Autologous Stem Cell Transplantation In Multiple Myeloma

Background. Multiple myeloma (MM) is the second most common hematologic malignancy after lymphomas In Finland: the annual incidence of MM is approximately 200. For three decades the median survival remained at 3 to 4 years from diagnosis until high-dose melphalan treatment supported by autologous stem cell transplantation (ASCT) became the standard of care for newly diagnosed MM since the mid 1990’s and the median survival increased to 5 – 6 years. This study focuses on three important aspects of ASCT, namely 1) stem cell mobilization, 2) single vs. double ASCT as initial treatment, and 3) the role of minimal residual disease (MRD) for longterm outcome. Aim. The aim of this series of studies was to evaluate the outcomes of MM patients and the ASCT procedure at the Turku University Central Hospital, Finland. First, we tried to identify which factors predict unsuccessful mobilization of autologous stem cells. Second, we compared the use of short-acting granulocyte-colony stimulating factor (GCSF) with long-acting G-CSF as mobilization agents. Third, one and two successive ASCTs were compared in 100 patients with MM. Fourth, for patients in complete response (CR) after stem cell transplantation (SCT), patient-specific probes for quantitative allele-specific oligonucleotide polymerase-chain reaction (qASO-PCR) measurements were designed to evaluate MRD and its importance for long-term outcome. Results. The quantity of previous chemotherapy and previous interferon use were significant pre-mobilization factors that predicted mobilization failure, together with some factors related to mobilization therapy itself, such as duration and degree of cytopenias and occurrence of sepsis. Short-acting and long-acting G-CSF combined with chemotherapy were comparable as stem cells mobilizers. The progression free (PFS) and overall survival (OS) tended to be longer after double ASCT than after single ASCT with a median follow-up time of 4 years, but this difference disappeared as the follow-up time increased. qASO-PCR was a good and sensitive divider of the CR patients into two prognostic groups: MRD low/negative (≤ 0.01%) and MRD high (>0.01%) groups with a significant difference in PFS and suggestively also in OS. Conclusions. When the factors prediciting a poor outcome of stem cell mobilization prevail, it is possible to identify those patients who need specific efforts to maximize the mobilization efficacy. Long-acting pegfilgrastim is a practical and effective alternative to short-acting filgrastim for mobilization therapy. There is no need to perform double ASCT on all eligible patients. MRD assessment with qASO-PCR is a sensitive method for evaluation of the depth of the CR response and can be used to predict long-term outcome after ACST.

Assessment of total cardiovascular risk in hypertensive subjects

Valtimotautiriskin arviointi verenpainepotilailla Valtimotaudit ovat yleisin kuolinsyy koko maailmassa. Väestön elintapojen muuttuminen ja ikääntyminen uhkaavat edelleen lisätä valtimotautien esiintyvyyttä. Kokemäenjokilaakson valtimotautien ehkäisyprojektin tavoitteena oli löytää 45–70-vuotiaasta väestöstä henkilöt, joilla on kohonnut riski sairastua valtimotauteihin. Kaksivaiheisen seulontamenetelmän avulla voitiin terveydenhoitajan antama elintapaneuvonta kohdistaa riskihenkilöihin ja rajoittaa lääkärin vastaanoton tarve niihin potilaisiin, jotka todennäköisesti hyötyvät ennaltaehkäisevästä lääkityksestä. Suomalainen tyypin 2 diabeteksen sairastumisriskin arviointikaavake ja hoitajan toteama kohonnut verenpaine osoittautuivat käytännöllisiksi menetelmiksi seuloa väestöstä riskihenkilöitä. Valtimotautien ehkäisyprojektissa Harjavallassa ja Kokemäellä todettiin verenpainetauti 1 106 henkilöllä, jotka eivät sairastaneet valtimotautia tai aiemmin todettua diabetesta. Heidän tutkimustulostensa avulla voidaan arvioida kohonneen verenpaineen vaikutusta sokeriaineenvaihduntaan ja verenpaineen aiheuttamiin kohde-elinvaurioihin. Sokeriaineenvaihdunnan häiriöt ovat verenpainetautia sairastavilla yleisempiä kuin väestössä muutoin. Käyttämällä metabolisen oireyhtymän kriteerejä sokerirasituskokeen suorittamisen edellytyksenä voidaan tutkimusten määrää vähentää kolmanneksella ja silti löytää lähes kaikki diabetesta tai sen esiastetta sairastavat verenpainepotilaat. Verenpainepotilaista etenkin metabolista oireyhtymää sairastavilla naisilla on suurentunut munuaisten vajaatoiminnan riski. Jos verenpainepotilaan munuaisten toimintaa arvioidaan pelkästään plasman kreatiniini -arvon perusteella, kolme neljästä munuaisten vajaatoimintaa potevasta jää toteamatta verrattuna laskennallisen glomerulusten suodattumisnopeuden määritykseen seulontamenetelmänä. Joka kolmannella verenpainetautia sairastavalla voidaan todeta alaraajavaltimoiden kovettumista; useammin niillä, joiden ylä- ja alaverenpaineen erotus, pulssipaine on yli 65 mmHg. Verenpainetauti on itsenäinen perifeerisen valtimotaudin vaaratekijä. Tutkimuksessa käytetty menetelmä nilkka-olkavarsipainesuhteen määrittämiseksi soveltunee hyvin perusterveydenhuollon käyttöön riskihenkilöiden löytämiseksi. Valtimotautien kokonaisriskin arviointimenetelmät tai uuden riskitekijän, herkän C-reaktiivisen proteiinin määritys eivät voi korvata kohde-elinvaurioiden mittaamista verenpainepotilaan valtimotautiriskin huolellisessa arvioinnissa.

Improving Quality of Life of Patients With Schizophrenia In Acute Psychiatric Wards

The overall goal of this study was to identify means by which the quality of life (QoL) of patients with schizophrenia could be improved in acute psychiatric wards. First, subjective QoL of patients (n=35) was explored. Second, two different QoL instruments (EuroQoL-5D, EQ-5D; Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, Q-LES-Q SF) were examined. Third, patients’ (n=35) and nurses’ (n=29) perceptions of nursing interventions to support patients’ QoL were examined. Fourth, the effect of three different patient education methods on patients’ QoL (n=311) was compared. The data were collected during the period 2005-2007. Patients named health, family, leisure activities, work or study, and social relationships most frequently as their important QoL areas. It emerged that patients’ QoL was impaired. Examination of two QoL instruments showed that the EQ-5D has moderate and the Q-LES-Q SF good internal consistency. Moreover, both instruments proved to be reasonably valid and feasible for use with patients with schizophrenia. Altogether six nursing interventions which nurses use to support patients’ QoL, and which should be further developed were identified from nurses’ descriptions: interventions related to care planning, empowering interventions, social interventions, activating interventions, security interventions, and interventions to support physical health. Evaluation of different patient education methods showed that patients’ QoL improved significantly during follow-up. No significant differences between groups were found. In light of the findings it is recommended to assess QoL of patients with schizophrenia as a basis for care planning and care evaluation in clinical settings. Valid and feasible instruments should be used in this assessment. Moreover, it is recommend that nursing interventions should be further developed to better improve patients’ QoL.

Induction practices : experiences of newly qualified teachers

The thesis consists of four studies (articles I–IV) and a comprehensive summary. The aim is to deepen understanding and knowledge of newly qualified teachers’ experiences of their induction practices. The research interest thus reflects the ambition to strengthen the research-based platform for support measures. The aim can be specified in the following four sub-areas: to scrutinise NQTs’ experiences of the profession in the transition from education to work (study I), to describe and analyse NQTs’ experiences of their first encounters with school and classroom (study II), to explore NQTs’ experiences of their relationships within the school community (study III), to view NQTs’ experiences of support through peer-group mentoring as part of the wider aim of collaboration and assessment (study IV). The overall theoretical perspective constitutes teachers’ professional development. Induction forms an essential part of this continuum and can primarily be seen as a socialisation process into the profession and the social working environment of schools, as a unique phase of teachers’ development contributing to certain experiences, and as a formal programme designed to support new teachers. These lines of research are initiated in the separate studies (I–IV) and deepened in the theoretical part of the comprehensive summary. In order to appropriately understand induction as a specific practice the lines of research are in the end united and discussed with help of practice theory. More precisely the theory of practice architectures, including semantic space, physical space-time and social space, are used. The methodological approach to integrating the four studies is above all represented by abduction and meta-synthesis. Data has been collected through a questionnaire survey, with mainly open-ended questions, and altogether ten focus group meetings with newly qualified primary school teachers in 2007–2008. The teachers (n=88 in questionnaire, n=17 in focus groups), had between one and three years of teaching experience. Qualitative content analysis and narrative analysis were used when analysing the data. What is then the collected picture of induction or the first years in the profession if scrutinising the results presented in the articles? Four dimensions seem especially to permeate the studies and emerge when they are put together. The first dimension, the relational ˗ emotional, captures the social nature of induction and teacher’s work and the emotional character intimately intertwined. The second dimension, the tensional ˗ mutable, illustrates the intense pace of induction, together with the diffuse and unclear character of a teacher’s job. The third dimension, the instructive ˗ developmental, depicts induction as a unique and intensive phase of learning, maturity and professional development. Finally, the fourth dimension, the reciprocal ˗ professional, stresses the importance of reciprocity and collaboration in induction, both formally and informally. The outlined four dimensions, or integration of results, describing induction from the experiences of new teachers, constitute part of a new synthesis, induction practice. This synthesis was generated from viewing the integrated results through the theoretical lens of practice architecture and the three spaces, semantic space, physical space-time and social space. In this way, a more comprehensive, refined and partially new architecture of teachers’ induction practices are presented and discussed.

Prenatal and perinatal risk factors for bipolar disorder

Bipolar disorder (BPD) is a severe mental disorder associated with considerable morbidity and mortality. Prenatal insults have been shown to be associated with later development of mental disorders and there is a growing interest in the potential role of prenatal and perinatal risk factors in the development of BPD. The aims of this thesis were to describe the overall study design of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B) and demographic characteristics of the sample. Furthermore, it was aimed to examine the association of parental age, parental age difference, perinatal complications and maternal smoking during pregnancy with BPD. This thesis is based on FIPS-B, a nested case-control study using several nationwide registers. The cases included all people born in Finland between January 1st 1983 and December 31st 1998 and diagnosed with BPD according to the Finnish Hospital Discharge Register (FHDR) before December 31st 2008. Controls for this study were people who were without BPD, schizophrenia or diagnoses related to these disorders, identified from the Population Register Centre (PRC), and matched two-fold to the cases on sex, date of birth (+/- 30 days), and residence in Finland on the first day of diagnosis of the matched case. Conditional logistic regression models were used to examine the association between risk factors and BPD. This study included 1887 BPD cases and 3774 matched controls. The mean age at diagnosis was 19.3 years and females accounted for 68% of the cases. Mothers with the lowest educational level had the highest odds of having BPD in offspring. Being born in Eastern and Southern region of Finland increased the odds of having BPD later in life. A U-shaped distribution of odds ratio was observed between paternal age and BPD in the unadjusted analysis. Maternal age and parental age difference was not associated with BPD. Birth by planned caesarean section was associated with increased odd of BPD. Smoking during pregnancy was not associated with BPD in the adjusted analyses. Region of birth and maternal educational level were associated with BPD. Both young and old father’s age was associated with BPD. Most perinatal complications and maternal smoking during pregnancy were not associated with BPD. The findings of this thesis, considered together with previous literature, suggest that the pre- and perinatal risk factor profile varies among different psychiatric disorders.