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1.
  • Johansson, Inger (författare)
  • Quality of care and assessment of health among elderly in actue care.
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis describes nursing staff's opinion of quality of care and work satisfaction and elderly patients' perception of health, functional capacity, quality of life and sense of coherence (SOC) from a prognostic point of view. The research was performed within several surgical and orthopaedic wards, and different instruments were developed and tested for reliability and validity. The study groups consisted of nursing staff (n=66), surgical patients clinically ready for discharge (n=53) and a consecutive sample of patients with hip fracture (n=73). All patients were 60+ years of age and livin  in their own homes before their stay in hospital.The nursing staff answered questionnaires concerning work satisfaction and perceived quality of care before and one year after the introduction of modular nursing. Among the respondents considerable differences were noted in one ward one year after the intervention, particularly concerning their relationship with colleagues, identification and connnitment, and quality of care. Key factors for this outcome could be related to the quality of the interpersonal relationships and the leadership of the ward.Significant differences between subgroups were revealed when using a Swedish version of the Health Assessment Form (HAF) and a tool measuring Sense of Coherence (SOC) in personal interviews among elderly patients clinically ready for discharge. The patients who could return home showed less discomfort concerning physical variables such as breathing and elimination of urine and scored higher within emotional status and SOC than those who were referred to an institution or were deceased before the one month follow-up. The result indicated that the HAF as well as SOC had some prognostic value for further care as well as for survival/fatal outcome for patients clinically ready for discharge.The Swedish version of the NEECHAM Confusion Scale was found to be reliable and valid for detecting and following up acute confusional states among patients with hip fracture. The part of the scale measuring vital function was found to have predictive power in relation to the Quality of Life Index (QLI) at the four-month follow-up. The parts reflecting cognitive function and urinary continence predicted significantly for function of daily living activities (I-ADL), measured with the Standardized Practical Equipment (SPE). Patients with a stronger SOC, compared with those with a weaker, were discharged earlier from the hospital, reported a higher score on the QLI and performed I-ADL better four months after discharge from the hospital.The findings highlight the importance of having a broad range of valid and reliable instruments when following up organisational changes among nursing staff as well as for assessing the health and functional needs of elderly patients in acute care in order to predict future developments.
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2.
  • Zimdahl, Anna, 1987- (författare)
  • Pharmacogenetic studies of thiopurine methyltransferase genotype-phenotype concordance and effect of methotrexate on thiopurine metabolism
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The thiopurines (6-mercaptopurine [6-MP], 6-thioguanine and azathioprine) are cytotoxic drugs used in the treatment of acute lymphoblastic leukemia (ALL), inflammatory bowel diseases, certain autoimmune diseases and after transplantation. The metabolism of thiopurines is complex with several enzymes involved in the conversion into active drug metabolites. One of the enzymes, thiopurine methyltransferase (TPMT), is one of the best examples of implemented pharmacogenetics so far. Due to lowered TPMT enzyme activity caused by genetic polymorphism, carriers of heterozygous or homozygous defective TPMT alleles need dose reduction to avoid cytotoxic adverse reactions like myelosuppression or hepatotoxicity if treated with thiopurines.To determine TPMT status before the start of treatment, genotyping (for the three most occurring TPMT alleles) and/or phenotyping (TPMT enzyme activity measurements) are used in the clinical setting. In the focus of this thesis, concordance of these methods was investigated in a large cohort of unique samples (n=12,663) collected in the routine analysis service of TPMT status determinations in Linköping. By sequencing all exons in samples where the results of the two methods differed, rare or novel TPMT alleles were discovered. Four TPMT alleles (TPMT*41, *42, *43, *44), not previously described, were characterized in terms of clinical in vivo data as well as protein structure and stability data obtained from recombinant human TPMT (rTPMT) produced by E. Coli and biophysical methods.The clinical cohort was also used in the search for other factors (except genetic factors) that influence TPMT enzyme activity, and both age and gender turned out to affect TPMT enzyme activity level. In addition, TPMT enzyme activity in the early treatment of ALL was investigated and shown to be significantly lower at time of ALL diagnosis.In the treatment protocol of ALL, the combined treatment using 6-MP and methotrexate (MTX) has increased the positive outcomes since the start in the 1950s. Despite this, the synergistic effect of these drugs is not yet fully understood. To evaluate the effect of MTX on thiopurine metabolism specifically, TPMT enzyme activity, TPMT gene expression, and thiopurine metabolite levels were determined before and after MTX infusions in vivo and after cotreatment in lymphoblasts in vitro. In the presence of MTX, TPMT enzyme activity and metabolite levels decreased, both in vivo and in vitro, although dose- and time-dependent. In addition, MTX bound to rTPMT and caused inhibition of rTPMT enzyme activity.The results found in the scope of this thesis may be used for further individualization of thiopurine treatment.
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