| 1. |
- 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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| 2. |
- Nielsen, Rasmus Oestergaard, et al.
(författare)
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Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises
- 2015
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Ingår i: MLTJ - Muscles Ligaments and Tendons Journal. - : Edra SpA. - 2240-4554. ; 5:4, s. 305-309
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity.Purpose: the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise.Methods: an explorative analysis was completed based on data from a randomized, controlled trial.The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline(pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle.Results: the collagen content of VL was similar between pre and post in the BRE group (-3.8 μg collagen/mg protein [95% CI: -22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: -0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: -6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (-9.3 μg collagen/mg protein [95% CI: -24.9; 6.4], p=0.25) or in the BRE group (-6.5 μg collagen/mg protein [95% CI: -25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference -2.78 μg collagen/mg protein[95% CI: -29.7; 24.1], p=0.82).Conclusion: muscle collagen content in the VL or SOL muscle does not seem to differ after a 90-day bed rest period with or without squat exercises.
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| 3. |
- Thornell, Lars-Eric, et al.
(författare)
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Fibre typing of intrafusal fibres
- 2015
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Ingår i: Journal of Anatomy. - : John Wiley & Sons. - 0021-8782 .- 1469-7580. ; 227:2, s. 136-156
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Forskningsöversikt (refereegranskat)abstract
- The first descriptions of muscle spindles with intrafusal fibres containing striated myofibrils and nervous elements were given approximately 150years ago. It took, however, another 100years to establish the presence of two types of intrafusal muscle fibres: nuclear bag and nuclear chain fibres. The present paper highlights primarily the contribution of Robert Banks in fibre typing of intrafusal fibres: the confirmation of the principle of two types of nuclear bag fibres in mammalian spindles and the variation in occurrence of a dense M-band along the fibres. Furthermore, this paper summarizes how studies from the Umea University group (Laboratory of Muscle Biology in the Department of Integrative Medical Biology) on fibre typing and the structure and composition of M-bands have contributed to the current understanding of muscle spindle complexity in adult humans as well as to muscle spindle development and effects of ageing. The variable molecular composition of the intrafusal sarcomeres with respect to myosin heavy chains and M-band proteins gives new perspectives on the role of the intrafusal myofibrils as stretch-activated sensors influencing tension/stiffness and signalling to nuclei.
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| 4. |
- Bojmar, Linda
(författare)
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Metastatic Mechanisms in Malignant Tumors
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ultimate cause of cancer related deaths is metastasis. This thesis is about three of the main human cancers; breast, colorectal and pancreatic cancer, that together account for more than 25% of the cancer-related deaths worldwide. The focus of the thesis is the spread of cancer, metastasis, and the aim was to investigate mechanisms that can be of importance for this process. We analyzed patient samples to validate the role of epithelialto-mesenchymal transition in vivo and found regulations of many related factors. However, these changes tend to fluctuate along the metastatic process, something which makes targeting complicated. We, moreover, focused on the influence of the tumor microenvironment for metastatic spread. In pancreatic cancer, the stroma constitutes the main part of many tumors. We analyzed the crosstalk between tumor and stromal cell and focused on the mediating inflammatory factor interleukin-1 (IL-1) and regulation of microRNAs. The results showed that the most commonly mutated factor in pancreatic cancer, KRAS, associates with the expression of IL-1 and subsequent activation of stromal cells. Blocking KRAS signaling together with IL-1 blockage give a more pronounced effect on in vitro proliferation and migration of cancer cells and suggests the use of a combination therapy. The cancer-associated activation of the stroma was found to be related to changes in microRNA expression. microRNA was analyzed separately in epithelial cells and stromal cells after microdissection of matched samples of primary and secondary tumors of breast and colorectal cancers. miR-214 and miR-199a were upregulated in stroma associated with progressive tumors and in pancreatic cancer stroma we could show that their expression alters the activation of stromal cells and thereby the growth and migratory ability of associated pancreatic tumor cells. In breast and colorectal cancers we found several common microRNAs to be up- or downregulated in line with progression. We could show that one of these candidates, miR-18a, had a prognostic value in metastatic breast cancer. To further develop these studies we analyzed this microRNA in circulating microvesicles, i.e. exosomes, and investigated their role in the preparation of a pre-metastatic niche. MicroRNAs are stable biomarkers in the circulation, especially protected in exosomes, which can moreover specifically deliver their message to recipient cells. These studies facilitate the understanding of metastatic behavior and suggest new targets to stop cancer metastasis.
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| 5. |
- Bojmar, Linda, et al.
(författare)
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miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.
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| 6. |
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| 7. |
- Edmundsson, David S., et al.
(författare)
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Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy
- 2018
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Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 57:2, s. 229-239
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Muscle changes in patients with diabetes and lower leg pain due to chronic exertional compartment syndrome (CECS) were investigated before and after fasciotomy.Methods: The tibialis anterior muscle was analyzed with histochemical and morphological techniques in 7 patients with diabetes and CECS before fasciotomy and in 5 of them 1 year after fasciotomy. Nondiabetic patients with CECS and healthy participants served as references.Results: Before treatment, walking distance until occurrence of pain was limited (<0.2 km). Intramuscular pressure was significantly higher than in reference participants. Muscle analysis showed changes pathognomonic for neuropathy and myopathy and a restricted capillary network, with significantly more severe changes in the muscles of patients with diabetes than in the muscles of nondiabetic patients. Treatment with fasciotomy improved clinical signs, increased walking ability, and reduced muscle abnormalities, but muscle capillarization remained low.Discussion: Patients with diabetes and CECS have distinct pathological changes in affected muscles. Pressure-relieving fasciotomy triggers a regenerative response in the muscle tissue but not in the capillary bed.
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| 8. |
- Ehinger, Anna, et al.
(författare)
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Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013
- 2017
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 56:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background: The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the Luminal A-like and Luminal B-like (HER2-negative) subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined. Patients and methods: Six hundred seventy-one patients (amp;gt;= 35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included. Results: Luminal A-like tumors were mostly G1 or G2 (90%) whereas Luminal B-like tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In Luminal B-like tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 Luminal A-like tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively. Conclusions: Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of Luminal A-like, while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of Luminal B-like, when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.
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| 9. |
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| 10. |
- Ekstedt, Mattias, et al.
(författare)
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Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
- 2015
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Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554
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Tidskriftsartikel (refereegranskat)abstract
- Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.
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