Coming theses from other universities
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Depression in teenagers and young adults : foundational studies of the new treatment paradigm TARA: Training for Awareness, Resilience, and Action
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222788
Introduction: Depression in adolescents and young adults is an increasing global health concern and available treatments are not convincingly effective. It is therefore important to develop and test novel treatments to improve treatment outcomes. This dissertation lays the foundation for the evaluation of a Swedish version of the treatment program Training for Awareness, Resilience, and Action (TARA), and tests the psychometric properties of the primary outcome measure for that evaluation.
Objectives: This dissertation aims to 1. Translate and pilot test TARA in Swedish medical students, 2. Evaluate the psychometric properties of the Swedish version of the Reynolds Adolescent Depression Scale second edition (RADS-2) in a clinical sample, 3. Perform a single arm multicenter clinical pilot study of the feasibility and safety of TARA and 4. Design a randomized controlled trial to test the clinical effectiveness of TARA.
Methods: The TARA manual was translated into Swedish and 23 self-selected medical students, with or without mental disorders, received TARA. Self-rating as well as qualitative evaluation was performed. Patients (N = 536 individuals) with a variety of psychiatric diagnoses completed RADS-2 and other questionnaires for psychometric evaluation of RADS- 2. Thirty-five adolescents and young adults with depression received TARA either face-to-face or online, with data collection before, during, and after the treatment. The study design and statistical analysis plan for the randomized controlled trial was conceived and developed.
Results: It was feasible and acceptable to give TARA to Swedish medical students and they described the program as an uncommon meeting ground for personal empowerment. Support was found for the four-factor structure of RADS-2, and the scale demonstrated good validity and acceptable to good reliability. The clinical pilot study further supported the feasibility and clinical safety of TARA, and preliminary signs of effectiveness were seen. A detailed description of the pragmatic, multicenter, randomized controlled superiority trial that will evaluate the clinical effectiveness of TARA compared to standard treatment for depression was outlined, peer reviewed, and published in a study protocol with a statistical analysis plan.
Conclusions: The present results indicate that TARA is feasible and safe in Swedish clinical and non-clinical contexts. RADS-2 is a suitable outcome measure to use in routine clinical practice as well as in the present and future trials of depression. The initiated randomized controlled trial will be an important next step logically following the studies and results presented in this dissertation.
- Exploring genomic and phenotypic differences in Neisseria meningitidis – understanding carriage and invasive disease Link: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112752
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Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222636
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to paresis, muscle atrophy, and respiratory failure. ALS can be difficult to diagnose and prognosticate early.
Aim: To investigate the diagnostic and prognostic characteristics of biomarkers in cerebrospinal fluid (CSF), plasma, and skeletal muscle tissue in patients with ALS.
Paper I: Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) were analyzed in CSF using enzyme-linked immunosorbent assay (ELISA), and NFL in plasma was analyzed using single-molecule array (SIMOA). CSF NFL, CSF pNFH, and plasma NFL concentrations can differentiate ALS patients from ALS mimics, and were significantly negatively correlated with the disease duration in ALS patients.
Paper II: Myosin heavy chain (MyHC) isoforms in extraocular muscles were investigated using immunofluorescence. Control donors had significantly higher proportion of myofibers containing MyHCIIa and significantly lower proportion of myofibers containing MyHCeom in the global layer compared to spinal-onset ALS and bulbar-onset ALS donors. Disease duration in the spinal-onset ALS donors was significantly correlated with the proportion of myofibers containing MyHCIIa in the global layer and MyHCeom in the orbital layer.
Paper III: The study combined the neurofilament concentrations from Paper I, with cytokines previously analyzed in CSF and plasma using SIMOA, to investigate distinct molecular phenotypes in ALS. Patients with bulbar-onset ALS had significantly higher concentrations of CSF tumor necrosis factor α (TNF-α) compared to ALS mimics. TNF-α and NFL were significantly correlated with each other in both CSF and plasma in ALS patients. Combined analysis of NFL and IL-6 in plasma identified molecular prognostic subgroups in ALS patients.
Paper IV: Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, and cystatin C (CysC) were analyzed in plasma in a fully accredited laboratory. CK and hs-cTnT concentrations were significantly elevated in limb-onset ALS compared to controls and bulbar-onset ALS. hs-cTnT concentrations were significantly elevated in truncal-onset ALS compared to controls and bulbar-onset ALS. Multivariable Cox proportional hazards models indicated elevated concentrations of CysC as a significant marker for worse prognosis in ALS.
Conclusions: The papers report diagnostic and prognostic characteristics of biomarkers in CSF, plasma, and muscle tissue in ALS patients. The significant findings for biomarkers in plasma could be of value since plasma sampling does not involve a lumbar puncture.