safety; teamwork development and communication skills. In addition, the radiographers indicated that the iv. pharmacotherapy knowledge from simulation learning was transferred to routine work. Conclusion The results of this study suggest simulation-based education is suitable for radiographers' pharmacotherapy learning. Adequate pain measurement and management are essential during invasive procedures and these skills can be realistically learned in simulations and transferred to clinical practice.

Reconstituting antibiotics for clinical use requires static postures and repetitive motions which may contribute to the development of musculoskeletal symptoms. Exposure to drugs can cause allergic contact reactions, with antibiotics being the most common cause for occupational contact sensitization among health care workers. We evaluated ergonomics and skin and respiratory tract reactions associated with parenteral antibiotic reconstitution among nurses and ward pharmacists in a tertiary hospital in Kuopio, Finland. A total of 28 ward pharmacists and 296 nurses were sent a link to a questionnaire asking about musculoskeletal symptoms and skin and respiratory tract reactions associated with antibiotic reconstitution. All of the 28 pharmacists and 92 nurses (response rate 100 and 31 %, respectively) answered the questionnaire. Musculoskeletal symptoms associated with antibiotic reconstitution were more commonly experienced by the pharmacists than by the nurses (68 vs. 5 %; p

The aim of this paper is to analyse how medication incidents are detected in different phases of the medication process. The study design is a retrospective register study. The material was collected from one university hospital's web-based incident reporting database in Finland. In 2010, 1617 incident reports were made, 671 of those were medication incidents and analysed in this study. Statistical methods were used to analyse the material. Results were reported using frequencies and percentages. Twenty-one percent of all medication incidents were detected during documenting or reading the documents. One-sixth of medication incidents were detected during medicating the patients, and approximately one-tenth were detected during verifying of the medicines. It is important to learn how to break the chain of medication errors as early as possible. Findings showed that for nurses, the ability to concentrate on documenting and medicating the patient is essential.

Nurses are generally responsible for administering medication to patients and are, therefore, able to monitor or report medication errors. However, nurses can sometimes be responsible for causing errors, so it is important that they understand the consequences of these mistakes and how to prevent them. This article reports the results of a study that analysed the views of nurses, pharmacists and physicians at a Finnish university hospital on the prevention of medication errors. The findings suggest errors can be prevented by improving work environments and allowing healthcare staff, particularly nurses, to concentrate on the task at hand when dealing with medicines.

Tässä tutkimuksessa tarkastellaan ohjelmistokehittäjäryhmän sisäisen dokumentaation saavutettavuutta kohdeyrityksessä. Tutkimuksen tavoitteena on kartoittaa kohdeyrityksen sisäisten dokumenttien käyttäjien ja sisällöntuottajien kokemuksia sisäisten dokumenttien käytöstä, tutkia saavutettavuuteen liittyviä ongelmia sekä kehittää ratkaisuja siinä havaittuihin ongelmiin. Tutkimushypoteesit olivat seuraavat: Sisäisten dokumenttien käyttäjillä ja sisällöntuottajilla on hyvin erilaisia tarpeita ja näkemyksiä sisäisestä dokumentaatiosta, eivätkä käyttäjät ja sisällöntuottajat ole yhtä mieltä sisäisen dokumentaation tarpeellisuudesta. Sisäisten dokumenttien käyttäjät ja sisällöntuottajat eivät ole tietoisia toistensa tarpeista eivätkä ole yhtä mieltä siitä, miten sisäistä dokumentointia pitäisi kehittää. Tutkimus on aineistolähtöinen, ja tutkimuksen aihe ja tutkimuskysymykset on määritelty aineistosta nousseiden huomioiden perusteella. Tutkimuksessa käytetty pääasiallinen aineisto kerättiin ohjelmistokehittäjäryhmän jäseniltä puolistrukturoituja haastatteluja käyttäen (n=26). Toissijaisena aineistona käytettiin materiaalia, joka kerättiin dokumentoinnista ja informaation suunnittelusta vastaavan henkilökunnan kanssa käydyistä keskusteluista. Tutkimus nojautuu toimintatutkimuksen metodologiaan ja periaatteisiin. Toimintatutkimuksen periaatteiden mukaisesti informantteja kohdeltiin osallistujina, jotka ovat tutkijan kanssa samanarvoisessa asemassa, ja projektin aikana pyrittiin lisäämään kaikkien tutkimukseen osallistuneiden henkilöiden kokonaisvaltaista ymmärrystä tutkimusaiheesta. Tutkimuksessa pyrittiin luomaan keskustelua sisäisen dokumentaation käyttäjien ja sisällöntuottajien välille sekä edistämään osallistujien mahdollisuuksia vaikuttaa sisäisen dokumentoinnin prosessiin työpaikalla. Tutkimusaineiston perusteella näyttäisi, että sisäisen dokumentaation käyttäjien ja sisällöntuottajien kokemukset sisäisten dokumenttien käytöstä ja niiden saavutettavuudesta ovat suurelta osin negatiivisia. Sisäisten dokumenttien saavutettavuudessa on ongelmia, jotka liittyvät epätarkasti määriteltyihin dokumentoinnin konventioihin, sisällöntuottajien työtapoihin ja dokumentoinnin taitotasoon, dokumentointityökalun toimivuuteen sekä dokumentoinnin hallintaan ja ohjaukseen ohjelmistokehittäjäryhmässä. Teknisen viestinnän tehtäviä ja niiden merkitystä ei tunneta ohjelmistokehittäjäryhmässä tarpeeksi hyvin, ja ryhmä näyttäisi tarvitsevan teknisen kirjoittajan koordinoimaan sisäistä dokumentointia. Sisäisen dokumentoinnin prosessi, sisällöntuottajien dokumentaatioon liittyvät työtehtävät ja informaation suunnittelu täytyisi määritellä uudelleen sisäisen dokumentaation käyttäjien näkökulmasta, ja dokumentoinnin prosessia täytyisi ohjata huolellisesti määritellyn prosessin mukaisesti. Tämän tutkimuksen tulokset vahvistavat aiemmissa tutkimuksissa todettuja puutteita teknisen viestinnän ammattitaidon arvostuksesta yrityksissä ja tieto-organisaatioissa. Tutkimuksen tulokset ovat hyödyllisiä yrityksille, jotka pyrkivät löytämään mahdollisimman toimivan tavan tuottaa saavutettavaa sisäistä dokumentaatiota.

In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments.

Effects of various beta-carbolines (BC's) and two tetrahydroisoquinolines (TIQ's) on the specific binding of a natural opiate delta-receptor ligand, leucine enkephalin, have been studied in rat synaptosomal membranes, and compared with the effects on the binding of mu-receptor ligands dihydromorphine and naloxone. Harmaline (7-MeO-1-Me-dihydro-BC) was the most potent compound studied (Ki value 3.5 microM), while the two TIQ's (salsolinol and salsolidine) were less potent than BC's (Ki greater than 100 microM) in inhibiting the binding of delta-receptors. In general, BC's showed more affinity for delta-receptors than for mu-receptors; salsolinol was more potent against the binding of mu-receptors. Inhibition of binding was generally of the competitive type: Kd values increased and Bmax values were not altered. The Na dependence suggests that BC's and salsolinol are antagonists or partial agonists of opioids. Since the binding affinity of BC's and TIQ's was on the micromolar level only, the opiate receptors do not appear to be the major sites of action for BC's or TIQ's.

Plasma levels of diazepam and its metabolites were compared after a controlled release formulation and a regular tablet. Both gas chromatographic analysis of plasma diazepam and desmethyldiazepam and radioreceptor assay of total benzodiazepine activity were used. Also the concentrations of benzodiazepine in saliva samples were analyzed by radioreceptor assay. A typical initial plasma peak was seen after the regular tablet but not after the controlled release capsule. Hence the excessive initial sedation can be avoided and the risk of abuse reduced. Desmethyldiazepam increased for about two days after a single dose of diazepam. The receptor assay correlated in general with the sum of diazepam and its desmethyl derivative. The saliva assay gave about 2.5% of the plasma total benzodiazepine which correlates well with the expected free benzodiazepine. It seems that both the plasma radioreceptor assay and the saliva assay can be used to monitor the total benzodiazepine concentration.

The objectives of our study were to explore the barriers, preferences and attitudes of the pharmaceutical industry towards conducting clinical trials in Finland. In-depth semi-structured interviews were conducted with 18 representatives of the pharmaceutical industry with different amounts of experience of clinical trials. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Overall, the respondents had a positive attitude towards conducting clinical trials in Finland. The major barriers seemed to occur at the beginning of the trial and mostly consisted of bureaucratic obstacles. The informants hoped for a more positive attitude of the public sector, more flexibility in hospitals and professionalism in practical implementation, e.g. having special research centres or site management services. The most dismotivating factors were the high costs and the constraints imposed by bureaucracy. The variety in practices of local ethics committees was considered problematic, and the need for common standard operating procedures was pointed out. The smallest barriers were encountered in subject recruitment by the investigators and their clinical work, documentation, investigational product logistics and communication with the regulatory authorities. The quality, know-how and reliability of the study personnel, the tightening of time lines in general, an investigator register/pool and collaboration with media in disseminating information about clinical trials to the general public were reported as the most appealing factors. Training in GCP, mainly incorporated in the medical education programme, and a certificate or equivalent were generally considered necessary, though a voluntary system was preferred. The barriers and preferences pointed out suggest various improvements and ways to produce high-quality, GCP-compliant clinical drug research and to ensure the availability of sufficient conditions to carry out clinical trials also in the future.

Archaea colonising defined compartments of Scots pine Suillus bovinus or Paxillus involutus mycorrhizospheres developed in forest humus-containing microcosms were investigated by nested polymerase chain reaction (PCR), cloning, restriction fragment length polymorphism (RFLP) and sequencing. Archaea representing six RFLP groups were detected in the system. Sequence analysis of clones representing the different RFLP types confirmed the presence of novel Finnish forest soil Crenarchaeota. Archaeal sequences were identified from mycorrhizas of both P. involutus and S. bovinus, at the margins of the external mycelium and in uncolonised humus but not from non-mycorrhizal short roots. Fungal and compartment-specific crenarchaeal occupation of mycorrhizospheres is discussed in relation to bacterial community distribution in similar systems.

Introduction There are concerns that the high incidence of medicine-related adverse events is compromising patient safety. System errors and human factors, particularly inadequate knowledge of pharmacotherapy, are significant causes of medication errors. Little has been published on the continuing professional education of radiographers. We report on a study undertaken in Finland between 2012 and 2014. Methods In this quasi-experimental study, we explored the relationship between radiographers' backgrounds (e.g., age, clinical experience, sex) and intravenous (IV) medication theoretical competence before (n = 77) continuing pharmacotherapy education delivered with two different learning methods, 1 to 2 weeks after (n = 56) and 6 months later (n = 37). Results After the education programs, younger age, less clinical experience, and education in higher education institute (University of Applied Sciences) were significantly associated with performing better than average (more than median score) in the IV pharmacotherapy knowledge test. Both immediately after education and 6 months later, more participants performed better than average and passed more than 80% of correct answers limit after simulation-based than web-based education, respectively. Discussion Continuing IV pharmacotherapy education improved theoretical medication competence, particularly for younger and less experienced radiographers. Evidence-based continuing education for radiographers is needed to assure patient safety.

C . A B R E U , G . J U R G E N S , P . D E M A R C O , A . S A A N O A N D A . A . B O R D A L O . 2001. Aims: Application of molecular techniques to ecological studies has unveiled a wide diversity of micro-organisms in natural communities, previously unknown to microbial ecologists. New lineages of Archaea were retrieved from several non-extreme environments, showing that these micro-organisms are present in a large variety of ecosystems. The aim was therefore to assess the presence and diversity of Archaea in the sediments of the river Douro estuary (Portugal), relating the results obtained to ecological data. Methods and Results: Total DNA was extracted from sediment samples obtained from an estuary deprived of vegetation, amplified by PCR and the resulting DNA fragments cloned. The archaeal origin of the cloned inserts was checked by Southern blot, dot blot or colony blot hybridization. Recombinant plasmids were further analysed by restriction with AvaII and selected for sequencing. Phylogenetic analyses of 14 sequences revealed the presence of members of the domain Archaea. Most of the sequences could be assigned to the kingdom Crenarchaeota. Conclusions: Most of these sequences were closely related to those obtained from nonextreme Crenarchaeota members previously retrieved from diverse ecosystems, such as freshwater and marine environments. Significance and Impact of the Study: The presence of archaeal 16S rDNA sequences in temperate estuarine sediments emerges as a valuable contribution to the understanding of the complexity of the ecosystem.

An anaerobic, 2,4,6-trichlorophenol ortho-dehalogenating mixed culture was enriched from sediment of the river Saale (Germany). Two isolated dechlorinating colonies (MK1 and MK2) consisted of rods of different lengths and thicknesses, indicating heterogeneity. Following subcultivation with thiosulfate as alternative electron acceptor and cocultivation with Clostridium celerecrescensT, the 2,4,6-trichlorophenol-dehalogenating bacterium Desulfitobacterium frappieri strain TCP-A was isolated and characterized regarding its taxonomic properties and the spectrum of chlorophenols that it dehalogenated. Four other bacterial strains were coenriched and identified as organisms with closest phylogenetic relatedness to the Clostridium type strains C. indolis, C. glycolicum, C. hydroxybenzoicum and C. sporosphaeroides (16S rDNA sequence identities of 99.5, 99.2, 94.4, and 93.5%, respectively). Amplified ribosomal DNA restriction analysis of the original dehalogenating cultures MK1 and MK2 (when not exposed to thiosulfate) confirmed the microbial heterogeneity and revealed the presence of two additional species related to the type strains of C. celerecrescens and Clostridium propionicum. Only one copy of the 16S rRNA genes of Desulfitobacterium frappieri in each of the clone libraries of MK1 and MK2 (containing 136 and 56 clones, respectively) was found by dot-blot hybridization, suggesting a relatively low number of the dehalogenating bacterium within the enrichment culture.

We report here on novel groups of Archaea in the bacterioplankton of a small boreal forest lake studied by the culture-independent analysis of the 16S rRNA genes amplified directly from lake water in combination with fluorescent in situ hybridization (FISH). Polymerase chain reaction products were cloned and 28 of the 160 Archaea clones with around 900-bp-long 16S rRNA gene inserts, were sequenced. Phylogenetic analysis, including 642 Archaea sequences, confirmed that none of the freshwater clones were closely affiliated with known cultured Archaea. Twelve Archaea sequences from lake Valkea Kotinen (VAL) belonged to Group I of uncultivated Crenarchaeota and affiliated with environmental sequences from freshwater sediments, rice roots and soil as well as with sequences from an anaerobic digestor. Eight of the Crenarchaeota VAL clones formed a tight cluster. Sixteen sequences belonged to Euryarchaeota. Four of these formed a cluster together with environmental sequences from freshwater sediments and peat bogs within the order Methanomicrobiales. Five were affiliated with sequences from marine sediments situated close to marine Group II and three formed a novel cluster VAL III distantly related to the order Thermoplasmales. The remaining four clones formed a distinct clade within a phylogenetic radiation characterized by members of the orders Methanosarcinales and Methanomicrobiales on the same branch as rice cluster I, detected recently on rice roots and in anoxic bulk soil of flooded rice microcosms. FISH with specifically designed rRNA-targeted oligonucleotide probes revealed the presence of Methanomicrobiales in the studied lake. These observations indicate a new ecological niche for many novel 'non-extreme' environmental Archaea in the pelagic water of a boreal forest lake.

The feasibility of the water-activated, pH-controlled silicone reservoir devices for transdermal administration was investigated using timolol maleate as a model drug. Timolol patches were applied to the arm of 12 volunteers for 81 h, two patches per subject. Timolol absorption from patches was compared to that from a peroral timolol tablet formulation (Blocanol((R)) 10 mg). Furthermore, in vivo plasma levels of timolol were compared with those predicted by kinetic simulations. Skin irritation induced by timolol patches was assessed by visual scoring and color reflectance measurements. With water-activated, pH-controlled patches both steady-state concentrations of timolol in plasma and its duration could be controlled. However, a considerable, inter-individual variability in the transdermal absorption of timolol was observed. This is due to the high fractional skin control in timolol delivery. Timolol patches were well tolerated by subjects. Skin irritation induced by the combination of timolol with long-term occlusion was mild, and after removal of the patches, skin changes were practically reversed in 24 h. Simulation model was useful in prediction of timolol levels in plasma after transdermal administration.

Genetic diversity of forest soil Archaea was measured by extraction of total DNA from forest soil samples followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Southern blot hybridization and phylogenetic analysis of archaeal 16S rDNA. Soil samples from boreal forest treated with two regeneration practices were studied: clear-cutting (A) and clear-cutting followed by prescribed burning (B) 2 years later. The samples collected 1 year after the prescribed burning included a control soil (C) from an untreated standing forest. The PCR products from the three different soil samples were cloned and analyzed by RFLP. Soil samples A, B and C gave eight, nine and six different restriction profiles, respectively. New electrophoreses were run with clones of different digestion patterns, followed by Southern blotting and DNA hybridization with two different Crenarchaeota-specific oligonucleotide probes. Selected clones were sequenced and phylogenetically characterized. It was discovered that the clones from soils A and B are similar and differ from the clones isolated from the control soil C. Both the RFLP-hybridization study of the clones and phylogenetic analysis of selected sequences from all three types of soil supported the division of the new Crenarchaeota into two subgroups. It is shown that the RFLP-hybridization technique can be successfully used for preliminary evaluation of clone diversity in the rDNA library.

The structure and function of ciliated epithelium were studied in 44 human nasal mucosa samples using a photoelectric method and scanning electron microscopy (SEM). The ciliary beat frequency (CBF) of cases with recurrent or chronic sinusitis was 9.1 +/- 5.4 Hz. In eight of the samples (18.2%) no ciliary activity was detected. The amount of ciliated cells, the orientation of cilia, epithelial metaplasia, and secretion were found to be explanatory factors accounting for the decreased ciliary activity. Ciliary disorientation and a lack of ciliated cells in SEM correlated with low ciliary activity. In cases where sinusitis secretion was not seen, the CBF was slower than in cases with mucus or mucopurulent secretion. Sinusitis with disoriented cilia, a loss of ciliated cells, and a lack of mucosal secretion is associated with a decreased CBF. This may lead to impaired mucociliary clearance and increase the risk of recurrent and chronic sinusitis.

SUMMARY 1. In the present study on guinea-pig tracheal epithelium, the influence of age on ciliary beat frequency (CBF) was investigated. 2. An age-dependent decrease in CBF was seen: as the age of the guinea-pig increased from 0.9 to 16.3 months, CBF decreased from 20.2 to 6.9 Hz. 3. The effect of leukotriene D4 (LTD4) on CBF was also examined using tracheal explants from guinea-pigs of varying ages. The lower CBF of the older animal was increased by LTD4 to a larger extent than was the higher CBF seen in explants taken from younger animals. 4. Ciliary activity and possibly also the sensitivity of the cilia to drugs, seems to be dependent upon the age of the animal, which has to be taken into consideration when comparing the results of different studies on the effects of xenobiotics on mucociliary function.

The aim of this paper is to analyse how medication incidents are detected in different phases of the medication process. The study design is a retrospective register study. The material was collected from one university hospital's web-based incident reporting database in Finland. In 2010, 1617 incident reports were made, 671 of those were medication incidents and analysed in this study. Statistical methods were used to analyse the material. Results were reported using frequencies and percentages. Twenty-one percent of all medication incidents were detected during documenting or reading the documents. One-sixth of medication incidents were detected during medicating the patients, and approximately one-tenth were detected during verifying of the medicines. It is important to learn how to break the chain of medication errors as early as possible. Findings showed that for nurses, the ability to concentrate on documenting and medicating the patient is essential.

Nurses are generally responsible for administering medication to patients and are, therefore, able to monitor or report medication errors. However, nurses can sometimes be responsible for causing errors, so it is important that they understand the consequences of these mistakes and how to prevent them. This article reports the results of a study that analysed the views of nurses, pharmacists and physicians at a Finnish university hospital on the prevention of medication errors. The findings suggest errors can be prevented by improving work environments and allowing healthcare staff, particularly nurses, to concentrate on the task at hand when dealing with medicines.

Leukotriene D4 (LTD4) is a potent bronchoconstrictor and inflammatory mediator in asthma. Data concerning the effects of LTD4 on ciliary function in the respiratory tract are sparse and contradictory. The purpose of the present study was to clarify the effects of LTD4 on mucociliary activity using the tracheal mucosa of two laboratory animal species, guinea-pig and rat, as well as human nasal mucosa. The ciliary beat frequency (CBF) was measured photoelectrically and determined by Fast Fourier Transform computer analysis. Additionally the structure of ciliated epithelia of guinea-pig trachea after LTD4-immersion was investigated using a scanning electron microscope (SEM). In all tissues, LTD4 increased CBF showing a bell-shaped dose-response curve. The maximum effect was 75 +/- 30% in guinea-pig at 10(-9) mol/l, 119 +/- 49% in rat at 10(-7) mol/l, and 86 +/- 28% at 10(-6) mol/l in human tissue. In guinea-pig tracheal mucosa, there was an indication of an increase in the amount of mucus and disorientation of cilia were seen by SEM after immersion in LTD4. These findings suggest that LTD4 stimulates ciliary activity, but impairs the orientation of cilia.

Many preservatives commonly included in nasal drops and sprays are known to impair mucociliary clearance. We studied the effects of four frequently used preservatives on ciliary beat frequency (CBF) in respiratory tissue. Sodium metabisulfite and chlorbutol did not change the CBF at concentrations up to 50 mg/L in rat tracheal mucosa. Chlorocresol 25 mg/L and 50 mg/mL reversibly decreased CBF (by 33% and 68%, respectively) in 60 minutes. Benzalkonium chloride impaired CBF irreversibly already at a relatively low concentration (12.5 mg/L). To further clarify these results, we studied the effects of the most ciliotoxic (benzalkonium chloride) and nonciliotoxic (chlorbutol) preservative on guinea pig tracheal epithelium and human nasal mucosa. Although chlorbutol had no effect on the CBF, a dose-dependent decrease on CBF was seen in guinea pig and human ciliated epithelium during their immersion in benzalkonium chloride. At a concentration of 50 mg/L it stopped the ciliary activity in 40 minutes in guinea pig trachea, and in human nasal mucosa, benzalkonium chloride concentrations of 25 and 50 mg/L, decreased the CBF irreversibly (by 28% and 60%, respectively) in 60 minutes. These results suggest that chlorbutol is a safe and well tolerated preservative. Banzalkonium chloride is ciliostatic in vitro to rat, guinea pig, and human respiratory mucosa. Therefore, prolonged clinical use of benzalkonium chloride may impair mucociliary clearance, a major defense respiratory mechanism.

The combined and separate effects of Cd and wood ash on Archaea from coniferous forest humus were studied in a microcosm experiment. Nonmetric multidimensional scaling of the denaturing gradient gel analysis of polymerase chain reaction amplified 0.9 kb 16S ribosomal DNA fragments revealed changes in archaeal communities due to the ash treatments. Cd with or without ash did not further influence the result. Representatives of the ash and control communities were cloned, grouped by restriction fragment length polymorphism analysis and finally sequenced. All sequences belonged to non-thermophilic Crenarchaea.

Effect of triethyllead on the specific [3H]flunitrazepam binding was studied in rat cortical and cerebellar P2 fractions in vitro and in tissue homogenates of several rat brain regions ex vivo after 5 daily subcutaneous doses of 1.9 mg/kg triethyllead acetate to rats. Up to concentration of 100 microM, triethyllead did not affect significantly the specific [3H]flunitrazepam binding but attenuated marginally (14-18%) the GABAA receptor agonist, muscimol-induced elevation of [3H]flunitrazepam binding in cerebellar tissue. After the subacute treatment of rats with triethyllead, the specific [3H]flunitrazepam binding was 27% lower in cerebellum compared to control animals. In other brain regions the receptor binding was not changed. The data suggest that triethyllead modified the cerebellar GABAA receptor complex causing decreased binding in the benzodiazepine site. Such an inhibitory effect in the GABAA receptor complex may decrease cerebellar inhibitory output and augment the triethyllead induced convulsions and tremor.

Objective: To investigate the use of benzodiazepines (BD) in relation to the risk of falling injuries in an elderly population (65 yrs. or older) Design: An unmatched case-control study. Setting: The town of Pori, Finland Participants: 380 subjects aged 65 years or over, who presented for medical treatment due to a fall during the 12 months from Sept. 1987 to Aug. 1988, and 342 controls, 65 years or older, selected from the population register. The control subjects were examined according to a schedule that corresponded in time (time of day, day of the week and month) to the time-distribution of falls in an earlier study Outcome measure: All falls leading to medical treatment. BD use was determined from the serum, and the type of BD was determined by interviews and controlled from patient records Results: We found a tendency toward a dose-response relationship between the serum BD concentration and the occurrence of falling injury. The risk of faling injury related to short-acting BDs was increas...

1. The ciliary beat frequency (CBF) of six animal species from six regions of the respiratory tract were measured: inferior turbinate, nasopharynx, the upper part of trachea from first to second cartilage, the lower part of trachea, main bronchus and subsegmental bronchi. Cow, pig, dog, rabbit, guinea-pig and rat were studied. 2. There were no significant differences in the CBF values between cow, pig and dog, and the ciliary activity was essentially the same (11.3-16.9 Hz) in all parts of the respiratory tract. 3. In the rat, the CBF was slower, especially in subsegmental bronchi (6.8 Hz). 4. In general, CBF was higher in upper than lower airways, with the exception of guinea-pig. 5. Signal quality was the highest in guinea-pig tissue, whereas rat tissue produced the signal with the widest variation in CBF and the highest proportion of distorted waveforms. 6. Therefore, for studying drug effects on ciliary activity, guinea-pig seems to be a more suitable animal than the more commonly used rabbit or rat. In drug comparisons, the same part of the respiratory tract and the same animal species should be used.

Timolol eyedrops may cause systemic side-effects in glaucoma patients due to absorption of the drug into systemic circulation. In a previous study, timolol concentrations in plasma were reduced if timolol was administered in ocular inserts instead of eyedrops. We compared the intraocular pressure lowering effect and systemic absorption of timolol inserts to those of 0.5 % timolol eyedrops in humans. Inserts of silicone tubing released 90.3 ± 13.9 µg of timolol in 24 hours in vivo. Timolol inserts afforded similar decreases in intraocular pressure in open-angle glaucoma patients as did b.i.d. eyedrops, but produced lower peak timolol concentrations in plasma, 0.70 ± 0.10 ng/ml and 0.24 ± 0.05 ng/ml, respectively. After eyedrops, peak concentrations were achieved at 15.0 ± 2.2 min, while application of an insert resulted in a delayed peak (tmax = 623 ± 195 min). The insert resulted in a higher systemically absorbed fraction of the timolol dose than the eyedrop, but the peak timolol concentration and daily absorbed amount of timolol were decreased. The release rate of timolol from the inserts in vivo was only slightly less than that in vitro. Silicone devices are useful for clinical testing of controlled delivery properties of ocular drugs.

Isolates of actinomycetes (19 strains) and fungi (12 strains) obtained from houses with microbial indoor air problems were tested for antifungal, antibacterial and genotoxic properties. The tests were performed by observing the inhibition zones on the lawn of indicator organisms around agar discs cut from confluent plates of the test strains. A yeast ( Candida albicans ), a mold ( Alternaria brassicicola ) and a Gram-positive bacterium ( Streptococcus salivarius subsp. thermophilus ) were used as indicator organisms for general antifungal and antibacterial properties, while genetoxicity was detected with a DNA repair-deficient Escherichia coli strain CM871. Among the actinomycetes there were four antifungal, eight antibacterial and two genotoxic isolates, while one antibacterial, one antifungal and three genotoxic strains were detected among the fungi. Multiple activities were detected in two actinomycetes and two fungal isolates. Three bioactive actinomycetes were also examined for the inhibition of the ciliary beating frequency (CBF) of isolated guinea pig mucosal explants, and one of the strains was positive in this test.

In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments.

Diseases and medications associated with the occurrence of falls leading to medical treatment in elderly Finns (65 yrs or older) during a one-year period are presented. The design was that of a case-control study involving 380 fallers seeking medical treatment and 342 unmatched controls selected randomly from the population register. The occurrence of a fall was shown by logistic regression analysis to be related to advanced age, presence of benzodiazepine in the serum, hypertrophy of the prostate, poor mental capacity, presence of chronic lung disease and asthma, use of analgesies and use of digitalis in the men, and to advanced age, poor mental capacity, presence of benzodiazepine in the serum, use of analgesies and non-occurrence of lower limb arthrosis in the women. The corresponding log-linear models showed advanced age and the presence of benzodiazepine in the serum to be independent risk factors for falling both in the men and women. Furthermore, the use of analgesies was related to falling in the women with normal mental capacities. No disease was independently associated with falls. The results suggest caution in the use of benzodiazepines among the elderly.

Chinoin-170 (Ch-170; 3,7-dihydro-1,3-dimethyl-7-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]1H-purine-2,6-dione) is a new antitussive with bronchodilating activity. Its effects on the ciliary beating frequency (CBF) and mucociliary clearance were studied. In tracheal explants of rats, Ch-170 dose-dependently at concentrations 2 and 5 mg mL−1 depressed CBF by 24 and 33%, respectively. In human mucosal explants, however, no effects were seen at concentrations up to 5 mg mL−1. In anaesthetized guinea-pigs, an intravenous 50 mg kg−1 dose of Ch-170 caused no changes, and 100 mg kg−1 increased the CBF by 15%. Intravenous Ch-170 dose-dependently increased by 93 (50 mg kg−1), 179 (70 mg kg−1) and 253% (100 mg kg−1) the tracheobronchial mucociliary clearance in rabbits. The effect, studied using 99mTc-labelled red blood cells as a marker, was of similar quantity to that brought about by administering 16, 25 and 40 mg kg−1 doses of bromhexine. It is concluded that unlike many older antitussives, Ch-170 in-vitro only slightly decreases the CBF in rats and has no adverse effects on the CBF in human mucosal explants at concentrations up to 5 mg mL−1. In-vivo, Ch-170 does not significantly alter the CBF in guinea-pigs, but dose-dependently increases the mucociliary clearance in rabbits. The increase is most probably a result of changes in the production and the properties of respiratory mucus.

1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study. 2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 ± 0.7 min and 37.8 ± 2.5 min. 3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00–0.22%. 4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects. 5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.

The effect of oxcarbazepine (OCBZ) on the kinetics of an oral contraceptive containing ethinyloestradiol (EE) and levonorgestrel (LNG) was investigated in 13 healthy female volunteers who had previously received the contraceptive for at least 3 months. After 15 days of the first study cycle, each subject received, in addition to the oral contraceptive, 300 mg OCBZ on day 16, 300 mg twice daily on day 17, and 300 mg three times daily from day 18 of the first cycle to day 18 of the next menstrual cycle. The area under the curve values for both EE and LNG decreased when OCBZ was given with the oral contraceptive (p = 0.006, analysis of variance). The results indicate that OCBZ, like most antiepileptic drugs (AEDs), decreases the bioavailability of EE and LNG, perhaps by affecting metabolism or protein binding.

Non-radioactive DNA-DNA-hybridization was applied to identify Rhizobium galegae from l g soil samples. Total bacterial DNA from the samples was extracted using lysozyme and a freeze-thaw procedure and the sample DNA was attached to nitrocellulose or nylon membranes. During a 3 h hybridization 10 pg of sample DNA could be detected on a nylon filter with digoxigenin-dUTP-labelled R. galegae total DNA. The sensitivity was the same for either the colour-based or the chemiluminescence detection techniques.

The affinity of strychnocarpine and related β-carbolines for serotonin, benzodiazepine, tryptamine, opiate and GABA receptors in rat brain was studied. Strychnocarpine showed a low to very low affinity for all the receptors tested. The weak binding to tryptamine receptors might explain part of the tremorigenic effects found earlier in the in vivo studies.

The pharmacokinetics of two 200 mg ibuprofen (IP) film-coated tablets and a 200 mg effervescent tablet were studied in cross-over fashion on 14 healthy volunteers. After ingestion of the novel film-coated tablet, absorption half life (0.6 h) was 42-50 % (p

Summary Objectives: In paediatric pharmacotherapy, many drugs are prescribed to be given in ways and for conditions not approved in the marketing authorization (MA). Thus, off-label prescribing of drugs with no MA is widespread in paediatric wards. However, drug MA status and clinical practices differ across countries. In this prospective study, we studied the prescribing of off-label and unlicensed drugs in three paediatric wards in a tertiary hospital in Finland. Furthermore, we reviewed previous published studies to provide an up-to-date international perspective on prescribing of off-label and unlicensed drugs for hospitalized children. Methods: During a 2-week period, prescriptions for patients under 18 years of age (median age 1·6 years) in three wards; neonatal intensive care unit (NICU), general paediatric ward and paediatric surgical ward were recorded daily and drug-licensing status of all prescriptions was determined according to the approved summary of product characteristics. Published studies were retrieved through electronic searches, including MEDLINE (PubMed). Results: Of the 141 children, 108 received 629 prescriptions. Of the 108 children with a prescription, 82 (76%) had at least one off-label or unlicensed drug prescribed; 79% in the NICU, 63% in the general ward and 91% in the surgical ward (P = 0·014). Of the 108 children with a prescription, 26 (24%) received prescriptions for licensed drugs, 71 (66%) received prescriptions off-label and 36 (33%) for unlicensed drugs. Of all 629 prescriptions, 321 (51%) were for licensed drugs, 226 (36%) for off-label and 82 (13%) for unlicensed drugs. International studies showed similar extents of off-label and unlicensed-drug prescribing. Conclusion: This study indicates that the use of off-label and unlicensed drugs is widespread in all the different paediatric wards surveyed and was as extensive as those reported for other countries.

The effect of the intravenous administration of ATP on the airway ciliary beating frequency (CBF) of anaesthetized rat was studied by measuring CBF photoelectrically from the inner surface of incised trachea. ATP (1 or 10 mg/kg) caused no changes in the CBF, but the decrease in CBF, which was seen after 70 min. in control rats, was abolished by ATP (10 mg/kg). ATP acutely decreased blood pressure; at 10 mg/kg, the decrease was 70 mmHg in systolic, and 60 mmHg in diastolic blood pressure. ATP also tended to increase rectal temperature and airway resistance, but these effects were not significant. ECG remained normal. Intravenous administration of ATP helps to maintain the function of tracheal cilia in anaesthetized rats at doses that, although lower blood pressure, do not cause fatal untoward effects.

Objective: To explore investigator barriers, preferences, and attitudes towards conducting clinical trials in Finland. Method: In‐depth, semi‐structured interviews with 20 clinicians working in the field of cardiovascular medicine were performed. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Twenty clinicians from all (five) university hospitals in Finland and from three subgroups: 1) with long experience, 2) with limited experience and 3) reluctant to carry out clinical trials, were sampled purposefully. Main outcome measures: Barriers and (de)motivating factors in carrying out clinical trials and need for training in Good Clinical Practice (GCP).Results: Overall, the investigators had a positive attitude towards conducting clinical trials. The major barriers seemed to occur at the beginning of the trial: bureaucracy, lack of time and laboriousness. The informants hoped for more specific in‐house rules and flexibility in hospitals. The greatest investigator barriers were insufficient financial incentives, trial‐related reasons and administrative affairs/bureaucracy. The smallest barriers were reported in subject recruitment, clinical work, documentation, investigational product logistics and communication with ethics committees. Financial incentives, a possibility to incorporate a personal sub‐study or other benefits for personal research and scientific and clinical interest in the trial were reported as the most motivating factors. Carrying out studies in practice and an opportunity to participate in a trial during one's postgraduate specialist education were considered beneficial. Training in GCP, mainly in the course of postgraduate education, and a certificate or equivalent were generally considered necessary, although a voluntary system was preferred.Conclusion: The interviews of clinicians provide valuable information about the barriers and preferences related to the practical implementation of clinical trials. If the trial is scientifically/clinically interesting and involves a small administrative burden and sufficient financial compensation, investigators are motivated to participate. The barriers and preferences should be considered in decision‐making, to meet the various needs of all parties involved and to produce high‐quality GCP‐compliant clinical drug research. This would ensure the availability of sufficient conditions to carry out clinical trials also in the future.