The roughness and imaging characterisation of different pharmaceutical surfaces

The surface properties of solid state pharmaceutics are of critical importance. Processing modifies the surfaces and effects surface roughness, which influences the performance of the final dosage form in many different levels. Surface roughness has an effect on, e.g., the properties of powders, tablet compression and tablet coating. The overall goal of this research was to understand the surface structures of pharmaceutical surfaces. In this context the specific purpose was to compare four different analysing techniques (optical microscopy, scanning electron microscopy, laser profilometry and atomic force microscopy) in various pharmaceutical applications where the surfaces have quite different roughness scale. This was done by comparing the image and roughness analysing techniques using powder compacts, coated tablets and crystal surfaces as model surfaces. It was found that optical microscopy was still a very efficient technique, as it yielded information that SEM and AFM imaging are not able to provide. Roughness measurements complemented the image data and gave quantitative information about height differences. AFM roughness data represents the roughness of only a small part of the surface and therefore needs other methods like laser profilometer are needed to provide a larger scale description of the surface. The new developed roughness analysing method visualised surface roughness by giving detailed roughness maps, which showed local variations in surface roughness values. The method was able to provide a picture of the surface heterogeneity and the scale of the roughness. In the coating study, the laser profilometer results showed that the increase in surface roughness was largest during the first 30 minutes of coating when the surface was not yet fully covered with coating. The SEM images and the dispersive X-ray analysis results showed that the surface was fully covered with coating within 15 to 30 minutes. The combination of the different measurement techniques made it possible to follow the change of surface roughness and development of polymer coating. The optical imaging techniques gave a good overview of processes affecting the whole crystal surface, but they lacked the resolution to see small nanometer scale processes. AFM was used to visualize the nanoscale effects of cleaving and reveal the full surface heterogeneity, which underlies the optical imaging. Ethanol washing changed small (nanoscale) structure to some extent, but the effect of ethanol washing on the larger scale was small. Water washing caused total reformation of the surface structure at all levels.

Suomen rautakautiset kulkuset, kellot ja kelloriipukset : äänimaiseman arkeologiaa

The thesis addresses the problem of Finnish Iron Age bells, pellet bells and bell pendants, previously unexplored musical artefacts from 400–1300 AD. The study, which contributes to the field of music archaeology, aims to provide a gateway to ancient soundworlds and ideas of music making. The research questions include: Where did these metal artefacts come from? How did they sound? How were they used? What did their sound mean to the people of the Iron Age? The data collected at the National Museum of Finland and at several provincial museums covers a total of 486 bells, pellet bells and bell pendants. By means of a cluster analysis, each category was divided into several subgroups. The subgroups, which all seem to have a different dating and geographical distribution, represent a spread of both local and international manufacturing traditions. According to an elemental analysis, the material varies from iron to copper-tin, copper-lead and copper-tin-lead alloys. Clappers, pellets and pebbles prove that the bells and pellet bells were indisputably instruments intended for sound production. Clusters of small bell pendants, however, probably produced sound by jingling against each other. Spectrogram plots reveal that the partials of the still audible sounds range from 1 000 to 19 850 Hz. On the basis of 129 inhumation graves, hoards, barrows and stray finds, it seems evident that the bells, pellet bells and bell pendants were fastened to dresses and horse harnesses or carried in pouches and boxes. The resulting acoustic spaces could have been employed in constructing social hierarchies, since the instruments usually appear in richly furnished graves. Furthermore, the instruments repeatedly occur with crosses, edge tools and zoomorphic pendants that in the later Finnish-Karelian culture were regarded as prophylactic amulets. In the Iron Age as well as in later folk culture, the bell sounds seem to have expressed territorial, social and cosmological boundaries.

Stalking and violence victimization among Finnish university students

This study examined the nature and lifetime prevalence of two types of victimization among Finnish university students: stalking and violence victimization (i.e. general violence). This study was a cross-sectional study using two different datasets of Finnish university students. The stalking data was collected via an electronic questionnaire and the violence victimization data was collected via a postal questionnaire. There were 615 participants in the stalking study (I-III) and 905 participants in the violence victimization study. The thesis consists of four studies. The aims regarding the stalking substudies (Studies I-III) were to examine the lifetime prevalence of stalking among university students and to analyze how stalking is related to victim and stalker characteristics and certain central variables of stalking (victim-stalker relationship, stalking episodes, stalking duration). Specifically, the aim was to identify factors that are associated with stalking violence and to factors contributing to the stalking duration. Furthermore, the aim was also to investigate how university students cope with stalking and whether coping is related to victim and stalker background characteristics and to certain other core variables (victim-stalker relationship, stalking episodes, stalking duration, prior victimization, and stalking violence). The aims for the violence victimization substudy (Study IV) were to examine the prevalence of violence victimization, i.e. general violence (minor and serious physical violence and threats) and how violence victimization is associated with victim/abuser characteristics, symptomology, and the use of student health care services. The present study shows that both stalking and violence victimization (i.e. general violence) are markedly prevalent among Finnish university students. The lifetime prevalence rate for stalking was 48.5% and 46.5% for violence victimization. When the lifetime prevalence rate was restricted to violent stalking and physical violence only, the prevalence decreased to 22% and 42% respectively. The students reported exposure to multiple forms of stalking and violence victimization, demonstrating the diversity of victimization among university students. Stalking victimization was found to be more prevalent among female students, while violence victimization was found to be more prevalent among male students. Most of the victims of stalking knew their stalkers, while the offender in general violence was typically a stranger. Stalking victimization often included violence and continued for a lengthy period. The victim-stalking relationship and stalking behaviors were found to be associated with stalking violence and stalking duration. Based on three identified stalking dimensions (violence, surveillance, contact seeking), the present study found five distinct victim subgroups (classes). Along with the victim-stalker relationship, the victim subgroups emerged as important factors contributing to the stalking duration. Victims of violent stalking did not differ greatly from victims of non-violent stalking in their use of behavioral coping tactics, while exposure to violent stalking had an effect on the use of coping strategies. The victim-offender relationship was also associated to a set of symptoms regarding violence victimization. Furthermore, violence victimization had a significant main effect on specific symptoms (mental health symptoms, alcohol consumption, symptom index), while gender had a significant main effect on most symptoms, yet no interaction effect was found. The present results also show that victims of violence are overrepresented among frequent health care users. The present findings add to the literature on the prevalence and nature of stalking and violence victimization among Finnish university students. Moreover, the present findings stress the importance of violence prevention and intervention in student health care, and may be used as a guideline for policy makers, as well as health care and law enforcement professionals dealing with youth violence prevention.

Memory disorders in acute encephalitis : A neuropsychological study

Acute encephalitis is an inflammation of the brain, mostly caused by viral infection. A variety of cognitive symptoms may persist after the acute stage, and neuropsychological assessment is crucial in evaluation of the outcome. The most commonly reported sequelae are memory deficits. The main aims of this study were to investigate the types of memory impairment in various encephalitides, the frequency of global amnesia following encephalitis, and the changes in the deficits during follow-up. Between 1 January 1985 and 31 December 1994, 77 adult patients under the age of 75 with acute encephalitis but without alcohol abuse, or coexisting or previous neurological diseases were consecutively referred for neuropsychological examination at the Department of Neurology, Helsinki University Central Hospital. The aetiology was established in 44/77 (57%) patients; 17 had Herpes simplex virus encephalitis (HSVE). Transient amnesia (TENA) at the acute stage of the disease was found in 70% of patients. Furthermore, similarly to brain trauma, TENA was found to indicate cognitive outcome. The frequency of persisting global amnesia syndrome with both anterograde and retrograde amnesia in all encephalitic patients was 6%. One patient had isolated retrograde amnesia, which is very rare. In HSVE the frequency of global amnesia was 12.5%, which is lower than expected. As a group, HSVE patients were not found to have a homogeneous pattern of amnesia, instead subgroups among all encephalitic patients were observed: some patients had impaired semantic memory, some had difficulty predominantly with executive functions and some suffered from an increased forgetting rate. Herpes zoster encephalitis was found to result in mild memory impairment only, and the qualitative features indicated a subcortical dysfunction. On the whole, the cognitive deficits were predominantly found to diminish during follow-up. Progressive deterioration was often associated with intractable epilepsy. The frequency of dementia was 12.5%. In conclusion, the neuropsychological outcome, especially in HSVE, was more favourable than has previously been reported, possibly due to early acyclovir medication. Memory disorders after encephalitis should not be considered uniform, and the need for neuropsychological rehabilitation should be considered case-by-case

Tieteellinen ajattelu yliopisto-opinnoissa : haastattelututkimus psykologian, teologian ja farmasian opiskelijoista

The aim of this dissertation is to explore the academic thinking and personal epistemology of university students. More specifically, the aim is to understand and promote students’ research and academic skills as a central goal of academic studies in the research-intensive university of Helsinki. Two of the four studies examine the personal epistemology of psychology students in different study phases, and the variation in personal epistemology among final-year psychology, theology and pharmacy students. Furthermore, personal epistemology was explored as a phenomenon among the student groups. In the fourth study the individual answers of the students interviewed are investigated in more detail. The main focus is on examining students’ beliefs about the nature of knowledge and knowledge acquisition as a representation of their personal epistemology. Study I presents a model which describes the main elements and aspects of teaching and learning in pharmacy education. Firstly, the meaning of quality of teaching and learning is explored. On the basis of this information, the study concentrates on the pedagogical implications of changing pharmacy teaching to improve the quality of learning. Study II describes the results of a cross-sectional study of psychology students participating in undergraduate and master’s level psychology programmes. The students (N = 53) were interviewed concerning their beliefs about knowledge and knowing, the aim being to explore students’ responses about thinking and reasoning. The results are analysed using content analysis to create categories of personal epistemology and comparisons among the students according to the phase of their studies. Study III examines interdisciplinary differences in final-year psychology, pharmacy and theology students’ (N = 52) academic thinking and personal epistemology. The aims of study IV are to examine and compare the consistency of personal epistemology profiles among university students (N = 87) representing three academic disciplines. The individual answers are examined and rated on a scale from absolutist to evaluativist thinking. On the basis of this data, three personal epistemology profiles are identified: a) absolutist profiles; b) relativistic profiles; and c) evaluativist profiles consisting of the subgroups entitled “limited” and “sophisticated”. The results of the studies clearly demonstrate that personal epistemology varies between students in different age groups, study phases, and disciplines. Three categories, including several subcategories, emerge to describe the personal epistemology of students. Furthermore, three personal epistemology profiles can be identified from the data. The comparison between students reveals interesting differences and similarities among student groups, and developmental trends of personal epistemology.

I konstens namn - scenen som arbetsmiljö : Arbetsplatsmobbning ur skådespelarperspektiv

Workplace bullying is a topic of current interest in Finland. Workplace bullying is found in all professions, including the artistic ones. This thesis aims to explore workplace bullying from the view of the Finland-Swedish actors as a phenomenon that within dramatic art is difficult to define due to the fact that the body and emotions of an actor constitute his or her working tools. The research aims to deepen the understanding of the actors’ working situation, and particularly of the difficulties and problems actors face when exercising their job. The research problems are: What forms of bullying are the actors exposed to? Who is bullying? How is the bullying received by the actors, and what are the possible consequences? The theoretical orientation of this thesis is based upon dialogical philosophy where phenomenology, hermeneutics and dialog meet in an orientation where the unseen is emphasized and made visible. Artistic leadership should be based upon a pedagogic understanding that by an open and equal dialog with the Other recognizes human diversity. The narrative research was undertaken by using an interview guide for the interviews with eleven actors, six women and five men with the voice of a sixth man represented by an article. The interviews, each on average 118 minutes, were recorded and transcribed. The method of discursive analysis was initiated by numerous reflective readings based on analytic induction. The inductive part of the analysis consisted of mapping out the individual experiences of bullying where after the process of finding connecting common features in the extensive material took place. The coded data was then deductively grouped together according to the research problems, and subgroups were formed for deeper description. The research findings show that workplace bullying is an everyday occurrence within the field of dramatic art. Actors are bullied by theatre managers and directors as well as by colleagues and other personnel. The main areas of bullying is depreciation of one’s professional skills, the existing jargon, sexual harassment, collective bullying and bullying because of personal qualities. A significant finding concerning this problem was the existing culture of silence. Even if actually seeing and hearing a colleague being bullied, few stood up to defend the person being bullied because of fear of retaliation. Even the person actually being the object for bullying found it difficult to take any actions.

Semanttisen webin ontologisen tekstiilikäsitteistön kehittäminen ja liittäminen museoiden luettelointitietoihin

DEVELOPING A TEXTILE ONTOLOGY FOR THE SEMANTIC WEB AND CONNECTING IT TO MUSEUM CATALOGING DATA The goal of the Semantic Web is to share concept-based information in a versatile way on the Internet. This is achievable using formal data structures called ontologies. The goal of this re-search is to increase the usability of museum cataloging data in information retrieval. The work is interdisciplinary, involving craft science, terminology science, computer science, and museology. In the first part of the dissertation an ontology of concepts of textiles, garments, and accessories is developed for museum cataloging work. The ontology work was done with the help of thesauri, vocabularies, research reports, and standards. The basis of the ontology development was the Museoalan asiasanasto MASA, a thesaurus for museum cataloging work which has been enriched by other vocabularies. Concepts and terms concerning the research object, as well as the material names of textiles, costumes, and accessories, were focused on. The research method was terminological concept analysis complemented by an ontological view of the Semantic Web. The concept structure was based on the hierarchical generic relation. Attention was also paid to other relations between terms and concepts, and between concepts themselves. Altogether 977 concept classes were created. Issues including how to choose and name concepts for the ontology hierarchy and how deep and broad the hierarchy could be are discussed from the viewpoint of the ontology developer and museum cataloger. The second part of the dissertation analyzes why some of the cataloged terms did not match with the developed textile ontology. This problem is significant because it prevents automatic ontological content integration of the cataloged data on the Semantic Web. The research datasets, i.e. the cataloged museum data on textile collections, came from three museums: Espoo City Museum, Lahti City Museum and The National Museum of Finland. The data included 1803 textile, costume, and accessory objects. Unmatched object and textile material names were analyzed. In the case of the object names six categories (475 cases), and of the material names eight categories (423 cases), were found where automatic annotation was not possible. The most common explanation was that the cataloged field was filled with a long sentence comprised of many terms. Sometimes in the compound term, the object name and material, or the name and the way of usage, were combined. As well, numeric values in the material name cataloging field prevented annotation and so did the absence of a corresponding concept in the ontology. Ready-made drop-down lists of materials used in one cataloging system facilitated the annotation. In the case of naming objects and materials, one should use terms in basic form without attributes. The developed textile ontology has been applied in two cultural portals, MuseumFinland and Culturesampo, where one can search for and browse information based on cataloged data using integrated ontologies in an interoperable way. The textile ontology is also part of the national FinnONTO ontology infrastructure. Keywords: annotation, concept, concept analysis, cataloging, museum collection, ontology, Semantic Web, textile collection, textile material

Teologian opiskelijoiden henkilökohtaiset projektit ja opintomenestys

Motivation and personal goals play an important role in the ways in which people direct their behavior. Personal goals are closely connected with well-being but they also relate to how people perform in different achievement domains. Many studies show that evaluating study-related goals as important, easy to attain and non stressful, predict better academic achievements than evaluating them as non attainable and stressful (Salmela-Aro & Nurmi, 1997b). The aim of this study was to describe motivational factors among theology students. They form an interesting group in terms of exploring connections between motivation, spiritual goals and academic achievements. The average duration of graduation at the Faculty of Theology is among the highest at the University of Helsinki. On the other hand, it may be assumed that many theology students have spiritual goals which affect their studies. A special focus was paid on the different evaluations of study-related personal projects and how they are related to academic achievement. A methodology of personal projects (Little, 1983) was used to study what kind of personal goals theology students are engaged in during their studies. In the first part of the questionnaire the subjects (N=133) were asked to describe important personal projects. They were given four numbered lines for their written responses. In the second part the subjects were asked to rate projects concerning their studies according to 13 dimensions using a 7-point Likert-scale. Three subgroups were formed on a K-Means Cluster Analysis on the basis of evaluations of the study-related projects. The groups were named committed, self-fulfillers and non-committed according to their evaluations of their study related projects. Academic achievements among the different groups varied substantially. After two years of studying the students who were in the committed group had completed on an average twenty study credits more than those who were in the non-committed group. Self-fulfillers placed in the middle of the three groups. Committed and self-fulfiller students also reported higher levels of intrinsic reasons for striving towards study-related goals. The results indicate that goals reported at the beginning of studies predicted academic achievement later on. The results also showed that different evaluations of goals have long lasting connections to progress in studying. Implications for student well-being and how these results can be utilized for student counseling are discussed.

Candidate gene studies on cardiovascular traits

Cardiovascular diseases (CVD) are a major cause of death and disability in Western countries and a growing health problem in the developing world. The genetic component of both coronary heart disease (CHD) and ischemic stroke events has been established in twin studies, and the traits predisposing to CVD, such as hypertension, dyslipidemias, obesity, diabetes, and smoking behavior, are all partly hereditary. Better understanding of the pathophysiology of CVD-related traits could help to target disease prevention and clinical treatment to individuals at an especially high disease risk and provide novel pharmaceutical interventions. This thesis aimed to clarify the genetic background of CVD at a population level using large Nordic population cohorts and a candidate gene approach. The first study concentrated on the allelic diversity of the thrombomodulin (THBD) gene in two Finnish cohorts, FINRISK-92 and FINRISK-97. The results from this study implied that THBD variants do not substantially contribute to CVD risk. In the second study, three other candidate genes were added to the analyses. The study investigated the epistatic effects of coagulation factor V (F5), intercellular adhesion molecule -1 (ICAM1), protein C (PROC), and THBD in the same FINRISK cohorts. The results were encouraging; we were able to identify several single SNPs and SNP combinations associating with CVD and mortality. Interestingly, THBD variants appeared in the associating SNP combinations despite the negative results from Study I, suggesting that THBD contributes to CVD through gene-gene interactions. In the third study, upstream transcription factor -1 (USF1) was analyzed in a cohort of Swedish men. USF1 was associated with metabolic syndrome, characterized by accumulation of different CVD risk factors. A putative protective and a putative risk variant were identified. A direct association with CVD was not observed. The longitudinal nature of the study also clarified the effect of USF1 variants on CVD risk factors followed in four examinations throughout adulthood. The three studies provided valuable information on the study of complex traits, highlighting the use of large study samples, the importance of replication, and the full coverage of the major allelic variants of the target genes to assure reliable findings. Although the genetic basis of coronary heart disease and ischemic stroke remains unknown, single genetic findings may facilitate the recognition of high-risk subgroups.

Microarrays in molecular profiling of cancer - focus on head and neck squamous cell carcinoma

Microarrays have a wide range of applications in the biomedical field. From the beginning, arrays have mostly been utilized in cancer research, including classification of tumors into different subgroups and identification of clinical associations. In the microarray format, a collection of small features, such as different oligonucleotides, is attached to a solid support. The advantage of microarray technology is the ability to simultaneously measure changes in the levels of multiple biomolecules. Because many diseases, including cancer, are complex, involving an interplay between various genes and environmental factors, the detection of only a single marker molecule is usually insufficient for determining disease status. Thus, a technique that simultaneously collects information on multiple molecules allows better insights into a complex disease. Since microarrays can be custom-manufactured or obtained from a number of commercial providers, understanding data quality and comparability between different platforms is important to enable the use of the technology to areas beyond basic research. When standardized, integrated array data could ultimately help to offer a complete profile of the disease, illuminating mechanisms and genes behind disorders as well as facilitating disease diagnostics. In the first part of this work, we aimed to elucidate the comparability of gene expression measurements from different oligonucleotide and cDNA microarray platforms. We compared three different gene expression microarrays; one was a commercial oligonucleotide microarray and the others commercial and custom-made cDNA microarrays. The filtered gene expression data from the commercial platforms correlated better across experiments (r=0.78-0.86) than the expression data between the custom-made and either of the two commercial platforms (r=0.62-0.76). Although the results from different platforms correlated reasonably well, combining and comparing the measurements were not straightforward. The clone errors on the custom-made array and annotation and technical differences between the platforms introduced variability in the data. In conclusion, the different gene expression microarray platforms provided results sufficiently concordant for the research setting, but the variability represents a challenge for developing diagnostic applications for the microarrays. In the second part of the work, we performed an integrated high-resolution microarray analysis of gene copy number and expression in 38 laryngeal and oral tongue squamous cell carcinoma cell lines and primary tumors. Our aim was to pinpoint genes for which expression was impacted by changes in copy number. The data revealed that especially amplifications had a clear impact on gene expression. Across the genome, 14-32% of genes in the highly amplified regions (copy number ratio >2.5) had associated overexpression. The impact of decreased copy number on gene underexpression was less clear. Using statistical analysis across the samples, we systematically identified hundreds of genes for which an increased copy number was associated with increased expression. For example, our data implied that FADD and PPFIA1 were frequently overexpressed at the 11q13 amplicon in HNSCC. The 11q13 amplicon, including known oncogenes such as CCND1 and CTTN, is well-characterized in different type of cancers, but the roles of FADD and PPFIA1 remain obscure. Taken together, the integrated microarray analysis revealed a number of known as well as novel target genes in altered regions in HNSCC. The identified genes provide a basis for functional validation and may eventually lead to the identification of novel candidates for targeted therapy in HNSCC.

Evidence-based perspective on CP rehabilitation : Reviews on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices

This thesis utilises an evidence-based approach to critically evaluate and summarize effectiveness research on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices in children and adolescents with cerebral palsy (CP). It aims to assess the methodological challenges of the systematic reviews and trials, to evaluate the effectiveness of interventions in current use, and to make suggestions for future trials Methods: Systematic reviews were searched from computerized bibliographic databases up to August 2007 for physiotherapy and physiotherapy-related interventions, and up to May 2003 for orthotic devices. Two reviewers independently identified, selected, and assessed the quality of the reviews using the Overview Quality Assessment Questionnaire complemented with decision rules. From a sample of 14 randomized controlled trials (RCT) published between January 1990 and June 2003 we analysed the methods of sampling, recruitment, and comparability of groups; defined the components of a complex intervention; identified outcome measures based on the International Classification of Functioning, Disability and Health (ICF); analysed the clinical interpretation of score changes; and analysed trial reporting using a modified 33-item CONSORT (Consolidated Standards of Reporting Trials) checklist. The effectiveness of physiotherapy and physiotherapy-related interventions in children with diagnosed CP was evaluated in a systematic review of randomised controlled trials that were searched from computerized databases from January 1990 up to February 2007. Two reviewers independently assessed the methodological quality, extracted the data, classified the outcomes using the ICF, and considered the level of evidence according to van Tulder et al. (2003). Results: We identified 21 reviews on physiotherapy and physiotherapy-related interventions and five on orthotic devices. These reviews summarized 23 or 5 randomised controlled trials and 104 or 27 observational studies, respectively. Only six reviews were of high quality. These found some evidence supporting strength training, constraint-induced movement therapy or hippotherapy, and insufficient evidence on comprehensive interventions. Based on the original studies included in the reviews on orthotic devices we found some short-term effects of lower limb casting on passive range of movement, and of ankle-foot orthoses on equinus walk. Long term effects of lower limb orthoses have not been studied. Evidence of upper limb casting or orthoses is conflicting. In the sample of 14 RCTs, most trials used simple randomisation, complemented with matching or stratification, but only three specified the concealed allocation. Numerous studies provided sufficient details on the components of a complex intervention, but the overlap of outcome measures across studies was poor and the clinical interpretation of observed score changes was mostly missing. Almost half (48%) of the applicable CONSORT-based items (range 28 32) were reported adequately. Most reporting inadequacies were in outcome measures, sample size determination, details of the sequence generation, allocation concealment and implementation of the randomization, success of assessor blinding, recruitment and follow-up dates, intention-to-treat analysis, precision of the effect size, co-interventions, and adverse events. The systematic review identified 22 trials on eight intervention categories. Four trials were of high quality. Moderate evidence of effectiveness was established for upper extremity treatments on attained goals, active supination and developmental status, and of constraint-induced therapy on the amount and quality of hand use and new emerging behaviours. Moderate evidence of ineffectiveness was found for strength training's effect on walking speed and stride length. Conflicting evidence was found for strength training's effect on gross motor function. For the other intervention categories the evidence was limited due to the low methodological quality and the statistically insignificant results of the studies. Conclusions: The high-quality reviews provide both supportive and insufficient evidence on some physiotherapy interventions. The poor quality of most reviews calls for caution, although most reviews drew no conclusions on effectiveness due to the poor quality of the primary studies. A considerable number of RCTs of good to fair methodological and reporting quality indicate that informative and well-reported RCTs on complex interventions in children and adolescents with CP are feasible. Nevertheless, methodological improvement is needed in certain areas of the trial design and performance, and the trial authors are encouraged to follow the CONSORT criteria. Based on RCTs we established moderate evidence for some effectiveness of upper extremity training. Due to limitations in methodological quality and variations in population, interventions and outcomes, mostly limited evidence on the effectiveness of most physiotherapy interventions is available to guide clinical practice. Well-designed trials are needed, especially for focused physiotherapy interventions.

Routine Measurement of Health-Related Quality of Life in Assessing Cost-Effectiveness in Secondary Health Care

Aims: The aims of this study were 1) to identify and describe health economic studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL); 2) to test the feasibility of routine collection of health-related quality of life (HRQoL) data as an indicator of effectiveness of secondary health care; and 3) to establish and compare the cost-utility of three large-volume surgical procedures in a real-world setting in the Helsinki University Central Hospital, a large referral hospital providing secondary and tertiary health-care services for a population of approximately 1.4 million. Patients and methods: So as to identify studies that have used QALYs as an outcome measure, a systematic search of the literature was performed using the Medline, Embase, CINAHL, SCI and Cochrane Library electronic databases. Initial screening of the identified articles involved two reviewers independently reading the abstracts; the full-text articles were also evaluated independently by two reviewers, with a third reviewer used in cases where the two reviewers could not agree a consensus on which articles should be included. The feasibility of routinely evaluating the cost-effectiveness of secondary health care was tested by setting up a system for collecting HRQoL data on approximately 4 900 patients' HRQoL before and after operative treatments performed in the hospital. The HRQoL data used as an indicator of treatment effectiveness was combined with diagnostic and financial indicators routinely collected in the hospital. To compare the cost-effectiveness of three surgical interventions, 712 patients admitted for routine operative treatment completed the 15D HRQoL questionnaire before and also 3-12 months after the operation. QALYs were calculated using the obtained utility data and expected remaining life years of the patients. Direct hospital costs were obtained from the clinical patient administration database of the hospital and a cost-utility analysis was performed from the perspective of the provider of secondary health care services. Main results: The systematic review (Study I) showed that although QALYs gained are considered an important measure of the effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited. Of the reviewed full-text articles, only 70 reported QALYs based on actual before after measurements using a valid HRQoL instrument. Collection of simple cost-effectiveness data in secondary health care is feasible and could easily be expanded and performed on a routine basis (Study II). It allows meaningful comparisons between various treatments and provides a means for allocating limited health care resources. The cost per QALY gained was 2 770 for cervical operations and 1 740 for lumbar operations. In cases where surgery was delayed the cost per QALY was doubled (Study III). The cost per QALY ranges between subgroups in cataract surgery (Study IV). The cost per QALY gained was 5 130 for patients having both eyes operated on and 8 210 for patients with only one eye operated on during the 6-month follow-up. In patients whose first eye had been operated on previous to the study period, the mean HRQoL deteriorated after surgery, thus precluding the establishment of the cost per QALY. In arthroplasty patients (Study V) the mean cost per QALY gained in a one-year period was 6 710 for primary hip replacement, 52 270 for revision hip replacement, and 14 000 for primary knee replacement. Conclusions: Although the importance of cost-utility analyses has during recent years been stressed, there are only a limited number of studies in which the evaluation is based on patients own assessment of the treatment effectiveness. Most of the cost-effectiveness and cost-utility analyses are based on modeling that employs expert opinion regarding the outcome of treatment, not on patient-derived assessments. Routine collection of effectiveness information from patients entering treatment in secondary health care turned out to be easy enough and did not, for instance, require additional personnel on the wards in which the study was executed. The mean patient response rate was more than 70 %, suggesting that patients were happy to participate and appreciated the fact that the hospital showed an interest in their well-being even after the actual treatment episode had ended. Spinal surgery leads to a statistically significant and clinically important improvement in HRQoL. The cost per QALY gained was reasonable, at less than half of that observed for instance for hip replacement surgery. However, prolonged waiting for an operation approximately doubled the cost per QALY gained from the surgical intervention. The mean utility gain following routine cataract surgery in a real world setting was relatively small and confined mostly to patients who had had both eyes operated on. The cost of cataract surgery per QALY gained was higher than previously reported and was associated with considerable degree of uncertainty. Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is two-fold compared to hip replacement. Cost-utility results from the three studied specialties showed that there is great variation in the cost-utility of surgical interventions performed in a real-world setting even when only common, widely accepted interventions are considered. However, the cost per QALY of all the studied interventions, except for revision hip arthroplasty, was well below 50 000, this figure being sometimes cited in the literature as a threshold level for the cost-effectiveness of an intervention. Based on the present study it may be concluded that routine evaluation of the cost-utility of secondary health care is feasible and produces information essential for a rational and balanced allocation of scarce health care resources.

Life events and social support among patients with major depressive disorder

The study is part of a research project of 269 psychiatric patients with major depression, Vantaa Depression Study, in the Department of Mental Health and Alcohol Research of the National Public Health Institute and the Department of Psychiatry of the Peijas Medical Care District. The aim was to study at the onset of MDE psychosocial differences in subgroups of patients and clustering of events into time before depression and its prodromal phase, to study whether more severe life events and less social support predict poorer outcome in all patients, but most among those currently in partial remission, whether social support declines as a consequence of time spent in MDE, is sensitive to improvement, and whether social support is influenced by neuroticism and extraversion. After screening, a semistructured interview (SCAN, version 2.0) was used for the presence of DSM-IV MDE, and other psychiatric diagnoses. Life events and social support were studied with semistructured methods (IRLE, Paykel 1983; IMSR, Brugha et al. 1987), perceived social support and neuroticism/extraversion with questionnaires (PSSS-R, Blumenthal et al. 1987; EPI, Eysenck and Eysenck 1964) at baseline, 6 and 18 months. At the onset of depression life events were common. No major differences between subgroups of patients were found; the younger had more events, whereas those with comorbid alcoholism and personality disorders perceived less support. Although events were distributed evenly between the time before depression, the prodromal phase and the index MDE, two thirds of the patients attributed their depression to some life event. Adversities and poor perceived support influenced the outcome of all psychiatric patients, most in the subgroup of full remission. In the partial remission group, the impact of severe events and in the MDE, perceived support was important. Low objective and subjective support were predicted by longer time spent in MDE. Along with improvement subjective support improved. Neuroticism and extraversion were associated with the size of social network and perceived support and predicted change of perceived support. In conclusion, adversities were common in all phases of depression. They may thus have many roles; before depression they may precipitate it, in the prodromal phase worsen symptoms, and during the MDE, the outcome of depression. Patients often attributed their depression to a life event. Psychosocial subgroup differences were quite small. Perceived support predicted the outcome of depression, and time spent in MDE objective and subjective support. Neuroticism and extraversion may modify the level and change particularly in perceived support, thereby indirectly effecting vulnerability to depression.

Human herpesvirus 6 in multiple sclerosis and encephalitis

Human herpesvirus 6 (HHV-6) was identified from patients with HIV and lymphoproliferative diseases in 1986. It is a β-herpesvirus and is divided into two subgroups, variants A and B. HHV-6 variant B is the cause of exanthema subitum, while variant A has not yet definitely proven to cause any disease. HHV-6, especially variant A, is a highly neurotropic virus and has been associated with many diseases of the central nervous system (CNS) such as encephalitis and multiple sclerosis (MS). The present studies were aimed to elucidate the role of HHV-6 and its two variants in neurological infections. Special attention was given to study the possible role of HHV-6 in the pathogenesis of MS. We studied the expression of HHV-6 antigens using immunohistochemistry in brain autopsy samples from patients with MS and controls. HHV-6 antigen was identified in 70% of MS specimens whereas 30% of control specimens expressed HHV-6 antigen. Serum and cerebrospinal fluid (CSF) samples were collected from patients with MS and patients with other neurological diseases (OND) from patients visiting Helsinki University Central Hospital Neurological Outpatient Clinic during the years 2003 and 2004. In addition, we studied 53 children with suspected encephalitis. We developed an immunofluorescence IgG-avidity assay for the detection of primary HHV-6A and HHV-6B infection. For HHV-6B antibodies, no differences were observed between patients with MS and OND. For HHV-6A both seroprevalence and mean titers were significantly higher in MS compared to OND. HHV-6A low-avidity IgG antibodies, suggestive of primary infection, were found in serum of two, three and one patient with definite MS, possible MS and OND, respectively. From pediatric patients with suspected encephalitis, six serum samples (11.3%) contained low-avidity antibodies, indicating a temporal association between HHV-6A infection and onset of encephalitis. Three out of 26 patients with CDMS and four out of 19 patients with CPMS had HHV-6 antibodies in their CSF compared to none of the patients with OND (p=0.06 and p=0.01, respectively). Two patients with CDMS and three patients with CPMS appeared to have specific intrathecal synthesis of HHV-6A antibodies. In addition, oligoclonal bands (OCB) were observed in the CSF of five out of nine MS patients tested, and in two the OCBs reacted specifically with HHV-6 antigen, which is a novel finding. These results indicate HHV-6 specific antibody production in the CNS and suggest that there is a subset of MS patients with an active or chronic HHV-6A infection in the CNS that might be involved in the pathogenesis of MS. Our studies suggest that HHV-6 is an important causative or associated virus in some neurological infections, such as encephalitis and it might contribute to the development of MS, at least in some cases. In conclusion, HHV-6 is a neurotropic virus that should be taken into consideration when studying acute and chronic CNS diseases of unknown origin.