| 1411. |
- Vogt, Hartmut
(author)
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Early life factors and the long-term development of asthma
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Asthma, a huge burden on millions of individuals worldwide, is one of the most important public health issues in many countries. As genetic and environmental factors interact, asthma may be programmed very early in life, perhaps even in utero.The aim of this thesis was to assess the impact of gestational age, cord blood immunoglobulin E (IgE), a family history of asthma, migration, and pertussis immunization in early life on the development of asthma in child and adult populations.As a proxy for asthma disease, dispensed asthma medication was used as the main outcome variable based on data from the Swedish Prescribed Drug Register. Data from other national registers were used to control for confounders. Three of our studies were based on national cohorts, and one on a local birth cohort that was initiated in 1974–75.Gestational age had an inverse dose-response relationship with dispensed asthma medication in 6– to 19-year-olds. Odds ratios for dispensed asthma medication increased with degree of prematurity compared with children born in term. Furthermore, asthma medication was more likely to be dispensed among children and adolescents born early term after 37–38 weeks’ gestation than among those at the same age who were born in term.Elevated cord blood IgE and a family history of asthma in infancy were associated with a two- to threefold increased likelihood of dispensed asthma medication and self-reported allergen-induced respiratory symptoms at the age of 32–34 years, but the predictive power was poor.Age at migration had an inverse dose-response relationship with dispensed asthma medication at the age of 6–25 years in adoptees and foreign-born children with foreign-born parents. International adoptees and children born in Sweden to foreign-born parents had three- to fourfold higher rates of asthma medication compared with foreign-born children who were raised by their foreign-born birth parents.No association was found between pertussis immunization in early infancy and dispensed asthma medication in 15-year-olds. The type of vaccine or vaccine schedule did not affect the outcome.Fetal life is a vulnerable period. This thesis strengthens the evidence that every week of gestation is important for lung maturation. Cord blood IgE, however, did not predict the risk of asthma in adults. Furthermore, the study of migrating populations demonstrated that environmental changes at any age during childhood may affect the risk of asthma. Another, important public health message from this thesis is that vaccination against pertussis in early childhood can be considered safe with respect to the long-term development of asthma.
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| 1412. |
- Vorkapić, Emina, 1987-
(author)
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Targeting vascular remodeling in abdominal aortic aneurysm : To identify novel treatment strategies and drug candidates
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Abdominal aortic aneurysm (AAA) is a degenerative weakening of the aortic wall, mainly affecting elderly men with a prevalence of 4.4-7.7 %. AAA is characterized by medial and adventitial inflammatory cell infiltration associated with vascular remodeling of the extracellular matrix proteins such as collagen and elastin and with phenotypic modulation and loss of vascular smooth muscle cells (VSMCs). Although much research has been performed, the precise cellular and molecular pathways behind these processes are still poorly understood. The overall aim of this thesis was to target signaling pathways that affect vascular remodeling of AAA to potentially identify novel strategies and drug candidates for future treatment of aneurysmal diseases. In order to develop our understanding of the pathophysiology of AAA, we used the angiotensin (Ang) II-induced AAA animal model and human biopsies taken at end-stage of disease to recapitulate key aspects of disease formation.Innate immune receptors such as toll-like receptors (TLRs) are known to regulate immunological processes leading to the formation and progression of vascular disease including AAA. In paper I, we aimed to investigate the role of TLR signaling under the control of the TRIF adaptor protein in the formation of AAA. Human, aneurysmal aortas displayed increased expression of TLR3 and TLR4 in surface of macrophages and T lymphocytes. AngII-induced aneurysm formation was attenuated in mice lacking the Trif gene (ApoE-/-Triʃ-/-), and these knockout mice presented with a more intact medial layer together with a reduced inflammatory response by macrophages and T lymphocytes and reduced levels of pro-inflammatory cytokines, chemokines, and proteases. Our results suggest an involvement of TRIF in the pathophysiology of AAA.Current management of AAA fully depends on imaging and surgical techniques, and drug-based therapies are still mostly ineffective. In paper II, we aimed to investigate the potential protective role of the tyrosine kinase inhibitor imatinib on the molecular mechanism involved in AAA formation. In AngII-infused ApoE-/-mice, 10 mg/kg imatinib per day affected several key features important in aneurysmal formation, including preservation of the medial layer of the VSMCs, reduced infiltrations of CD3ε-positive T lymphocytes, and reduced gene expression of mast cell chymase, resulting in decreased aortic diameter and vessel wall thickness. These results highlight the importance of the tyrosine kinase inhibitor imatinib as a potential drug in the treatment of pathological vascular inflammation and remodeling in conditions such as AAA.In paper III, we aimed to investigate the role of adiponectin in experimentally induced AAA formation in mice. In mice with elevated adiponectin levels, AAA development was inhibited, and this was associated with reduced inflammatory cell infiltration, reduced medial degeneration of VSMCs and of elastin in the aortic vessel wall together with an improved systemic cytokine profile and the attenuation of periaortic adipose tissue (PVAT) inflammation. These results support the protective effect of adiponectin in the remodeling occurring in the aortic wall and in the prevention of AAA.In paper IV, we performed a descriptive study investigating the composition of PVAT adjacent to the aneurysmal aorta. We used immunohistochemistry to identify neutrophils, macrophages, mast cells, and T lymphocytes surrounding necrotic adipocytes in PVAT together with increased gene expression of IL-6 and cathepsin K and S. We also determined the concentrations of pro-inflammatory ceramides in PVAT and found an association to T lymphocytes. These results suggest that inflamed adipose tissue might be a source of proinflammatory cells and mediators that contribute to aortic wall degeneration.
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| 1413. |
- Vretenbrant Öberg, Karin, 1979-
(author)
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The role of platelet thrombin receptors PAR1 and PAR4 in platelet activation
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Platelets play a pivotal role in coagulation and haemostasis. Their most prominent task is to seal damaged blood vessels by the formation of a platelet plug at the damaged area. Once the injury is covered, platelets retract the coagulum to close the wound and allow the blood to flow freely in the vessel. Platelets are strongly activated by the essential enzyme thrombin, formed in the coagulation cascade. Activation of the platelet thrombin receptors PAR1 and PAR4 leads to shape change, secretion of granule content, and aggregation, all of which can be accomplished by each receptor individually. However more and more findings indicate that there are differences between the receptors and that they have different physiological functions. This thesis presents studies performed to elucidate the relative role of PAR1 and PAR4 in platelet activation and coagulation. We have studied the effects on platelet activation and coagulation, and revealed a possible physiological role for PAR4 in the stabilisation of the coagulum. We also investigated the relative role of PAR1 and PAR4 in the cross-talk between thrombin and epinephrine with and without inhibition of COX-1. We demonstrated that PAR4 interacts with adrenergic receptors and causes an aggregation of platelets dependent on released ATP and its receptor P2X1, thereby circumventing the inhibition by aspirin. Not only is this an interesting specific role for PAR4, but it may also be of clinical importance considering that COX-1 inhibition is the most common treatment for patients with cardiovascular disease to prevent thrombosis. We show that the number of PAR1 receptors varied between donors and that this variation was correlated to the response on receptor activation. The number of PAR1 receptors on the platelet surface was decreased after PAR1 stimulation but increased after stimulation of other receptors. In a final attempt to elucidate the nature of PAR1 and PAR4 we used mathematics to evaluate the effect of co-stimulation of the receptors. We found a strong synergistic effect for both platelet activation and aggregation. This indicates that PAR1 and PAR4 interact in a yet unknown way to regulate or amplify the effect of each other rather than merely transmitting the incoming signal the same way.
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| 1414. |
- Vrethem, Magnus, 1955-
(author)
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Polyneuropathy associated with monoclonal gammopathy : A clinical, neurophysiological and immunological study
- 1994
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Doctoral thesis (other academic/artistic)abstract
- This thesis is based upon clinical, neurophysiological, and immunological studies of polyneuropathy (symmetrical impairment of sensory and motor nerve function) in patients with monoclonal gammopathies, that is, patients characterized by proliferation of a plasma-cell clone secreting homogeneous immWloglobulins (M-component), which in some patients has serum antibody reactivity against peripheral nerve myelin.The prevalence of clinical polyneuropathy in patients with monoclonal gammopathy (n=3) was 36%, and the prevalence of all forms of polyneuropathy including patients with neurophysiological signs only andpatients with probable polyneuropathy (signs but no symptoms) was 58%. IgM isotype of the M-component was associated with a high risk of clinical polyneuropathy (5 of 6; 83%). 3 patients, all with a demyelinating polyneuropathy, had antibodies against peripheral nerve myelin. It is concluded that polyneuropathy is common in patients with monoclonal gammopathy, but that only some polyneuropathies are of the demyelinating type and associated with circulating antibodies against peripheral nerve myelin.Immunofixation was superior to plasma agarose electrophoresis in detecting M-components in patients investigated for polyneuropathy (n=83). The prevalence of M-components was 7% (3 of 42 patients without obvious associated disease). The prevalence of M-components in the subgroup of patients with demyelinating polyneuropathy was even higher (21 %). Hence, patients with polyneuropathy should be screened for Mcomponents by a sensitive technique, not only to reveal a possible pathogenetie factor, but also because of the possibility of successful immunosuppressive treatment in some of them.Antibodies against peripheral nerve myelin were also shown to occur in healthy blood donors (25 of255; 10%). Only 2 of them had clinical and neurophysiological evidence of mild polyneuropathy. Their antibodies were shown to react with several proteins in peripheral nerve myelin, in contrast to patients with monoclonal gammopathy and polyneuropathy whose antibodies reacted with low molecular weight glycoproteins (14-30 kDa) in peripheral nerve myelin. The study confirms previous findings of autoantibodies in healthy persons.A positive correlation emerged between the amount of antibodies against peripheral nerve myelin and the proportion of circulating B-1 lymphocytes, known to be responsible for autoantibody production, in patients with polyneuropathy associated with monoclonal gammopathy. The findings suggest that B-1 cells produce antimyelin antibodies and support the idea of an autoinunune mechanism for the pathogenesis of polyneuropathy in some patients.Soluble interleukin-2 receptor (siL-2R) is secreted by activated T cells, and was elevated in 7 of 19 patients with monoclonal gammopathy and demyelinating polyneuropathy, as compared to 2 of 19 patients withmonoclonal ganuuopathy without polyneuropathy and in 1 of 15 healthy controls. The finding supports the hypothesis that T cells may have a regulatory role in the M-component production.Genomic typing for human leukocyte antigen (HLA) -DR and -DQ genes was done in 55 patients with monoclonal gammopathy. A polyneuropathy of demyelinating type was established in26 patients. Among these people an association was found with the presence of a tryptophan amino acid residue at position 9 of the DRB chain. This position is part of the first hypervariable region of the DRB chain, and may be of importance in detennining preferential peptide-binding capacity of the HLA-DR molecule. Anti-myelin-associated glycoprotein (MAG) antibodies were fmmd in 15 of 17 patients with an IgM M-component and demyelinating polyneuropathy (14 of these 15 people carried a tryptophan at position 9), supporting the pathogenctic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role ofT cell immunity in this condition.3 of 5 patients with monoclonal IgM and antibodies against peripheral nerve myelin responded to immunosuppressive treatment. In 3 patients the clinical response and the antibody concentration correlated, but in2 patients there was no clear correlation, because 1 patient improved despite increasing antibody concentration and 1 patient did hot improve despite a lowered antibody concentration. It is possible that mechanisms other than anti-peripheral-nerve myelin antibodies may contribute to the effect of treatment.In summary, it emerged that polyneuropathy is common in monoclonal gammopathy and that the method used to uncover an M-component is important. Both B cell and T cell responses may be involved in the pathogenesis, and a genetic susceptibility to develop polyneuropathy is possible. It is important to establish the diagnosis in these patients because immunosuppressive treatment may prove useful in some cases.
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| 1415. |
- Wadsby, Marie, 1954-
(author)
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Children of divorce and their parents
- 1993
-
Doctoral thesis (other academic/artistic)abstract
- Behavioural disturbances and symptoms of poor mental health in Swedish children were examined in conjunction with parental divorce and 2 years later, and in a group of immigrant and refugee children of divorced parents, on the basis of a semi-structured interview-instrument. The association between children's mental well-being and a number of background variables was analyzed. Children's self-image, charted by astandardized instrument, school achievement as assessed by final grades from compulsory school, and reactions to and experiences of divorce were studied. The reasons for the divorce, and differences in men's and women's experiences of changes a consequence of divorce were also studied. The study was based on a one-year-sample of divorcing couples and their young children, and 27 divorced irnmigranl/refugee families.The presence of behavioural disturbances and symptoms of poor mental health was similar in children of divorce and in children of intact homes, although Swedish boys <5 years of age at the time of the divorce emerged a vulnerable group two years following the event Compared to Swedish children of divorce, immigrant children and especially refugee children of divorce displayed poorer mental health. Children 7-12 years of age reacted strongest to the divorce compared to younger and older children. Parental psychiatric vulnerability alcohol abuse, and a heart-rending divorce were factors associated with children's mental well-being. Especially a heart-rending divorce was noted to be a crucial variable in predicting the mental well-being of young boys at the time of divorce.The self-image of children of divorce was similar to that of children of intact homes as assessed by standardized norms. Academic achievement was similar in' children of divorce and in children of intact homes.Children devoted more thoughts to the divorce than their parents had realized, and boys and young children accepted the divorce less than the parents believed. The results indicated a lack of information and communication about the divorce between children and parents.The divorce experience differed between men and women in several areas, especially with regard to the financial situation, relations with friends, work, physical health, mental well-being, and self-confidence, mostly favouring the women.The main conclusion of the study was that the mental health of children of divorce is similar to children of intact homes at the time of divorce and two years later.
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| 1416. |
- Wahlberg, Jeanette, 1969-
(author)
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Environmental determinants associated with Type 1 diabetes-related autoantibodies in children
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Background Type 1 diabetes is a severe disease, which affects children with potentially severe consequences. The global incidence of Type 1 diabetes is increasing rapidly especially in young children. Second to Finland, Sweden has the highest incidence of Type 1 diabetes in the world.The rapidly increasing incidence cannot be explained by a possible variability of the presence of risk genes in the population, but rather environmental factors.Therefore, environmental factors contributing to ß-cell auto immunity should be of importance for the process leading up to clinical Type I diabetes in genetically predisposed individuals. Those factors should preferably be revealed early in life. The aim of this thesis was to investigate a large population of Swedish children in order to identify environmental factors, which could contribute to the autoimmune reaction towards insulin-producing ß-cells.Material and methodsFamilies from the prospective population-based ABIS-project (All Babies in southeast Sweden) were studied. Blood samples from children were analysed at birth, one year and 2½ years of age for diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2A) and Glutamic Acid Decarboxylase (GAD). The parents completed questionnaires at birth, one year and 2½ years of age.Results Short breast-feeding period, early exposure to cow's milk formula and late introduction of gluten-containing foods as well as large consumption of cow's milk at the age of one year were all risk determinants for development of autoantibodies at 2½ years of age. Combined early introduction of cow's milk formula and late introduction of gluten-containing food increased the risk six times for acquiring persistent autoantibodies at 2½ years of age. Parenting stress and experiences of serious life events were associated with the induction of diabetes-related autoimmunity. Infections during pregnancy are related to diabetes-related autoantibodies in cord blood and at the age of one year.Allergic symptoms such as rash, wheezing, allergy against fur-bearing animals and food allergies implied a risk for development of diabetes-related autoantibodies. Autoantibodies in cord blood had disappeared at the age of one year, and can therefore not be used as a screening method to predict diabetes in the general population.ConclusionsNone of the examined risk factors alone can explain Type 1 diabetes-related autoimmunity; but early nutrition, parental stress and infections can contribute to the development of diabetes-related autoantibodies.Autoantibodies in cord blood cannot be used to predict later diabetes-related autoimmunity. Different aberrances in the immune system seem to co-exist in certain individuals.
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| 1417. |
- Waldemar, Annette, 1969-
(author)
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In-hospital family-witnessed adult resuscitation : Perspectives of patients, families and healthcare professionals
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Background Several international organizations recommend family-witnessed resuscitation (FWR) in hospitals, which means that the family should be offered to be present during resuscitation. These recommendations are based on research that shows that it is usually beneficial for the family to be present. The family can see that everything was done for the patient, they can say goodbye, they acknowledge that the patient passed away and the grieving process is facilitated. However, research has yet to examine how FWR affects the patient and family members who were present during the cardiac arrest and what it is like to live on with the shared experience. Healthcare professionals (HCPs) in general are sceptical of FWR, and current guidelines that recommend FWR have not made a significant im-pact in healthcare. HCPs believe that FWR could worsen the outcome for the patient and that the family could be psychologically damaged by being present during resuscitation.HCPs also express uncertainty about how to act during FWR, because they have not received education or training about FWR. There is a need for research concerning the outcomes of FWR in hospitalized adult patients. Research on the experiences, attitudes, and self-confidence of HCPs in Sweden in relation to FWR, as well as the shared experiences of patients and families, is lacking. There is also lack of research exploring whether an educational intervention can have a positive impact on attitudes and self-confidence among HCPs. Overall Aim The overall aim of this thesis was to describe the prevalence, processes, and outcomes of FWR; explore experiences and attitudes towards FWR among patients, families, and HCPs; and to further develop and test an educational intervention addressing HCP. Methods This thesis includes four studies, where the first study used a cross-sectional design (I), Study II was a retrospective observational cohort study, Study III was a qualitative study, and Study IV used a quasi-experimental design. The sample size ranged between 15-4846 participants across the studies. Data was collected through web surveys (I, IV), registers (II), and narrative face-to-face interviews (III). Descriptive and correlational statis-tics were used in the quantitative studies (I-II, IV) and interpretative phenomenological analysis (IPA) in the qualitative study (III). A 10-minute educational video was developed, pilot tested, and used as intervention in Study IV. The video was based on previous research covering the prevalence and outcome of FWR, attitudes among HCPs, patient and family experiences, and FWR guidelines. Results It was significantly more common that a family member was on site if the cardiac arrest occurred in acute settings such as emergency departments and intensive care units than in hospital wards (44% vs. 26%, p<0.001). In total, 395 patients (12 %) had family on site when the cardiac arrest occurred, in 186 of these cardiac arrests the family chose to witness resuscitation. (II). The mean time from initiation to termination of resuscitation was significantly longer if a family member was present (17.7 vs. 20.7 minutes, p=0.020) (II). There were no significant differences in survival rate between FWR and non-FWR, neither immediately after resuscitation (57% vs. 53%, p=0.291) nor in 30-day survival (35% vs. 29%, p=0.086) (II). HCPs reported a wide range of experiences regarding FWR (I, IV). More nurses (70%) than physicians (49%) expressed positive experiences in Study I, while in Study IV, the proportions were the opposite, with 52% of physicians and 33% of nurses reporting positive experiences. Regarding attitudes, the results from Study IV show a more positive attitude towards offering the family the opportunity to be with the patient during CPR compared to Study I. In Study IV, 77.1% of nurses and 58.1% of physicians reported a positive attitude towards FWR, while in Study I, 58.7% of nurses and 29.2% of physicians were positive. Performing defibrillation, administering drug therapies, and providing chest compressions during FWR were not considered to be a problem for either physicians or nurses. Nevertheless, being able to identify family members who demonstrate appropriate coping behaviours was more difficult, and 27% of nurses and 37% of physicians reported that they had no confidence in performing this task. Furthermore, 52.7% of nurses and 69.4% of physicians were not comfortable encouraging family members to talk to the patient during resuscitation (IV). In Study I, none of the included hospitals reported having local guidelines about FWR, while 18.6% reported that they had guidelines seven years later when Study IV was per-formed. The results suggest that the educational intervention had a positive influence on HCPs’ self-confidence during FWR (3.83±0.70 to 4.02±0.70, p<0.001) and their attitudes towards FWR (3.38±0.49 to 3.62±0.48, p<0.001) (IV). Patients and families describe powerlessness in the face of life's fragility, but also faith in life after experiencing and surviving a sudden cardiac arrest together. Even though the participants felt exposed and vulnerable in the care relationship and lacked a sense of control and continuity, they had hope and re-evaluated life, lived in the moment and saw the value in everyday life. The love they felt for people who were important to them and the gratitude for life increased after the cardiac arrest. The desire for freedom and independence also increased (III). Conclusion Surviving as well as witnessing an in-hospital cardiac arrest is a critical event making patients and family members vulnerable. To meet their needs, HCPs should routinely invite the family to witness resuscitation if it is deemed to be safe. HCPs need to show compassion and evaluate how family members are coping during the process and provide support and in-formation during and after resuscitation. Processes and outcomes do not seem to be negatively affected by FWR, even though there is some resistance to FWR among HCPs. These obstacles must be considered when planning for the implementation of FWR in daily practice. A short online educational video can be a way to improve the self-confidence and attitudes towards FWR among HCPs. This will likely result in increased compliance with national and local guidelines that recommend FWR.
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| 1418. |
- Waldén, Markus, 1975-
(author)
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Epidemiology of injuries in elite football
- 2007
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Doctoral thesis (other academic/artistic)abstract
- The purpose of this thesis was to study the injury characteristics in elite football, and risk factors for injury with special emphasis on anterior cruciate ligament injury. All five papers followed a prospective design using a standardised methodology. Individual training and match exposure was recorded for all players participating as well as all injuries resulting in time loss. Severe injury was defined as absence from play longer than 4 weeks.In Paper I, all 14 teams in the Swedish men’s elite league were studied during the 2001 season. In this paper, all tissue damage regardless of subsequent time loss was also recorded. There were no differences in injury incidence between the two injury definitions during match play (27.2 vs. 25.9 injuries per 1000 hours, p=0.66) or training (5.7 vs. 5.2 injuries per 1000 hours, p=0.65). Significantly higher injury incidences for training injury, overuse injury and re-injury were found during the pre-season compared to the competitive season. Thigh strain was the single most common injury (14%).In Paper II, 8% of all players in the Swedish men’s elite league 2001 had a history of previous ACL injury at the start of the study period. These players had a higher incidence of new knee injury during the season than players without previous ACL injury (4.2 vs. 1.0 injuries per 1000 hours, p=0.02). The higher incidence of new knee injury was seen both when using the player (relative risk 3.4, 95% CI 1.8-6.3) and the knee (relative risk 4.5, 95% CI 2.3-8.8) as the unit of analysis.In Paper III, eleven clubs in the men’s elite leagues of five European countries were studied during the 2001-2002 season. The incidence of match injury was higher for the English and Dutch teams compared to the Mediterranean teams (41.8 vs. 24.0 injuries per 1000 hours, p=0.008) as well as the incidence of severe injury (2.0 vs. 1.1 injuries per 1000 hours, p=0.04). Players having international duty had a higher match exposure (42 vs. 28 matches, p<0.001), but a tendency to a lower training injury incidence (4.1 vs. 6.2 injuries per 1000 hours, p=0.051). Thigh strain was the most common injury (16%) with posterior strains being more frequent than anterior ones (67 vs. 36, p<0.0001).In Paper IV, the national teams of all 32 countries that qualified for the men’s European Championship 2004, the women’s European Championship 2005 and the men’s Under-19 European Championship 2005 were studied during the tournaments. There were no differences in match and training injury incidences between the championships. Teams eliminated after the group stage in the women’s championship had a significantly higher match injury incidence compared to teams going to the semi-finals (65.4 vs. 5.0 injuries per 1000 hours, p=0.02). Non-contact mechanisms were ascribed for 41% of the match injuries and these injuries were more common in the second half.In Paper V, all 12 clubs in the Swedish women’s elite league and 11 of 14 clubs in the men’s elite league were studied during the 2005 season. The prevalence of a history of previous ACL injury at the start of the study was three times higher among the female players (15% vs. 5%, p=0.0002). During the season, 16 new ACL injuries were recorded. There was a tendency to a lower mean age at injury among the women (20 vs. 24 years, p=0.069). Adjusted for age, no gender-related difference in the incidence of ACL injury was seen (relative risk 0.99, 95% CI 0.37-2.6). Age was associated with ACL injury incidence in women where the risk decreased by 24% for each year increase in age (relative risk 0.76, 95% CI 0.59-0.96).
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| 1419. |
- Waldréus, Nana
(author)
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Thirst in Patients with Heart Failure : Description of thirst dimensions and associated factors with thirst
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Introduction: Nurses and other health care professionals meet patients with heart failure (HF) who report they are thirsty. Thirst is described by the patients as a concern, and it is distressing. Currently there are no standardized procedures to identify patients with increased thirst or to help a patient to manage troublesome thirst and research in the area of thirst is scarce. In order to prevent and relieve troublesome thirst more knowledge is needed on how thirst is experienced and what factors cause increased thirst.Aim: The aim of this thesis was to describe the thirst experience of patients with HF and describe the relationship of thirst with physiologic, psychologic and situational factors. The goal was to contribute to the improvement of the care by identifying needs and possible approaches to prevent and relieve thirst in patients with HF.Methods: The studies in this thesis used a cross-sectional design (Study I) and prospective observational designs (II-IV). Studies include data from patients with HF who were admitted to the emergency department for deterioration in HF (I, IV) or visited an outpatient HF clinic for worsening of HF symptoms (III); others were patients who were following up after HF hospitalization (II), and patients with no HF diagnosis who sought care at the emergency department for other illness (I). Patients completed questionnaires on thirst intensity, thirst distress, HF self-care behaviour, feeling depressive and feeling anxious. Data on sociodemographic, clinical characteristics, pharmacological treatment and prescribed fluid restriction were retrieved from hospital medical records and by asking the patients. Data were also collected from blood, urine and saliva samples to measure biological markers of dehydration, HF severity and stress.Results: Thirst was prevalent in 1 out of 5 patients (II) and 63% of patients with worsening of HF symptoms experienced moderate to severe thirst distress at hospital admission (IV). Patients at an outpatient HF clinic who reported thirst at the first visit were more often thirsty at the follow-up visits compared to patients who did not report thirst at the first visit (II). Thirst intensity was significantly higher in patients hospitalized with decompensated HF compared to patients with no HF (median 75 vs. 25 mm, visual analogue scale [VAS] 0-100 mm; P < 0.001) (I). During optimization of pharmacological treatment of HF, thirst intensity increased in 67% of the patients. Thirst intensity increased significantly more in patients in the high thirst intensity group compared to patients in the low thirst intensity group (median +18 mm vs. -3 mm; P < 0.001) (III). Patients who were admitted to the hospital with high thirst distress continued to have high thirst distress over time (IV). A large number of patients were bothered by thirst and feeling dry in the mouth when they were thirsty (III, IV). Patients with a fluid restriction had high thirst distress over time and patients who were feeling depressed had high thirst intensity over time (IV). Thirst was associated with fluid restriction (III-IV), a higher serum urea (IIIII), and depressive symptoms (II).Conclusions: A considerable amount of patients with HF experiences thirst intensity and thirst distress. Patients who reported thirst at the first follow-up more often had thirst at the subsequent follow-ups. The most important factors related to thirst intensity or thirst distress were a fluid restriction, a higher plasma urea, and depressive symptoms. Nurses should ask patients with HF if they are thirsty and measure the thirst intensity and thirst distress, and ask if thirst is bothering them. Each patient should be critically evaluated if a fluid restriction really is needed, if the patient might be dehydrated or needs to be treated for depression.
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| 1420. |
- Walfridsson, Ulla, 1957-
(author)
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Assessing Symptom Burden and Health-Related Quality of Life in patients living with arrhythmia and ASTA : Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Background: Health-Related Quality of Life (HRQOL) can be negatively affected in patients living with arrhythmias and many patients experience a pronounced symptom burden. The arrhythmia can cause both uncertainty and limitations, including interference with work, reluctance to perform and plan for leisure activities and leading to self-imposed restrictions in daily life situations. There are patients striving to find strategies to manage the arrhythmia and for some this can become the focus in their lives. Treatment options are often a choice between pharmaceuticals and radiofrequency ablation (RFA) where RFA is an option for many arrhythmia-patients to be cured. In the care of arrhythmia-patients it is of great importance to combine objective examinations with patient-reported outcomes (PROs) to achieve patient’s own experiences of treatment efficacy and arrhythmias interference in daily life situations.Aims: The overall aims of this thesis were to assess symptom burden and HRQOL in patients with arrhythmias and to develop and validate an arrhythmia-specific questionnaire, suitable for most arrhythmia-patients.Design and Methods: Studies I and II were single-centre studies including patients referred for RFA, with two different arrhythmia diagnoses. Assessments of patient-reported outcomes (PROs) concerning HRQOL were performed using two questionnaires, SF-36 and EQ-5D (I-II). Further, patients were asked some disease-specific questions (I). Study I describes assessments before the RFA treatment and Study II the follow-up assessments at three and twelve months after RFA. Patients’ scoring of HRQOL was compared to age and gender matched reference groups before and after RFA (I-II). Studies III and IV describe the development and validation of a disease-specific questionnaire ASTA (Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia) assessing symptom burden and HRQOL. Studies III and IV were multicentre studies. Patients planned for DC-conversion, AF patients seeking emergency care and those with different forms of arrhythmias referred for RFA were included.Results: Patients scored significantly lower HRQOL in seven of SF-36’s eight scales compared to the age and gender matched reference groups before RFA treatment. Frequent arrhythmia attacks had a great negative impact on HRQOL, and female gender and older age were factors contributing to worse HRQOL (I). Treatment with RFA restored the patients’ HRQOL. Most positive effects were seen at three months follow-up. One year after treatment patients and the matched reference group scored their HRQOL to a similar level, assessed with SF-36 and EQ-5D index (II). The validated ASTA questionnaire was found to have good psychometric properties. Construct validity was confirmed with sufficient levels of item-total correlations in the ASTA symptom burden scale and HRQOL scales. The dimensionality of the ASTA HRQOL scale was established with confirmatory factor analysis, supporting a physical and a mental subscale. The internal consistency, demonstrated with Cronbach’s alpha (α), was satisfactory for the ASTA symptom burden scale and the ASTA HRQOL scales, varying from α 0.79 to α 0.91 (III-IV).Conclusions and clinical implications: The studies in this thesis confirmed how negatively affected the arrhythmia-patients can be with a pronounced symptom burden and impaired HRQOL. Treatment with RFA was demonstrated to restore the patients HRQOL to an equal level of that of the matched reference group. PROs are important to take into consideration in the care of arrhythmia-patients, to achieve the patients’ subjective experiences of their daily life situation.To the best of our knowledge ASTA is the first arrhythmia-specific questionnaire assessing symptom burden and HRQOL, suitable for most arrhythmia forms. The newly validated ASTA questionnaire can be an important contribution to assessment of PROs in arrhythmia-patients.
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