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- Henningsson, Anna J, 1972-
(författare)
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Clinical, epidemiological and immunological aspects of Lyme borreliosis with special focus on the role of the complement system
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere. The infection is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and it is transmitted to humans by ticks. LB is associated with several clinical manifestations, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common inEurope. The course of the disease is usually benign, but can vary between individuals. The underlying pathogenic mechanisms are not fully understood, but the prognosis is probably determined by a complex interplay between the bacteria and the host’s immune response. Previous studies have indicated that a strong initial T helper (Th) 1-response followed by a Th2 response is beneficial for the clinical outcome in LB.The aims of this thesis were to follow the incidence of NB inJönköping County,Sweden, over time, to search for clinical and laboratory markers associated with the risk of developing long-lasting post-treatment symptoms, and to explore the role of the complement system as well as the relative balance between Th-associated cytokine/chemokine responses in LB.The number of NB cases, diagnosed by cerebrospinal fluid (CSF) analysis, increased from 5 to 10/100,000 inhabitants/year in Jönköping County during 2000-2005. Post-treatment symptoms persisting more than 6 months occurred in 13 %, and were associated with higher age, longer-lasting symptoms prior to treatment, higher levels of Borrelia-specific IgG in CSF, and reported symptoms of radiculitis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients.Complement activation occurred both locally in the skin in EM and in CSF of NB patients. However, no activation could be detected in blood in NB patients. Elevated levels of C1q, C4 and C3a in CSF, along with correlation between C1q and C3a levels, suggest complement activation via the classical pathway locally in the central nervous system in NB. In vitro experiments with two clinical Borrelia isolates revealed that B. garinii LU59 induced higher complement activation in human plasma compared to B. afzelii K78 that recruited more of complement regulator factor H. To elucidate the role of complement in the phagocytosis process, experiments were performed using whole blood from healthy donors incubated with fluorescence-labelled spirochetes and different complement inhibitors. The results illustrated a central role of complement for phagocytosis of Borrelia spirochetes.We also studied the relative contribution of different Th-associated cytokines/chemokine responses in NB. The results support the notion that early NB is dominated by a Th1 response, eventually accompanied by a Th2 response. IL-17A was increased in CSF in half of the patients with confirmed NB, suggesting a hitherto unknown role of Th17 in NB.In conclusion, the risk of developing long-lasting post-treatment symptoms tend to increase mainly with age and duration of symptoms prior to treatment in NB. The complement system seems to play an important role in host defence to recognize and kill Borrelia spirochetes. However, complement activation in inappropriate sites or to an excessive degree may cause tissue damage, and therefore, the role of complement in relation to disease course needs to be studied further. Likewise, the role of Th17 in LB pathogenesis and host defence should be further evaluated in prospective studies.
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| 2. |
- Wissendorff Ekdahl, Anne
(författare)
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Frail and Elderly Hospital Patients : The Challenge of Participation in Medical Decision Making
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In research, patient participation in medical decision-making has been shown to be associated with higher patient satisfaction and improvement of treatment outcomes. But when it comes to patient participation when being old and frail there are pitfalls and the research in this area is sparse.The aim of this thesis is to explore participation in medical decision making of the frail elderly patient in hospital from the perspectives of patients themselves and the health care staff. In this thesis frail, elderly patients is defined as individuals 75 years old or older, who during the past 12 months have received inpatient hospital care three or more times and who have three or more diagnoses in three or more diagnostic groups according to the classification system ICD-10.The participants were frail patients’ in hospital or newly discharged and it was health care personnel working with frail elderly patients. In three of the studies the method was mainly qualitative (Paper I, III, IV) and in one (Paper II) quantitative. The qualitative methods were one-to-one tape-recorded interviews of 25 patients (Paper I and IV), 18 personnel (III and IV), 5 focus group interviews of physicians (Paper III) and 26 days of observations in hospital wards (IV). Chosen methodologies of analysis were content analysis and Grounded Theory. The quantitative study (II) was a cross-sectional survey using telephone interviews with patients (n= 156). This material was descriptively analysed and examined using weighted kappa statistics.Results: The results reported in Paper II show that elderly patients generally want to participate more in medical decision making than they do, though preferences for degree of participation are highly individualized – both findings important to consider in clinical practice.According to the patients important key concepts of patient participation in medical decision making are to be listened to and to be informed (Paper I). The main reasons for not being able to participate included having many illnesses and generally, overall bad medical condition (Paper II). Also, cited as a problem was difficulty in understanding medical information, for example when given by a foreign-speaking physician (Paper I, II and IV). Frail, elderly patients complained that they were less informed than was their preference (Paper I, II and IV).Moderate agreement was obtained between patient’s preferred and actual roles in medical decision making. Patients often expressed gratitude and confidence in their health care (Paper I and IV), but also, sympathy for stressed health care personnel who had so much to do.The frail elderly patients do sometimes feel like a burden to the health care (Paper I and IV). The professionals gave expressions of trying to avoid taking care of frail elderly patients and at the same time expressions of frustration and bad conscience not being able to take good care of them due to lack of time and lack of beds (Paper III, IV). Especially the physicians felt they were trapped between the needs of the patients’ and the remunerations system rewarding time-constricted health care production (number of investigations, operations, easy accessibility) – not a time-consuming holistic view on all illnesses and medications including communication with the patients and all caregivers involved (Paper III).Both patients and the professionals perceive the hospital as some kind of “institution of power”, difficult to challenge, and the decisions of which one has to accept.Conclusion: In this thesis there are shown a number of challenges to participation in medical decision making by frail, elderly patients, which thus limits quality of care for this patient group. Health care is revealed as not well adapted to meet these patients’ complex needs. A model is presented that explains how the organisation of health care, and the reimbursement system, does not facilitate a holistic view. The health care professionals appear to adapt to the organisation and the remuneration system, which leads to practices, such as, rapid discharges and a tendency to examine the patient for only one or a few problems. Finally a suggestion for a model to improve care of frail elderly patients is presented. This model includes the need of more hospital wards being able to work with a holistic view, better skills in gerontology and geriatrics and a more adapted remuneration system for the frail, elderly patients.
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