No description available.

Background and aims. Patients’ consultations with GPs can deal with a wide range of conditions and problems. Generally, consultation outcomes have been considered in evaluations but outcome has a meaning for elaboration of care beyond the graduating role of quality and other evaluation instruments. Knowledge about outcomes is needed for understanding and development. The aim of this thesis was to investigate outcomes of GPs’ consultations as directly experienced by patients and GPs and to investigate connections between clinical strategies and presumed patient outcomes. Methods. First, concepts describing outcomes from patients’ and GPs’ viewpoints were developed from interviews in groups and individually. Secondly, based on this, questionnaires about the consultation outcomes were formulated. Then, patients and GPs answered questionnaires regarding the same recent consultation. The numbers of the different outcomes were counted and the experiences of outcomes from the same consultations were compared. Finally, another questionnaire including both the GP outcome questions and questions about the clinical situation and decisions made was answered by GPs. Results. Concepts describing consultation outcomes were brought forward. Cure/symptom relief, reassurance, patient understanding and satisfaction were used by both patients and GPs to describe outcome of consultations. Only patients described as outcomes a confirmation of their ideas and a change in self-perception. GPs, but not patients, described the patient outcomes in terms of check-up and coping. Besides this, GPs also described other outcomes that concerned relationship-building, a change of surgery routines and self-evaluation. Selfevaluation was related to a perceived collegial consensus about right and wrong. The concordance between GPs and patients assessing the same consultations was high for satisfaction, intermediate for patient understanding and low for belief in cure/symptom relief. Clinical strategies were linked to outcomes. Immediate problem solving was registered in about half the consultations. When immediate problem solving was registered the patients were supposed to be more reassured, satisfied and coped better than after gradual problem solving. With increasing psychosocial content of the consultation the GPs registered more dissatisfaction both for themselves and their patients. Conclusions. Change in self- perception was a prominent patient outcome. GPs’ self-evaluations ought to have the inherent possibility to serve as a basis for development of general practice. The entire map of the encountered outcome concepts can serve as a basis for further research and development. The mapping of concepts can be of help when prioritising. Knowledge about the total picture of consultation outcomes can help the GP to understand the patients’ worlds better. It can also contribute to a realistic picture of possible consultation outcomes. The GPs seemed to adjust their problem solving (immediate or gradual) to the registered problem and furthermore adjust the immediate problem solving, focusing either on the problem or on the patient as a person.

Alpha1‐acid glycoprotein (AGP) is a highly glycosylated lipid‐binding acute‐phaseprotein. Although the exact mechanisms are unknown, several studies havesuggested that AGP may regulate the function of neutrophils and hence modulateinflammatory responses. The general aim of this thesis was to investigate if AGP isable to mediate intracellular signalling in neutrophils through binding to specificreceptors. Measurements of intracellular calcium concentration showed that AGP elicited asmall rise in [Ca2+]i in neutrophils that was markedly enhanced by pre‐treatmentwith anti‐L‐selectin antibodies. In contrast, desialylation of AGP reduced the Ca2+mobilizing capacity significantly. The AGP‐induced Ca2+ signal was mediatedthrough Src tyrosine kinases, PLC and PI3K which suggests involvement of cellsurface receptors. Indeed, AGP was shown to bind to, and mediate Ca2+ signallingthrough, sialic acid binding immunoglobulin‐like lectin (Siglec)‐5 and/or ‐14.Increased fucosylation of AGP is common during acute‐phase reactions. We showthat hyperfucosylated AGP has a diminished Ca2+ signalling capacity compared tonormally fucosylated AGP. This could be due to a reduced capacity of AGP tointeract with Siglec‐5/‐14 since it is known that the presence of fucose residues onsialylated glycans has a negative effect on Siglec‐5/‐14 affinity. AGP was alsodemonstrated to bind to the neutrophil proteins S100A8 and S100A9. In additionwe show that AGP‐bound hydroxyeicasotetraenoic acids (HETEs) induce increasesin [Ca2+]i in neutrophils through binding to the leukotriene B4 receptor BLT2. Wepropose a two‐step binding model where AGP binds to Siglec‐5/‐14 on L‐selectinactivated neutrophils. This may orient AGP in a way that assists an interactionbetween AGP and the neutrophil membrane which favours transfer of AGP‐boundHETEs to the BLT2 receptor. In conclusion, these data gives new insights regarding how AGP interacts with andmediates signalling in human neutrophils and supports the view of AGP as beingan acute phase reactant with immunomodulatory properties.

During pregnancy, fetal tolerance has to be achieved without compromising the immune integrity of the mother. CD4+CD25highFoxp3+ regulatory cells (Tregs) have received vast attention as key players in immune regulation. However, the identification of human Tregs is complicated by their similarity to activated nonsuppressive T cells. The general aim of this thesis was to determine the antigen specificity, frequency, phenotype and function of Tregs in first to second trimester healthy and severe early-onset preeclamptic human pregnancy. Regarding antigen specificity, we observed that in healthy pregnant women, Tregs suppressed both TH1 and TH2 reactions when stimulated with paternal alloantigens but only TH1, not TH2 reactions when stimulated with unrelated alloantigens. Hence, circulating paternal-specific Tregs seem to be present during pregnancy. Further, by strictly defining typical Tregs (CD4dimCD25high) using flow cytometry, we could show that as a whole, the Treg population was reduced already during first trimester pregnancy as compared with non-pregnant women. This was in contrast to several previous studies and the discrepancy was most likely due to the presence of activated non-suppressive cells in pregnant women, showing similarities to the suppressive Tregs. Although deserving confirmation in a larger sample, severe early-onset preeclampsia did not seem to be associated with alterations in the circulating Treg population. The circulating Treg population was controlled by hormones which, alike pregnancy, reduced the frequency of Foxp3 expressing cells. Yet, in vitro, pregnancy Tregs were highly suppressive of pro-inflammatory cytokine secretion and showed an enhanced capability of secreting immune modulatory cytokines such as IL-4 and IL-10, as well as IL-17, indicating an increased plasticity of pregnancy Tregs. At the fetalmaternal interface during early pregnancy, Tregs, showing an enhanced suppressive and proliferating phenotype, were enriched as compared with blood. Further, CCR6- TH1 cells, with a presumed moderate TH1 activity were enhanced, whereas pro-inflammatory TH17 and CCR6+ TH1 cells were fewer as compared with blood. This thesis adds to and extends the view of Tregs as key players in immune regulation during pregnancy. In decidua, typical Tregs seem to have an important role in immune suppression whereas systemically, Tregs are under hormonal control and are numerically suppressed during pregnancy. Further, circulating pregnancy Tregs show reduced expression of Foxp3 and an increased degree of cytokine secretion and thereby also possibly plasticity. This would ensure systemic defense against infections with simultaneous tolerance at the fetal-maternal interface during pregnancy.

Many patients are diagnosed as having chronic heart failure (CHF) and apart from the fact that daily activities are impaired, they are great consumers of health care, and the prognosis is poor. The distinction between acute heart failure (AHF) and CHF may be difficult and is more a question of time rather than severity. The “gold standard” treatment for end‐stage heart failure is heart transplantation. Due to organ shortage this is reserved for selected patients only. Since the introduction of mechanical circulatory support (MCS) more and more patients with progressive CHF have been bridged‐to‐heart‐transplantation. There are MCS systems available for both short‐ and long‐term support. Newer concepts such as ventricular constraint to prevent ventricular remodelling are on the way. We have investigated short‐ (ImpellaTM) and long‐term (HeartMateTM I and II) MCS and ventricular constraint (CorCapTM CSD) as treatment concepts for all forms of heart failure, the aims being: bridge‐to‐decision, bridge‐to‐transplant and extended therapy, called “destination therapy” (DT). Methods and results: In Paper I, the use of HM‐ITM pulsatile MCS in bridge‐to‐transplantation patients in Sweden was retrospectively investigated regarding outcome and risk factors for mortality and morbidity. Fifty‐nine patients were treated between 1993 and 2002. The dominating diagnosis was dilated cardiomyopathy in 61%. Median support time was 99.5 days. 18.6% died before transplantation. Four patients needed RV assist due to right ventricular failure. Haemorrhage was an issue. Six patients (10%) suffered a cerebrovascular thromboembolic lesion. 15% developed driveline infection. 45% of the MCS patients were discharged home while on pump treatment. Massive blood transfusion was a predictor for mortality and morbidity, p<0.001. In Paper II the second generation long‐term MCS, the continuous axial flow pump HM‐IITM, was prospectively evaluated for mortality and morbidity. Eleven patients, from 2005 until 2008, were consecutively included at our institution. One patient received the pump for DT. The median pump time was 155 days. Survival to transplantation was 81.8%. Ten patients could be discharged home before transplantation after a median time of 65 days. Paper III investigated the Swedish experience and outcome of short‐term axial flow MCS, the ImpellaTM, in patients with AHF. Fifty patients were collected between 2003 and 2007 and divided into two groups: 1. Surgical group (n=33) with cardiogenic shock after cardiac surgery; and 2. Non‐surgical group (n=17), patients with AHF due to acute coronary syndromes with cardiogenic shock (53%) and myocarditis (29%). The 1‐year survival was 36% and 70%, respectively. 52% were reoperated because of bleeding. Predictors for survival at 30 days were preoperatively placed IABP (p=0.01), postoperatively cardiac output at 12 hours and Cardiac Power Output at 6 and 12 hours. In Paper IV we evaluated the use and long term outcome of ventricular constraint CorCapTM CSD. Since 2003, 26 consecutive patients with chronic progressive heart failure were operated with CSD via sternotomy (n=25) or left mini‐thoracotomy (n=1). Seven patients were operated with CorCapTM only. Nineteen patients had concomitant cardiac surgery. There were three early and three late deaths. The remaining cohort (n=18) was investigated in a cross‐sectional study regarding QoL with SF‐36. There was no difference in QoL measured with SF‐36 after a mean 3‐years follow up period, when compared to an age‐ and sex‐matched control group from the general population. The one‐year survival was 86%, and after three years 76%. Echocardiographic dimensions had improved significantly after three years. Conclusion: In our unit, a non‐transplanting medium‐sized cardiothoracic department, short‐ and long‐term MCS (ImpellaTM resp. HMTM) in patients with acute or chronic HF have been used with good results. The use of ventricular constraint early in the course of the disease is a good adjunct to other treatment options in progressive chronic HF patients.

The ultimate goal in major incidents is to optimize care for the greatest number of patients. This means matching patients with facilities that have the appropriate resources available in sufficient quantities to provide the necessary care. A major incident is a situation where the available resources are inadequate in relation to the urgent need. As health care resources have become increasingly constrained, it is imperative that all resources be optimized from a regional and sometimes a national perspective. In Sweden, the number of major incidents per year is still unknown. In order to implement effective quality control of response to major incidents, specific standards for regional medical response need to be set and agreed on from a national perspective. This will probably also enhance follow-up and comparison of major incidents in the future. The overall aim of this thesis is to improve understanding of the demand for rapid and accurate regional medical response at major incidents. The objectives were to systematically analyse specific decisions within regional medical response and to identify factors that can influence patient outcome in major incidents. This research is based on four studies in which a set of 11 measurable performance indicators for initial regional medical command and control have been used as an evaluation instrument together with a simulation system where the assessment of each patient could be evaluated. The collection of data was made during several disaster management programs but also in real major incidents that occurred in two county councils in Sweden. In one of the studies, the national disaster medical response plan for burns was evaluated. This research shows that measurable performance indicators for regional medical response allow standardized evaluation such that it is possible to find crucial decisions that can be related to patient outcome. The indicators can be applied to major incidents that directly or indirectly involve casualties provided there is sufficient documentation available and thereby could constitute a measurable part of regional and national follow-up of major incidents. Reproducible simulations of mass casualty events that combine process and outcome indicators can create important results on medical surge capability and may serve to support disaster planning. The research also identified that there is a risk for delay in distribution of severely injured when many county councils needs to be involved due to different regional response times to major incidents. Furthermore, the coordination between health care and other authorities concerning ambulance helicopter transport in mass casualty events needs to be further addressed. It is concluded that there is a demand for rapid and accurate response to major incidents that is similar in all county councils. Like all other fields of medicine, these processes need to be quality assured.

Ungefär en fjärdedel av Sveriges befolkning upplever arbetsrelaterade besvär. De vanligaste orsakerna för arbetsrelaterad ohälsa är orsakade av fysiska brister i arbetsmiljön. Samtidigt ökar bristerna i den psykosociala arbetsmiljön. Det har funnits skillnader mellan kvinnor och mäns arbetsrelaterade besvär under en lång tid, kvinnor drabbas i högre utsträckning av arbetsmiljöbesvär och glappet mellan kvinnor och män blir större. Olika yrken i Sverige rapporterar i olika grad arbetsrelaterad ohälsa på grund av psykosomatiska besvär. Brister rapporteras i hög utsträckning av förskolelärare.  Arbetsmiljöverkets ramlag Organisatorisk och social arbetsmiljö AFS (2015:14) tydliggör begreppet psykosocial arbetsmiljö och bryter ner begreppet till organisatorisk och social arbetsmiljö. Med avsikten att flytta arbetsmiljöansvaret från individ till arbetsgivare. Organisatorisk arbetsmiljö definieras som: ”Villkor och förutsättningar för arbetet som inkluderar, Ledning och styrning, Kommunikation, Delaktighet och handlingsutrymme, Fördelning av arbetsuppgifter och Krav, resurser och ansvar” (Arbetsmiljöverket, 2015a). Organisatoriska faktorer innebär de ramverk som finns för att organisera den psykosociala arbetsmiljön. Syftet i denna studie är att undersöka chefers erfarenheter om vad som bidrar till en god organisatorisk arbetsmiljö inom förskolan. För att besvara syftet användes kvalitativ metod. Fem semistrukturerade intervjuer med förskolechefer utfördes. Innehållsanalysen som tillämpats har varit en blandning av deduktiv och induktivt ansats. Studiens resultat visar att en god organisatorisk arbetsmiljö skapas av struktur. Rutiner som klargör hur och när kommunikationen mellan medarbetare och chef ska ske. Fler framgångsfaktorer var att skapa gemensamma mål och visioner men även att fördela arbetsområden och ansvar. Men också att arbeta med ett gemensamt förhållningssätt i verksamheten. Nyckelord:  Chefsperspektiv, Från individ - till organisationsperspektiv, God organisatorisk arbetsmiljö, Kvalitativa intervjustudier.

No description available.

Asthma and chronic obstructive pulmonary disease (COPD) are two common inflammatory airway diseases characterized by airway inflammation and mucus hypersecretion. Prediction of the outcome of these diseases may not be performed and the need for non-invasive diagnostic tools capable of identifying inflammation in asthma and COPD becomes therefore obvious. Validation, sensitivity and specificity of most non-invasive methods to detect and monitor inflammatory responses in airways are poor and there is a great need to identify and standardize less invasive, or non-invasive methods for investigation of airway inflammation. Epithelial lining fluid (ELF) covers the airway surface and contains soluble and insoluble inflammatory cell products and plasma proteins originating and passively transferred from the underlying tissue. Airborne aerosol particles containing ELF saturated with water may be recovered in exhaled air by allowing the air to pass a cold surface, creating exhaled breath condensate (EBC). EBC may then be analysed for various components of interest. The aims of this thesis were (1) to explore whether a certain profile of inflammatory cell markers in EBC, saliva or serum may be identified in patients with allergic asthma or COPD, (2) to evaluate the efficacy and reproducibility of a measurable marker in EBC using either of the two condensers ECoScreen or RTube and (3) to evaluate the value of chlorine concentrations in EBC as well as reproducibility of assessments of certain compounds in EBC. Material and methods: Thirty-six patients with asthma, 49 smokers or ex-smokers and 25 healthy volunteers participated in three clinical studies. In addition, efficacy, reproducibility and comparison of the two condensers were studied in an ex vivo set up using aerosols of solutions of saline, myeloperoxidase (MPO) or human neutrophil lipocalin (HNL). Aerosol boluses were transferred by means of a servo ventilator to either of the two condensers. Concentrations of chlorine (presumed to be a marker of mucous secretion) in EBC or saliva were analyzed by means of a sensitive coulometric technique (AOX). The inflammatory cell markers histamine, MPO, HNL, lysozyme, cysteinyl-leukotrienes (CysLT) and eosinophil cationic protein (ECP) were analysed in EBC, saliva and/or serum by means of ELISA, RIA, EIA or immunochemical fluorescence methods, respectively. Lung function tests, including diffusion capacity were measured by standard techniques according to clinical routines. Results and Conclusions: Chlorine measurements served as the main tool in our tests and intra-assay variability <10% was recorded. However, flow dependency, temperature dependency, substance dependency and concentration dependency characterized yields of EBC. Despite acceptable analytical precision, low concentration levels of inflammation markers, biological variability and occasionally contamination with saliva mean that the feasibility of the EBC method is limited. Despite biological variability, concentrations of chlorine in EBC were significantly higher during than after a mild pollen season, suggesting that chlorine concentrations in EBC are a sensitive marker of allergic airway inflammation. A vast number of confounding factors made interpretations of EBC data obtained from COPD and non-COPD patients difficult and traditional diagnostic tools, such as diffusion capacity (DLCO) and serum lysozyme appeared to best discriminate between COPD and non-COPD.

Background: Patients treated in an intensive care unit (ICU) are seriously ill, have a high co‐morbidity, morbidity and mortality. ICUs are resource – demanding as they consume significant hospital resources for a minority of patients. The development of new medical procedures for critical care patients has over the years led to survival of larger numbers with more complex illnesses and extensive injuries. Improved survival rates lead to needs for outcome measures other than survival. The present study examines health‐related quality of life (HRQoL) and factors assumed to be important for the long term HRQoL for former ICU patients. Methods: This is a multicenter cohort study of 980 adult patients admitted to one of three mixed medical‐surgical ICUs in Southern Sweden, during 2000 to 2004. The patients were studied at four different occasions after their critical illness: 6, 12, 24, and 36 months after discharge from the ICU and hospital. HRQoL was assessed by the EuroQol 5‐Dimensions (EQ‐5D) and Medical Outcome Short Form (SF‐36), sleep disturbances by the Basic Nordic Sleep questionnaire (BNSQ), and pre‐existing diseases was collected by self‐reported disease diagnosis. Data from a large public health survey (n=6093) of the county population were used as reference group. Results: Compared with the age and sex adjusted general reference group the patients who had been in the ICU had significantly lower scores on EQ‐5D and in SF‐ 36 all eight dimensions. This was seen both for the general ICU patients as well as for the multiple trauma patients. Significant improvement over time was seen only in single and separate dimensions for the general ICU group, and for the multiple trauma group. Long term effects of ICU care on sleep patterns were found minor as 70 % reported an unchanged sleep pattern and only 9% reported worse sleep after the IC period. Pre‐existing diseases were found to be the factor that had the largest influence on HRQoL in both the short‐ and long term perspective for the general ICU patients as well as for the multiple trauma patients. It was also found to have negative impact on sleep. IC ‐related factors showed only a minor influence on HRQoL or sleep patterns after the ICU stay. Conclusions: This multicenter study shows that pre‐existing diseases influence the HRQoL short‐ and long‐term after IC, and it must be accounted for when HRQoL and outcome after IC are studied. Approximately, 50% of the decline in HRQoL for the ICU patients could be explained by pre‐existing diseases. Future research needs to focus on the remaining factors of importance for the total HRQoL impairment for these patients.