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Coming dissertations at MedFak

  • Physical activity and exercise during curative oncological treatment : exploring the effects of exercise intensity and behaviour change support, safety, and patients’ and exercise professionals’ experiences Author: Anna Henriksson Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-406981 Publication date: 2020-04-22 13:19

    Aims: This thesis aimed to explore the effects of exercise intensity and behaviour change support (BCS), the safety of exercise, and experiences of exercise for both patients and exercise professionals during oncological treatment (e.g. neo/adjuvant chemotherapy, endocrine treatment, radiotherapy). This thesis is based on data from the Phys-Can (Physical training and Cancer) multicentre research program, consisting of a feasibility study, an observation study, and a randomised controlled trial (RCT). Methods: Paper I and II were quantitative studies. Paper I was a RCT with a 2x2 factorial design. Patients newly diagnosed with breast, prostate, or colorectal cancer about to start oncological treatment were randomised to six months of high intensity (HI) or low-moderate intensity (LMI) supervised group based resistance- and home-based endurance training, with or without additional BCS. The primary outcome, cancer related fatigue (CRF), was assessed by the Multidimensional Fatigue Inventory. Multiple linear regression and additional responder analysis for primary outcomes were performed. Paper II was a descriptive and comparative study based on secondary data from the observation study and RCT. Data were presented descriptively, and related factors to adverse events (AEs) were analysed with logistic regressions. Paper III and IV were qualitative studies. Participants were patients with breast, prostate, or colorectal cancer undergoing oncological treatment (Paper III) or coaches supervising exercise for participants in the RCT (Paper IV). Data were collected through semi-structured individual- (Paper III and IV) and focus group interviews (Paper III) and analysed with qualitative content analysis (Paper III) and thematic analysis (Paper IV). Main results and conclusions: The results from this thesis indicate that exercise at HI may not improve CRF in comparison with exercise at LMI in patients undergoing treatment, thus patients can be advised to exercise at either preferred intensity. Also, additional BCS did not improve CRF in relatively motivated patients receiving supervised exercise (Paper I). Furthermore, exercise-related AEs in persons undergoing oncological treatment are minor, of musculoskeletal origin, and with a similar incidence as in healthy populations. However, a higher risk of minor exercise-related AEs was reported in HI groups than in LMI groups. More serious AEs were rare, thus it seems safe to exercise even at HI for these patient groups (Paper II). The results also indicated that patients could experience side effects and concerns regarding the safety of exercising during oncological treatment as barriers to engage in physical activity. Therefore, engaging in physical activity before the onset of side effects from treatment and providing information regarding physical activity to patients could be beneficial (Paper III). Professionals supervising exercise for patients may find it highly rewarding, which is promising for implementation in cancer rehabilitation. However, patients may still receive contradictory information regarding the safety of exercise from health care staff, which can be difficult for exercise professionals to counteract (Paper IV).

  • Forecasting myocardial infarction and subsequent behavioural outcomes Author: John Wallert Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-407334 Publication date: 2020-04-22 11:44

    This thesis is compiled from four studies dealing with the prediction of myocardial infarction (MI) and some associated risk behaviours post MI.

    Study 1 extends the field of possible psychosocial stress-triggering of MI to Sweden, and to the phenomenon of temporal crests and troughs in national MI rates. These findings are in the present thesis integrated into a more comprehensive theoretical framework than provided by previous studies. By controlling for different confounders, analysis in subgroups, and more, the probable effect of psychosocial stress on the triggering of MI producing slight oscillations in daily MI rates at different temporal cycles was supported.

    Study 2 extends the existing literature of cognitive epidemiology to secondary preventive cardiology. Males with higher cognitive ability (CA), as assessed at mandatory military conscription in young adulthood, were found to be more adherent to their statin medication post MI, approximately 30 years later. The association is likely causal, given the fundamental importance of CA as a predictor for our individual ability to understand, plan, and execute everyday behaviour, including such health promoting behaviour as adhering to statin medication after MI.

    Study 3 continues the thesis thread of predicting clinically relevant health-promoting behaviour. It generated important hypotheses of what predicts adherence to internet-based cognitive behaviour therapy (ICBT) for symptoms of anxiety and/or depression after MI. In particular, the linguistic variables which were derived from what the patients actually wrote online to their ICBT therapist, predicted adherence. Using a flexible random forest model with a moderately sized sample, the aim was to handle a range of predictors and possible higher order effects in the relative strength estimation of these predictors.

    Study 4 presents the derivation and external validation of a new risk model, STOPSMOKE. Developed as a linear support vector machine with robust resampling, STOPSMOKE proved accurate in the unseen validation cohort for predicting one-year smoking abstinence at the start of cardiac rehabilitation (CR) post MI. STOPSMOKE predictions may inform the targeting of more elaborate interventions to high risk patients. Today, such intervention is not systematic as standard counselling does not account for the individual probability of future smoking abstinence failure. STOPSMOKE thus provides a novel real-world probabilistic basis for the risk of future smoking abstinence failure after MI. This basis may then be used by clinicians, patients, and organisations to tailor smoking intervention as best suited the particular individual or high-risk group. Implemented as part of a spectrum of models in a semi-automatic system, cost-effective tailored risk assessment could allow for augmented CR for future patients.

  • Lupus Nephritis – Genetic Impact on Clinical Phenotypes, Disease Severity and Renal Outcome Author: Karin Bolin Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-401809 Publication date: 2020-04-22 10:44

    Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that can affect every organ system. Lupus nephritis (LN) is one of the more serious SLE manifestations. Whilst the genetic background of SLE has been thoroughly investigated, less is known about the background of LN. The aim of this thesis was to further elucidate the genetic background of LN, its subtypes and outcome.

    In paper I, we analysed genetic variations for association with LN, its severe form proliferative nephritis and renal outcome, in two SLE cohorts. Patients and controls were genotyped and association analyses were performed for patients versus controls and for patients with or without a specific clinical manifestation. In the case-control analysis of cohort I, four highly linked risk alleles in the STAT4 gene were associated with LN with genome-wide significance. In the case-only meta-analysis of the two cohorts, a STAT4 risk allele was associated with severe renal insufficiency. We conclude that genetic variations in STAT4 predispose to LN and a worse outcome with severe renal insufficiency.

    In paper II, we describe a case of severe SLE on the basis of C1q deficiency. By sequencing, a mutation in the C1qC gene leading to a premature stop codon was found. The patient was also found to carry risk alleles in several SLE-associated variants. Interferon alpha (IFN-α) levels were analysed over time in patient serum, and were found to correlate with disease activity. The patient’s serum had a strong interferogenic capacity when stimulating peripheral blood mononuclear cells from healthy individuals. With this study, we further emphasise the role of IFN-α in C1q deficiency and highlight the need to consider inherited impairments in the complement system in SLE with childhood onset.

    In paper III, we studied the impact of sex on disease manifestations in SLE. Female SLE patients more often presented with malar rash, photosensitivity, oral ulcers and arthritis, whilst the frequency of serositis, renal disorder and immunologic disorder were higher among male patients. Women were younger at LN onset, whereas men had a higher risk for progression into end-stage renal disease.

    In paper IV, we analysed genetic variations for association with LN and its subtypes in three SLE cohorts. Patients were genotyped and association analyses were performed for patients with versus without different phenotypes. We found genetic variations in the BANK1 gene to be associated with LN.

    In conclusion, this thesis provides further insight into the genetic background of renal manifestations in patients with SLE.

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