| 1. |
- Andersson, Jonas, 1977-
(författare)
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Inflammation and lifestyle in cardiovascular medicine
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future. The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome. Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later. In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up. In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage. A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome. In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.
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| 2. |
- Brännström, Margareta, 1957-
(författare)
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Ett liv i berg och dalbana : innebörder av att leva med svår kronisk hjärtsvikt i palliativ avancerad hemsjukvård utifrån patienters, närståendes och sjuksköterskors berättelser
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall purpose of this thesis is to illuminate meanings of living with severe chronic heart failure (CHF) in palliative advanced home care (PAHC) as disclosed through patients’, close relatives’ and nurses’ narratives. This thesis comprises four papers that illuminate the phenomenon from various perspectives and with different focus. In paper I four patients with severe CHF in PAHC were interviewed. In paper II three of their close relatives were interviewed. In paper III one man and his wife in PAHC were interviewed at 3-5 month intervals over a 4.5-years period. In paper IV 11 nurses in PAHC were interviewed. In all papers narrative interviews were conducted and the text was interpreted using a phenomenological-hermeneutic method. The result shows that meanings of living with severe CHF in PAHC is to be ‘knocking on death’s door’ yet surviving. This means never knowing what to expect of tomorrow as one suffers from a complex array of unpredictable, interwoven symptoms. The course of the illness forces sufferer to ride a symbolical ‘roller coaster’, an ongoing oscillation between ‘ups and downs’. Being offered a safety belt in the ‘roller coaster’ by the PAHC team means feelings of safety (I). Meanings of being a close relative of a person with severe CHF in PAHC is to be following the life- threatening ups and downs that the ill person goes through. It is like being a fellow passenger on the ‘roller coaster’ ride that is their loved one’s disease, with burdensome responsibility for easing the ‘downs’ and supporting the ‘ups’. This means being on primary call, always on standby to mediate security and pleasure. In the deepest downs it is also to call for the back-up call i.e. the PAHC team (II). Meanings of living the ‘ups and downs’ over time is being captive in a roller-coaster ride, side by side, with the ‘ups and downs’ caused by the illness. Living close to death is inescapable when recurrent periods of deepest ‘downs’ force one to face that one’s life together is coming to an end. The relationship between the spouses is severely tested but seems to withstand the strain and meaning is found in togetherness in life. Sharing the safety belt on the ‘roller coaster’, offered by the PAHC team, evokes feelings of security. However, the safety belt is adjusted to the man with severe CHF leaving the wife partly without comfort and at times uncertain, especially in the deepest ‘downs’ (III). Meanings of being a palliative nurse for patients with severe CHF in PAHC is being firmly rooted and guided by the values of palliative culture. Being a facilitator for the patient with CHF to live his/her everydaylife in the best way possible is difficult, challenging but overall positive. The nurses get into a tight corner when palliative culture values clash and do not correspond to nurses’ interpretation of what is good for the patient with severe CHF. There is a limit to nurses’ pliability to patients’ and close relatives’ will, as they are strongly convinced that resuscitation is not an option. Nurses have already made up their mind about that they do not perform heart- lung resuscitation (IV). The comprehensive understanding is that meanings of living with severe CHF in PAHC is being captive in a ‘roller-coaster’ life with varying periods between unpredictable improvement and deterioration of the body, for the rest of life. Living with the unpredictable, deteriorated body means to oscillate between enduring the suffering in ‘downs’ and enjoying life in ‘ups’ (I-III). Living with death so close over and over again i.e. being in a limit situation evokes feelings of uncertainty (I-IV) and confidence (I-III). Being positive dependent on PAHC facilitates a life as normal as possible in togetherness at home (I-IV). The comprehensive understanding of the four papers (I-IV) are discussed in the light of a theoretical framework from the German psychiatrist and philosopher Karl Jaspers thoughts about limit situation, the Danish philosopher K.E Lögstrup thoughts about the ethical demand, palliative theories and relevant empirical studies.
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| 3. |
- Hedman, Mante, 1960-
(författare)
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The community hospital model in northern Sweden
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Rural community hospitals (CHs) are vital in delivering healthcare services in sparsely populated regions such as northern Sweden. In Sweden these facilities act as primary care units, staffed by general practitioners (GPs), nurses, and other healthcare professionals. They provide hospital beds, emergency care, and basic diagnostics. The CH model, with GPs responsible for hospital care has not been studied earlier in Sweden. Aims: This thesis aimed to examine the role and practices of the Swedish rural CH model within the healthcare system and the local community. Furthermore, to investigate the perspectives of rural doctors in Sweden and New Zealand (NZ) working within their respective hospital models. Specific aims: To characterise patients admitted to hospitals in Norrbotten and Västerbotten Regions and to compare hospitalisations at rural community hospitals and general hospitals (Study I)To describe registered care measures carried out in rural community hospitals during episodes of hospital care for patients with heart failure, in comparison with a general hospital (Study II)To explore rural hospital doctors’ experiences of providing care in rural hospitals in Southern New Zealand (Study III)To explore rural general practitioners’ experiences of providing care in rural community hospitals in northern Sweden (Study IV) Methods and results: Four original papers form the basis of this thesis. In study I, hospital register data from Norr- and Västerbotten Regions were analysed, focusing on hospital admissions of patients enrolled at CHs 2010-2014. We compared CH admissions with general hospital admissions, examining factors such as age, sex, and diagnoses. CH patients were older than those in general hospitals (median age 80 vs. 68 years), and women had a higher likelihood of admission to CHs compared to men. Common diagnoses in the elderly, such as heart failure and pneumonia were more likely admitted to CHs than to general hospitals. Study II utilized hospital register data from Region Västerbotten to describe registered care measures carried out in rural CHs during episodes of hospital care for patients with heart failure 2015-2019, in comparison with a general hospital. CHs showed documentations by fewer individual doctors, more frequent nursing documentation, and fewer blood tests compared to general hospitals. Radiology, including echocardiography, was performed in general hospitals only but in a minority of cases. Documentation by physiotherapists, occupational therapists, and dietitians was limited in both hospital models.Studies III and IV involved interviews with rural hospital (RH) doctors in New Zealand (NZ), and rural GPs in northern Sweden, respectively, to explore the role of their RH/CH. In both countries, doctors emphasised advantages with proximity and holistic, patient-centred care for elderly, multimorbid, and end-of-life patients. Their RHs/CHs were described to play a central role in rural patients' healthcare journeys, utilizing small, multidisciplinary teams and collaborating with general hospitals and municipal caregivers. Reported challenges for doctors in RHs and CHs included limited resources and inexperience in handling life-threatening, rare cases, and ethical dilemmas unique to rural practice. Despite this, RH doctors considered RH patient safety similar or better than that in general hospitals. CH doctors prompted the idea of expanding the CH model to urban areas. Conclusion: We conclude that CHs admit elderly and multimorbid patients elsewhere common in general hospitals. Care for patients with heart failure at CHs showed more nursing notes, greater doctor continuity, and less biomedical examinations. Our results suggest potential for further development in the multidisciplinary care in both hospital models. Rural generalist doctors in Sweden and NZ emphasise the central role of CHs/RHs, their proximity to patients, and their holistic, generalist approach, and they suggest advantages in the RH/CH care for the elderly compared to general hospitals. In Sweden, the importance of relational continuity was stressed, as rural GPs are familiar with their CH patients from primary care.
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| 4. |
- Lind, Marcus, 1975-
(författare)
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Determinants of adverse events during oral anticoagulant treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.
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| 5. |
- Olofsson, Mona, 1952-
(författare)
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Heart failure in elderly with focus on diagnosis and prognosis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients older than 75 years with heart failure (HF) are at increased risk for mortality and hospital admissions. Echocardiography and brain natriuretic peptides (BNP, NTproBNP) are important diagnostic tools but sparsely evaluated in elderly PHC patients. Aims: Validate the clinical diagnosis of HF, investigate the types of HF and underlying cardiovascular disorders with focus on sex and age differences. Explore the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of BNP and NT-proBNP in patients with systolic HF. Study the associations of HF or NTproBNP on all-cause and cardiovascular mortality. Study the prognostic value of different biomarkers and HF, on all-cause and cardiovascular hospitalizations. Methods: Patients with suspected HF were recruited from one selected PHC and registered on a prespecified record and referred for an echocardiographic examination and a final cardiologist consultation. Blood samples for natriuretic peptides were stored frozen at – 70° C. Death certificates were used to register all-cause mortality and cardiovascular mortality. To register hospitalisations, medical records were used and classification was defined according to ICD-10. Results The GPs identified 121 women and 49 men with suspected HF of whom 39% (51 women and 16 men) were above 80 years. Myocardial infarction (OR:4,3 CL: 1,8-10,6) hypertension (OR:3,4 CI:1,6-6,9) atrial fibrillation (OR:2,8 CL:1,0-7,9) predicted a confirmed diagnosis of HF. Confirmed HF was verified in 45% of the patients and was significantly more common in men than women (p=0,02). The best NPV was 88 % for NT-proBNP (200 ng/L) and 87 % for BNP (20 pg/ml). Age and male gender were independently associated with higher levels of NT-proBNP. During the 10-year follow up, 71 out of 144 patients died. In univariate Cox regression analysis, significant associations were found for overall HF (hazard ratio [HR]: 1.86; 95% confidence interval [CI]:1.15- 3.01), isolated systolic HF (HR:1.95; 95% CI:1.06-3.61), and combined (systolic and diastolic) HF (HR:3.28; 95% CI:1.74-6.14) with all-cause mortality, but not for isolated diastolic HF. In multivariable analysis, age (HR: 1.11; 95% CI: 1.06-1.17), kidney dysfunction (HR:1.91; 95% CI:1.11- 3.29), smoking (HR:3.70; 95% CI:2.02-6.77), and NTproBNP (HR:1.01; 95% CI:1.00-1.02), but not any type of HF, significantly predicted all-cause mortality. During ten years, 136 (80%) patients were hospitalised with 660 and 207 for all-cause and cardiovascular hospitalisations, respectively. Age (OR:1.1; 95% CI:1.01-1.15) and underlying heart disease (OR:3.5; 95% CI:1.00-11.89), significantly predicted all-cause hospitalisation. Overall HF (HR:1.8; 95% CI:1.06-2.94) significantly predicted time to first all-cause hospitalisations. For cardiovascular hospitalisations age (OR:1.1;95%CI:1.01-1.12), underlying heart disease (OR:3.4;95%CI:1.04-11.40) and NTproBNP ≥800 ng/L (OR:4,3;95%CI:1.5-12.50) were significant predictors. Conclusion: A confirmed diagnosis of HF was present in 45% of the patients. NPV was high, but not as high as in younger patients with HF. Patients with systolic HF had a higher mortality than patients with diastolic HF compared to patients with no HF. Patients with combined HF were at even higher risk for all-cause mortality and cardiovascular mortality. Age, kidney dysfunction, NTproBNP and smoking predicted mortality. Age and underlying heart diseases were predictors for all-cause hospitalisations and together with NTproBNP they also predicted cardiovascular hospitalisations.
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| 6. |
- Rautio, Aslak, 1962-
(författare)
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Diabetes Mellitus and Cardiovascular Risk : epidemiology, etiology and intervention
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Framingham Study from 1988 showed a heavy impact of diabetes mellitus (DM) on the risk and prognosis of cardiovascular disease (CVD). Several other studies have confirmed that DM is an independent risk factor for coronary heart disease (CHD) and that patients with DM have a poor prognosis. However, the strength of DM as a risk factor is debated. Some studies indicate that DM, as a risk factor for a coronary event, is comparable to already known or established CHD. Also, mechanisms of how diabetes increases the CVD risk are under intensive research. A novel risk factor such as altered fibrinolysis is one of the potential mechanisms explaining the heavy cardiovascular burden in diabetes. Hypofibrinolytic changes can be seen in individuals with metabolic syndrome, insulin resistance, and obesity as well as in patients with manifest diabetes or manifest CHD.Methods: This dissertation is divided in three parts; epidemiological, etiological and interventional. Papers I and II are epidemiological, population based retrospective studies which compare time trends in myocardial infarction and stroke morbidity and mortality between patients with or without diabetes. Papers III and IV have an etiological approach to the fibrinolytic system and CVD risk both in patients with or without diabetes. Paper V is the interventional part of this thesis studying if intensive insulin treatment can improve fibrinolysis in patients with high CVD risk.Results: The incidence and mortality from myocardial infarction and stroke have declined in the counties of Västerbotten and Norrbotten in Northern Sweden. Unfortunately, the subgroup with patients with diabetes and myocardial infarction (MI) in Paper I did not benefit from these favorable trends over the study period. For stroke, this is for the first time declining incidence has been reported in this population. Incidence of first-ever stroke decreased for non-diabetic men with a yearly change of -0.8 percent (p-value <0.001), and for diabetic women with a yearly change of -1.5 percent (p-value=0.012). Recurrent stroke incidence declined highly significant, p-value <0.001, for non-diabetic men and women and for diabetic women with a yearly change of -1.5, -2.7, and -5.4 percent, respectively. For diabetic men a non-significant decline of -1.0 percent (p-value=0.28) in stroke incidence was seen. Paper II showed that women with diabetes had decreased incidence for stroke but not men with diabetes. Also, reduced mortality from stroke was found in all patients except for diabetic women with first ever stroke.Patients with diabetes have altered fibrinolysis compared to individuals with normal glucose metabolism. Also, patients with prior MI manifest a hypofibrinolytic stage with low tissue-type plasminogen activator (tPA) activity and high levels of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Paper III showed a significant association between decreased tPA activity and increased fibrinogen levels in patients with a first MI when examined 3 months after the event. The results persisted even after adjustment for traditional risk factors and variables mirroring the insulin resistance syndrome and were significant in the whole study group of subjects with MI as well as for men alone.Paper IV, a 10 year follow-up study, showed that in patients with diabetes, tPA-activity significantly predicted the presence of sign(s) of lower extremity arterial disease (LEAD) at the baseline and at the 10-year follow-up. In addition, tPA-mass at the 10-year follow-up was associated with signs of LEAD. Baseline age, hypertension, and HbA1c were independently associated with sign(s) of LEAD at 10 years. This long-term study supports previous findings of a significant association between asymptomatic LEAD and tPA-activity. Thus, tPA-activity may be an early marker of LEAD, although the mechanism of this relationship remains unclear.Several studies report conflicting results regarding benefits and disadvantages of intensive insulin treatment. ORIGIN trial was an international multicenter trial studying effects of intensive insulin treatment on CVD. This thesis reports a Swedish sub-study of ORIGIN trial examining effects of insulin treatment on fibrinolysis. The allocation to insulin treatment did not significantly affect the studied fibrinolytic markers or von Willebrand factor (VWF) compared to the standard treatment. Log mean delta values between baseline and end of study increased significantly for tissue plasminogen activator activity (tPAact) and tPA/PAI-1 complex. For plasminogen activator inhibitor-1 (PAI-1), tPA antigen (tPAag) and VWF no significant differences were found. Within-group analysis during the whole study period revealed significant changes for tPA/PAI-1 complex, tPA antigen, and VWF in the insulin treatment group but no significant changes in the standard treatment group.The hypothesis that allocation to insulin treatment would improve the levels of markers of fibrinolysis or VWF compared to standard glucose lowering treatment could not be verified. Conclusion: This dissertation shows that patients with diabetes still have a heavy cardiovascular disease burden with increased risk for MI and stroke compared to individuals with normal glucose metabolism. This cardiovascular burden also includes increased morbidity, mortality, and poorer long-term prognosis. The fibrinolytic system has an impact on cardiovascular disease and this thesis has shown that patients with diabetes have unfavorable changes in their fibrinolysis and that alterations in fibrinolysis can predict future peripheral artery disease. However, intensive insulin therapy did not appear to affect this system to the extent of resulting in reduced cardiovascular morbidity.
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