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- Frykholm, Erik, 1985-
(författare)
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The relevance and assessment of limb muscle function in individuals with chronic obstructive pulmonary disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD.Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2).Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49).Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity.
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| 2. |
- Harandi, Vahid M., 1985-
(författare)
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A Muscle Perspective on the Pathophysiology of Amyotrophic Lateral Sclerosis : Differences between extraocular and limb muscles
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disorder. ALS has been traditionally believed to be primarily a motor neuron disease. However, accumulating data indicate that loss of contact between the axons and the muscle fibres occurs early; long before the death of motor neurons and that muscle fibres may initiate motor neuron degeneration. Thus, the view of ALS is changing focus from motor neurons alone to also include the muscle fibres and the neuromuscular junctions (NMJs). While skeletal muscles are affected in ALS, oculomotor disturbances are not dominant features of this disease and extraocular muscles (EOMs) are far less affected than limb muscles. Why oculomotor neurons and EOMs are capable to be more resistant in the pathogenetic process of ALS is still unknown.The overall goal of this thesis is to explore the pathophysiology of ALS from a muscle perspective and in particular study the expression and distribution of key neurotrophic factors (NTFs) and Wnt proteins in EOMs and limb muscles from ALS donors and from SOD1G93A transgenic mice. Comparisons were made with age-matched controls to distinguish between changes related to ALS and to ageing.Results: Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4) were present in EOMs and limb muscles at both mRNA and protein levels in control mice. The mRNA levels of BDNF, NT-3 and NT-4 were significantly lower in EOMs than in limb muscles of early and/or late control mice, indicating an intrinsic difference in NTFs expression between EOMs and limb muscles. qRT-PCR analysis showed significantly upregulated mRNA levels of NT-3 and GDNF in EOMs but significantly downregulated mRNA levels of NT-4 in limb muscles from SOD1G93A transgenic mice at early stage. The NTFs were detected immunohistochemically in NMJs, nerve axons and muscle fibres. The expression of BDNF, GDNF and NT-4 on NMJs of limb muscles, but not of EOMs, was significantly decreased in terminal stage ALS animals as compared to the limb muscles of the age-matched controls. In contrast, NTFs expression in intramuscular nerve axons did not present significant changes in either muscle group of early or late ALS mice. NTFs, especially BDNF and NT-4 were upregulated in some small-sized muscle fibres in limb muscles of late stage ALS mice. All the four Wnt isoforms, Wnt1, Wnt3a, Wnt5a and Wnt7a were detected in most axon profiles in all human EOMs with ALS, whereas significantly fewer axon profiles were positive in the human limb muscles except for Wnt5a. Similar differential patterns were found in myofibres, except for Wnt7a, where its expression was elevated within sarcolemma of limb muscle fibres. β-catenin, a marker of the canonical Wnt pathway was activated in a subset of myofibres in the EOMs and limb muscle in all ALS patients. In the SOD1G93A mouse, all four Wnt isoforms were significantly decreased in the NMJs at the terminal stage compared to age matched controls.Conclusions: There were clear differences in NTF and Wnt expression patterns between EOM and limb muscle, suggesting that they may play a role in the distinct susceptibility of these two muscle groups to ALS. In particular, the early upregulation of GDNF and NT-3 in the EOMs might play a role in the preservation of the EOMs in ALS. Further studies are needed to determine whether these proteins and the pathways they control may be have a future potential as protecting agents for other muscles.
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| 3. |
- Levin, Sara, 1974-
(författare)
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The challenges of using structured risk assessment instruments in forensic psychiatric care
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The purpose of psychiatric forensic care is to provide treatment for mentally ill offenders and to prevent future acts of violence and other adverse events. During care, the type of restrictions of freedom, the patient’s continuous need for involuntary treatment and readiness for discharge, are continuously evaluated based on the assessment of risk the patient pose to themselves and others as well as the progress achieved with treatment. The use of structured risk assessment instruments is recommended in clinical guidelines to assess such risks. However, unstructured clinical assessments, considered to be less valid, are often used in clinical practice. There is insufficient research evidence concerning several aspects related to the clinical use of structured risk assessment instruments in terms of guiding the planning and realization of care and risk management interventions. There is also a lack of knowledge about what patients themselves perceive to be mediating factors for their use of violence. Overall aim: The overarching aim of this thesis was to investigate the implementation and use of structured risk assessment instruments to prevent violence and other adverse events in forensic settings and to improve understanding of the factors that influence such events among forensic patients.Methods: Several methods were used for data collection and data were analysed by different types of content analysis. In the first paper, a systematic review of previous research studies on implementation determinants for structured risk assessment instruments in forensic settings was conducted to investigate implementation determinants for such instruments. The second paper evaluates a pilot project of the implementation of a structured risk assessment instrument at a forensic clinic in Östergötland using focus group interviews with staff members who had used the instrument. Their perceptions of the instrument and barriers and facilitators to its implementation and clinical use were investigated. The third paper investigated the actual clinical use of structured risk assessments to guide the planning and realization of care and risk management interventions documented in forensic patients’ records. In the fourth paper, patient perspectives of factors increasing and decreasing the risk for violence were investigated by individual semi-structured interviews with forensic patients.Results: There is a wide variety of determinants for the implementation and clinical use of structured risk assessment instruments, which make such missions complicated. The determinants relate to the characteristics of the implementation object, characteristics of users, the inner setting in which the implementation occurs and the implementation process. Limiting the need to change current routines, and hence the strain on the organization by reducing complexity, and the need for resource allocation seem especially important. Most of the planned risk management interventions in structured risk assessments were realized according to patient records. However, structured risk assessments largely overlap with unstructured risk assessments in terms of planned care and risk management interventions. Noteworthy, most of the interventions realized were not documented as planned. Forensic patients described several risk factors that increased and decreased their use of violence. These factors related to themselves, external influences, social and relational aspects and situational factors. Most patient accounts of mediating factors overlapped with those listed in commonly used risk assessment instruments and previous research. Additional factors identified by patients related to the outer context and interpersonal aspects.Conclusions: There are many barriers and facilitators to the implementation and use of structured risk assessment instruments, implying the need for a multifaceted approach to address determinants at several system levels. Considering the clinical context is important when selecting a structured risk assessment instrument to be implemented, but also the complexity of the instrument, the required change of routines and the provision of continuous resources and interventions to achieve and maintain clinical use. Despite the many barriers, there is evidence of clinical use of both unstructured clinical and structured risk assessments in terms of informing and guiding care and risk management interventions. The large overlap, however, makes it difficult to draw definite conclusion about which type of assessment actually influenced the interventions that were realized. Realized care and risk management interventions are most often not documented as planned. This increases the risk of subjective decisions and provision of interventions, which also make such interventions difficult to evaluate. Forensic patients are actively managing their risk of violence and are capable of identifying and communicating many different mediating factors for their violence risk. They are knowledgeable and important stakeholders and should be involved in their own risk assessments, as well as in research.
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