To Örebro University

Purpose: The study objective was to investigate how health care providers in stroke teams reason about their clinical reasoning process in collaboration with the patient and next of kin.

Materials and methods: An explorative qualitative design using stimulated recall was employed. Audio-recordings from three rehabilitation dialogs were used as prompts in interviews with the involved staff about their clinical reasoning. A thematic analysis approach was employed.

Results: A main finding was the apparent friction between profession-centered and person-centered clinical reasoning, which was salient in the data. Five themes were identified: the importance of different perspectives for a rich picture and well-informed decisions; shared understanding in analysis and decision-making - good intentions but difficult to achieve; the health care providers' expertise directs the dialog; the context's impact on the rehabilitation dialog; and insights about missed opportunities to grasp the patient perspective and arrive at decisions.

Conclusions: Interprofessional stroke teams consider clinical reasoning as a process valuing patient and next of kin perspectives; however, their professional expertise risks preventing individual needs from surfacing. There is a discrepancy between professionals' intentions for person-centeredness and how clinical reasoning plays out. Stimulated recall can unveil person-centered practice and enhance professionals' awareness of their clinical reasoning.

Background: Although person-centered care is prioritized in healthcare, challenges remain before such care is integrated in everyday communication and practice. One way to strengthen person-centered care is that health professionals’ clinical reasoning (i.e., assessment and management) is pervaded by patient participation and individualized to patient needs. Interprofessional team meetings, focusing on goals and management planning, is an opportunityt o improve person-centeredness. However, there is a lack of understanding of how person-centeredness is created in the clinical reasoning of teams. This study aims to explore how clinical reasoning is performed from a person-centered perspective in team meetings with patients with stroke and next of kin.

Methods: Explorative qualitative design employing a thematic analysis of audio recorded communication at three team meetings. In total, three patients, two next of kin, and 15 professionals representing eight health professions, participated in the meetings.

Findings: Four themes and eight subthemes were established: a) Emphasizing the patient’s resources; b) Struggling to find a common understanding, including subthemes: Unite the person’s narrative, the relative’s view, and the expertise of the interprofessional team, missed opportunities to clarify patient needs and wishes, and active listening and receptiveness; c) Balancing the patient’s goals and professionals’ goals, including subthemes: Shared goals, the professionals’ view of appropriate goals, and the professionals’ assessment governs achievement of goals; d) Ambiguity in decisions about the management plan, including subthemes: Initiating shared decision making and lack of clarity and consensus.

Discussion: This study reveals how the patient, next of kin and team contribute to shared understanding of the patient’s problem. Goals were guided by the patient’s and professionals’ expertise. To improve person-centeredness in clinical reasoning, the team need to further put the patient’s personal goals and perception of goal-achievement in the forefront as well as improve communication skills to catch patient needs and facilitate shared decisions.

OBJECTIVE: Fibrin has been used as a standard material for scaffold fixation during cartilage repair surgery. Most of the commercially available fibrin preparations need an additional method for scaffold fixation, most often with sutures, thus damaging the surrounding healthy cartilage. There is therefore a need to find alternatives to this method. In our study, we have investigated the potential possibility to use mussel adhesive protein as such an alternative.

METHODS: In this study, hydrophobic plastic was coated with the mussel adhesive protein Mefp-1 as well as with other cell adhesives (poly-lysine, fibronectin, and collagen). Human keratinocytes and chondrocytes were seeded on these substrates at 37°C in culture medium, followed by analysis of attachment and proliferation by crystal violet staining and metabolic labelling. Performance of Mefp-1 and fibrin as tissue glues were estimated by tensional force resistance measurement of moist porcine dermis (as a correlate to scaffold) glued to dermis, cartilage, or bone at 37°C.

RESULTS: Mefp-1 supported maximal cell attachment at a coating density of approximately 1 µg/cm². This was at least as good as the other adhesives tested. In addition, it supported cell proliferation at least as good as regular tissue culture plastic over a 7-day period. Measurement of tensional force resistance showed that Mefp-1 performed equally well as fibrin when porcine dermis was glued to cartilage and bone at the same concentration. Separation of the moist tissues after 15-minute incubation required a force of approximately 1 N/cm² for both compounds.

CONCLUSIONS: Mefp-1 show properties that qualify it as a compound that potentially could replace fibrin as a tissue glue for scaffold fixation. Given the possibilities to modify this protein by bioengineering, it is likely that the properties can be further improved.

Aims and Objectives: To describe the variation of conceptions of being ill and hospitalised, from the perspective of health-care-professional-patients.

Background: Previous literature focuses on either physicians' or nurses' experiences of being a patient, without aiming at determining a variation of ways of understanding that phenomena. Nor have we been able to identify any study reporting other health-care-professionals' experiences.

Design: This study has an inductive descriptive design.

Methods: Qualitative interviews with health care professionals (n=16), who had been hospitalised for at least two days. Phenomenographic data analysis was conducted.

Results: The feelings of security were based on knowledge, insight and trust, and acceptance of the health care system. Being exposed and totally dependent due to illness provoked feelings of vulnerability and insecurity. The patients used their knowledge to achieve participation in the care. The more severe they perceived their illness to be, the less they wanted to participate and the more they expressed a need for being allowed to surrender control. The patients' ideal picture of care was sometimes disrupted and based on their experience they criticised care and made suggestions that could contribute to general care improvements.

Conclusions: Health-care-professional patients' have various conceptions of being ill and hospitalised. Based on the general nature of the many needs expressed, we believe that the some insights provided in this study can be transferred so as to also be valid for lay patients. Possibly, an overhaul of routines for discharge planning and follow-up, and adopting a person-centred approach to care, can resolve some of the identified shortcomings. Finally, the results can be used for the purpose of developing knowledge for health-care professions and for educational purposes.

Relevance to clinical practice: The results can be used for the purpose of develop-ing knowledge for healthcare professions and for educational purposes.

Objectives: To explore growth data (height-for-age, weight-for-age and BMI-for-age) of children living in poor socioeconomic conditions in rural areas of Chin State, Burma/Myanmar; and to compare these data with the growth and development z-score (GDZ) values for school-aged children and adolescents, provided by the WHO.

Setting: A support and educational programme, run by the Swedish association Chin Development and Research Society (CDRS), was carried out among underprivileged school-aged children, unable to attend school without economic and practical support, living in villages and remote areas in Chin State.

Participants: Community leaders who were well familiar with the citizens in the community identified children in need of this support. Other community members could also suggest or apply for this. The sample includes all participating children in the CDRS programme at the time of the data collection in six townships. The children were placed in host families, close to a suitable school. Two samples with a total of 639 children from 144 villages and remote areas were obtained:

1. Children in the CDRS Chin Programme (CCP) (20072010) comprised 558 children: 50% girls and boys.

2. Children in the Chin Society (CCS) (2010) comprised 81 children: 44% girls and 56% boys.

Primary outcome measures: Growth data.

Results: All growth data from both groups deviated significantly from the WHO standard references (p=0.001). The prevalence of stunting (height-for-age <=-2SD) was 52% among girls and 68% among boys. High levels of wasting (weight-for-age <=-2SD) were found among girls 29% and boys 36% aged 5-10 years. In addition, severe thinness (BMI-for-age <=-2SD) was found among girls 31% and boys 44%, all results to be compared to the expected 2.27%.

Conclusions: Many more than expected-according to the WHO reference values-in CCP and CCS suffered from stunting, wasting and thinness.

Objective: To explore healthcare professionals' conceptions of the care of patients who are also healthcare professionals.

Design: Explorative, with a qualitative, phenomenographic approach.

Participants and setting: 16 healthcare personnel within different professions (doctors, nurses, assistant nurses, physiotherapists, occupational therapists) were interviewed about the care of 32 patients who were themselves members of different healthcare professions, in one healthcare organisation in Sweden.

Results: The care of patients who are healthcare professionals was conceived in five different ways, as: usual, dutiful, prioritised and secure, insecure and responsive. An initial conception was that their care was usual, just as for any other patient, and also a perceived duty to treat them and to protect their right to be a patient-as any other patient. Exploring further, informants described that these patients did receive secure and prioritised care, as the informants experienced making a greater commitment, especially doctors giving privileges to doctor-patients. A conception of insecure care infused the informants' descriptions. This comprised of them feeling intimidated in their professional role, feeling affected by colleagues' stressful behaviour and ambiguity whether the healthcare professional-patient could be regarded as a competent professional. The deepest way of understanding care seemed to be responsive care, such as acknowledging and respecting the patient's identity and responding to their wishes of how treatment was to be met.

Conclusions: Caring for healthcare professionals seems to trigger different ethical approaches, such as deontology and ethics of care. According to ethics of care, the findings may indeed suggest that these patients should be cared for just as any other patients would be, but only if this means that they are cared for as persons, that is, they are given 'person-centred care'. This would imply balancing between acknowledging the vulnerable patient in the colleague and acknowledging the identity of the colleague in the patient.

Healthcare professionals' experience of being family member of a patient can contribute to knowledge development and organizational learning in further ways than the experiences of general family members. However, there is little research on healthcare professionals' experience being on 'the other side of the bed'.

Objective: To describe how healthcare professionals understand the role of being a healthcare professional and a family member of a patient admitted to hospital.

Design: Qualitative with a phenomenographic approach.

Setting: Three Swedish hospitals.

Participants: All healthcare professionals in three hospitals were invited. Twenty-one volunteered for the study and 18 met the inclusion criteria; to have one year of professional experience and to have visited the family member in hospital daily during hospitalization. Family members in maternity or psychiatric care were excluded.

Methods: Semi-structured interviews were used for data collection. Transcripts were analyzed with a phenomenographic method to describe variation and commonality in the ways of understanding the phenomenon under study.

Results: Four dominant ways of understanding the phenomenon were identified; the informed bystander, the supervisor, the advocate and the carer. The four ways of understanding were hierarchically related with "The informed bystander" being least involved in the care of the family member and "The carer" more or less taking over the patient's care because of inappropriate, unsafe or omitted care. Common for all ways of understanding the phenomenon, except "The informed bystander", was the difficult balance between their loyalty toward the family member and their colleagues among the staff. "The informed bystander" and "The supervisor" are ways of understanding the phenomenon under study that, to our knowledge, has not been described before.

Conclusions: This study describes how being a family member of a patient can be understood in four different ways when the family member is a healthcare professional. The findings show similarities to previous studies on general family members as well as nurse-family members of patients in critical care. The need for professional communication, support and coordination will be substantially different if the family member understands his/her role as an informed bystander compared to if they perceive themselves as a carer. The role conflict and ambivalence toward building relationships described are aspects that need further exploration, as does the experience of being forced to care for a family member. Our findings contribute with new knowledge developing patient- and family-centered care.

Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.

Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).

Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.

Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.

In this thesis focus has been to increase the knowledge and understanding of some of the mechanisms responsible for drug resistance in acute myeloid leukemia, as well as identify possibilities to predict drug resistance at diagnosis.

We have studied the intracellular behavior of cytostatic drugs and their main metabolites (paper I) and the cellular response to cytostatic drugs (paper III). A new flow cytometry in vitro chemosensitivity assay was developed, to enable identification of viable myeloid cells and determination of drug sensitivity (paper II). Finally, possible new markers involved in drug resistance were investigated (paper IV).

In conclusion we found that idarubicin and daunorubicin are equally toxic at the same intracellular concentrations. The contribution of the main metabolites to the cytotoxic effects of idarubicin and daunorubicin, in both drug sensitive and drug resistant human myeloid leukemia cells, is low. It is most likely the pharmacokinetic properties of idarubicin and daunorubicin that confer their main cytotoxic effect. With the new flow cytometry chemosensitivity assay we selectively identified viable CD13/CD33 expressing myeloid cells and found that the cytotoxicity results correlated to clinical parameters, such as secondary AML and resistant disease. Short-term exposure of leukemia cell lines with different levels of drug resistance to ara-C revealed that Pgp mRNA and protein ex-pression levels, as well as GSTπ mRNA levels, were rapidly up-regulated. Clinically, this up-regulation may be of importance for the sequential scheduling of daunorubicin and ara-C during the induction treatment of AML. CRIM1 has

never been studied in the context of drug resistance before. We show for the first time that baseline expression of CRIM1 mRNA is much higher in drug resistant leukemia cells compared to drug sensitive cells. We also found a co-variance between CRIM1 and Pgp mRNA expression levels in leukemia cell lines with different levels of drug resistance, suggesting that CRIM1 may be useful as a marker of drug resistance.