| 1. |
- Holmbom, Martin, 1984-
(författare)
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Clinical Impact of Bloodstream Infections – Characterization, Risk factors and Outcome
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bloodstream infection (blood poisoning) and antibiotic resistance are increasing worldwide, and already cause the loss of millions of human lives each year. According to the World Health Organisation (WHO), bloodstream infections (BSIs) represent 20% of global mortality on a par with cardiac infarct, stroke, and major trauma. BSI may occur when bacteria from a focus of infection gain access to the circulation (bacteraemia). BSIs are usually divided into two subclasses: community- and hospital-onset infections, since disease this involves different patient groups, types of bacteria, and reasons for infection. Compared to other countries, Sweden has been fortunate in having a relatively low death rate from BSI and low antibiotic resistance. However, as our lifestyle changes, the age of the population increases with more disease as a result, and as the healthcare system responds, death from infection and antibiotic resistance are on the increase. It is important that we recognise ”warning symptoms” if we are to manage BSIs correctly and initiate effective treatment. It is difficult to design individualised empirical treatment, so it is very important to be aware of risk factors for BSI and local resistance patterns, and to have an effective management programme. Bacterial resistance to antibiotics is an increasing problem, especially in bowel organisms that can cause infections that are very difficult to treat. In short, antibiotic resistance arises as a result of evolutionary processes where bacteria protect themselves by developing resistance genes. These genes can be exchanged between similar organisms or transmitted to others that in turn cause resistant infection. The use of antibiotics leads to an evolutionary/selection process leading to resistance in bacteria, both normal and pathogenic, enabling resistant organisms to survive, thrive, and go on to cause infection. Antibiotic resistance is a threat to global health. This thesis aims to increase our awareness of a large group of patients who suffer bloodstream infection. BSIs are increasing globally, and the death toll is high. Antibiotic resistance is an increasing threat to the health of the population, and we are inundated by alarming reports of resistance getting out of control. What is the situation in Sweden, and can we identify risk factors for BSI and mortality? In Study I, our aim was to study the incidence and mortality of BSI in Östergötland. To be able to do this, a large patient population stretching over several years was required. The study design was thus population-based in the form of an observational cohort study where all blood culture results from 2000 to 2013 were analysed, and evaluated from clinical data. A total of 109,938 results were analysed resulting in 11,480 BSIs. We saw that the incidence of BSI increased by 64% (mostly community-onset BSIs). We also saw that mortality increased by 45%. These results illustrate the importance of nationwide cooperation to combat the increasing problem of BSI and its mortality, and the establishment of a nationwide BSI register. The aim of Study II was to assess resistance development in Östergötland and its relationship to mortality. A total of 9,587 microorganisms were analysed between 2008 and 2016. We observed an increase in quinolone resistance (3.7-7.7%) and cephalosporin resistance (2.5-5.2%) amongst Enterobacteriaceae. We then looked at BSIs caused by multiresistant bacteria showing a total of 245 cases (2.6%); an increase of 300%. Despite this, we did not see an increased mortality in this group. There are several possible explanations for the increase in BSI mortality of which antibiotic resistance is a predominant factor globally. We were unable to show this in our study, even so mortality is increasing and is currently at a high level. In Study III we therefore analysed risk factors associated with death during a community-acquired BSI, focusing on preliminary prehospital and hospital management. In a retrospective case-control study on 195 deaths matched 1:1 regarding age, gender, and microorganism, with 195 survivors (controls). Results showed that many patients had contacted the primary healthcare system because of infection before they became severely ill, and that the strongest affectable risk factor for death was delay (>24h) between primary healthcare visit and admission to hospital. This shows the need for increased awareness in society and amongst the medical profession of those patients at risk and symptoms that should raise the alarm, leading to more rapid treatment. In Studies I and II we found an increase in both BSIs and mortality, we also saw an increase in antibiotic resistance and multiresistant bacteria, mainly ESBL-producing E. coli. On the other hand, we did not see any coupling between multiresistance and mortality in this Swedish population. E. coli is a gram-negative bacteria that causes most BSIs. Since E. coli is predominantly a urine tract pathogen, Study IV aimed to study BSIs caused by ESBL-producing E. coli originating from the urinary tract. We studied the prevalence of E. coli clones, resistance genes and risk factors, as well as any signs of increased mortality from ESBL-producing E. coli compared to sensitive E. coli. Our main finding was a surprisingly low mortality from ESBL-producing E. coli (3%). Most patients in the ESBL-producing E. coli group received inadequate antibiotic treatment for at least 48h, but we did not see any sign of increased mortality or risk for serious sepsis with circulatory failure in this group. This finding is interesting and opens up for new studies on virulence factors and immunological factors that govern the immune response to BSI. The implementation of cost-effective monitoring systems including clinical microbiological epidemiology and early identification of BSI, together with information campaigns aimed at the public as well as healthcare personnel regarding patients at risk and symptoms giving cause for alarm, should lead to a radical reduction in morbidity and mortality from BSI. This requires new diagnostic tools to individualise both antibiotic treatment and targeted management based on microorganism virulence factors. Modernisation of the medical journal system with algorithms aimed at early identification of risk patients and automated suggestions for empirical antibiotic treatment based on antibiotic resistance seen in previous cultures and local resistance patterns, would certainly improve management. Furthermore, new immunological tests showing the type of immunological reaction to a serious BSI will lead to individualised immunotherapy that, together with antibiotic treatment, will further improve patient care in this important group.
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| 2. |
- Sundell, Micaela, 1989-
(författare)
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Epidemiological and Clinical Aspects of Hormonal Contraception and Menopausal Hormone Therapy in Women
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The main indications for therapy with female sex hormones are contraception and menopausal hormone therapy (MHT). The aim of this thesis was to investigate the use of hormonal contraception and MHT in different populations of women in Sweden, 2000–2021. The use of contraception in women with obesity was studied. The use of MHT in Sweden over time was studied and different run-in periods were validated to define an incident MHT user. We also investigated the risk of pulmonary embolism (PE) in women using MHT, including considerations regarding administration form, treatment duration and type of progestin used. Women with premature or early menopause after bilateral oophorectomy were studied with regard to dispensed MHT.Material and Methods: The studies were based on different data sources including electronical medical records, national mandatory health registers, and a national quality register (GynOp). The use of MHT over time was studied using defined daily doses (DDD) per 1,000 women per day, one-year prevalence and incidence proportion. The definition of an incident drug user was validated by calculating the predictive value of different run-in periods.Results: The most prescribed contraceptive method in women with obesity was progestin-only pills (44%), but 21% were prescribed combined hormonal contraceptives contrary to Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within one year, compared with normal weight women. The use of MHT decreased significantly after the turn of the century. In the 50–54 years age interval, the dispensed amount decreased from 282 DDD/1,000 women per day in 2000, to 77 in 2006. It then stabilised around 50 DDD/1,000 women per day during 2010 to 2017. The one-year prevalence followed the same pattern, with a plateau 2010–2016. From 2017, an increase in MHT dispensations was observed. A run-in period of 18 months had a PV of 88% in the 50 to 54 years age group and was found to be suitable and reliable for defining incident users of MHT at the ages close to menopause. The risk of PE was significantly increased in users of oral MHT, but not transdermal. The risk was highest in first-ever users (OR 2.32; 95% CI, 1.34–4.00) and was considerably lower in women who may have used MHT previously (OR 1.38; 95% CI, 1.01–1.89). 69% of all women with a bilateral oophorectomy had at least one dispensation of MHT within one year after surgery. Within this treated group the estimated treatment time constituted 63% of the remaining time to natural menopause.Conclusions: Progestin-only pills was the most prescribed contraceptive method in women with obesity, but many women with obesity were prescribed combined hormonal contraceptives contrary to clinical guidelines. The use of MHT decreased significantly after the turn of the century, but has increased since 2017 in the age groups close to menopause. The classifications used for prevalent and incident drug use are of importance to the results. The risk of pulmonary embolism is increased in users of oral but not transdermal MHT. There seems to be a significant undertreatment with hormone therapy in women with premature, surgical menopause.
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| 3. |
- Bothelius, Kristoffer, 1973-
(författare)
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Cognitive Behavioural Therapy for Insomnia : How, for Whom and What about Acceptance?
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sleep is essential for survival but a significant minority of the adult population are dissatisfied with their sleep, and 6-10% meet the criteria for insomnia disorder, characterised by difficulties falling asleep at bedtime, waking up in the middle of the night or too early in the morning, and daytime symptoms. Cognitive behavioural therapy for insomnia (CBT-I), an evidence-based sleep-focused intervention, has been suggested as the treatment of choice for chronic insomnia. However, access to specialised sleep therapists is sparse, and a service delivery model based on the principles of ‘stepped care’ has been proposed. Even though CBT-I is shown to be effective, there is a need to continue the development of cognitive behavioural treatments for insomnia. As a complement to traditional interventions, the potential value of acceptance, that is, to make an active choice of openness towards psychological experiences, has been recognized. However, it has not yet been systematically investigated, and specific instruments for studying acceptance in insomnia are lacking.The present thesis is based on three studies: Study I showed that manual-guided CBT for insomnia delivered by ordinary primary care personnel has a significant effect on perceived insomnia severity, sleep onset latency and wake time after sleep onset. Study II demonstrated that non-responders in Study I reported shorter sleep time at baseline than did responders, a notion that may help select patients for this type of low-end intervention in a stepped care treatment approach. Study III aimed to develop a new assessment instrument for studying acceptance of insomnia, the Sleep Problem Acceptance Questionnaire (SPAQ), resulting in an eight-item questionnaire with two factors; the first being Activity Engagement, persisting with normal activities even when sleep is unsatisfactory, and the second involving Willingness, avoiding fighting and trying to control sleep problems.In conclusion, the present thesis demonstrates that it is feasible to treat patients with insomnia using CBT-I administrated by ordinary primary care personnel in general practice, and that those with relatively longer initial sleep duration benefit most from treatment, enabling allocation to relevant treatment intensity. In addition, acceptance of sleep difficulties may be quantified using the SPAQ.
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| 4. |
- Frick, Andreas
(författare)
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Imaging Anxiety : Neurochemistry in Anxiety Disorders Assessed by Positron Emission Tomography
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anxiety disorders, including social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD) are common and disabling conditions. Largely based on animal and pharmacological studies, both the serotonergic and substance P/neurokinin-1 (SP/NK1) systems have been implicated in their underlying pathology. However, only few neuroimaging studies have directly assessed these neurotransmitter systems in human sufferers of anxiety disorders, and none have addressed possible between-systems relationships.The overall aim of this thesis was to study possible neurochemical alterations associated with anxiety disorders. To this end, three studies using positron emission tomography (PET) for in-vivo imaging of the brain serotonergic and SP/NK1 systems in patients with SAD and PTSD were conducted. The radiotracers [11C]5-HTP, [11C]DASB, and [11C]GR205171 were used to index serotonin synthesis rate, serotonin transporter (SERT) availability, and NK1 receptor availability respectively.In Study I, patients with SAD relative to controls exhibited enhanced serotonin synthesis rate and serotonin transporter availability. Serotonin synthesis rate in the amygdala was positively related to social anxiety symptom scores. Study II demonstrated increased NK1 receptor availability in the amygdala in patients with SAD relative to controls. In Study III, patients with PTSD showed elevated NK1 receptor availability in the amygdala as compared to controls. SERT availability in the amygdala was negatively related to PTSD symptom severity, a relationship that was moderated by NK1 receptor levels. The regional overlap between SERT and NK1 receptor expression was altered in patients with PTSD, with reduced overlap linked to more severe symptoms.Collectively, the findings are consistent with the view that serotonin in the amygdala induces rather than reduces anxiety and links exaggerated anxiety to an overactive presynaptic serotonin system. In addition, the involvement of the SP/NK1 system in stress and anxiety, as suggested by animal studies, was demonstrated in two common human anxiety disorders. Finally, PTSD symptomatology is better accounted for by interactions between the serotonergic and SP/NK1 systems in the amygdala than by each system separately. In conclusion, this thesis supports that both the serotonergic and SP/NK1 systems in and of themselves, but also interactively, may be important contributors to anxiety symptomatology.
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| 5. |
- Henriksson, Maria P.
(författare)
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Human Rationality : Observing or Inferring Reality
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the boundary of human rationality and how psychological processes interact with underlying regularities in the environment and affect beliefs and achievement. Two common modes in everyday experiential learning, supervised and unsupervised learning were hypothesized to tap different ecological and epistemological approaches to human adaptation; the Brunswikian and the Gibsonian approach. In addition, they were expected to be differentially effective for achievement depending on underlying regularities in the task environment. The first approach assumes that people use top-down processes and learn from hypothesis testing and external feedback, while the latter assumes that people are receptive to environmental stimuli and learn from bottom-up processes, without mediating inferences and support from external feedback, only exploratory observations and actions.Study I investigates selective supervised learning and showed that biased beliefs arise when people store inferences about category members when information is partially absent. This constructivist coding of pseudo-exemplars in memory yields a conservative bias in the relative frequency of targeted category members when the information is constrained by the decision maker’s own selective sampling behavior, suggesting that niche picking and risk aversion contribute to conservatism or inertia in human belief systems. However, a liberal bias in the relative frequency of targeted category members is more likely when information is constrained by the external environment. This result suggests that highly exaggerated beliefs and risky behaviors may be more likely in environments where information is systematically manipulated, for example when positive examples are highlighted to convey a favorable image while negative examples are systematically withheld from the public eye.Study II provides support that the learning modes engage different processes. Supervised learning is more accurate in less complex linear task environments, while unsupervised learning is more accurate in complex nonlinear task environments. Study III provides further support for abstraction based on hypothesis testing in supervised learning, and abstraction based on receptive bottom-up processes in unsupervised learning that aimed to form ideal prototypes as highly valid reference points stored in memory. The studies support previous proposals that integrating the Brunswikian and the Gibsonian approach can broaden the scope of psychological research and scientific inquiry.
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| 6. |
- Michelgård Palmquist, Åsa, 1973-
(författare)
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Positron Emission Tomography (PET) Studies in Anxiety Disorders
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anxiety disorders are very common and the primary feature is abnormal or inappropriate anxiety. Fear and anxiety is often mediated by the amygdala, a brain structure rich in substance P (SP) and neurokinin 1 (NK1) receptors. To learn more about how the human amygdala is modulated by fear and anxiety in event-triggered anxiety disorders and to investigate if the SP/NK1 receptor system is affected, regional cerebral blood flow (rCBF) ([15O]-water; Study I and II) and the SP/NK1 receptor system ([11C]GR205171; Study III and IV) were studied with positron emission tomography (PET). In Study I we investigated the neural correlates of affective startle modulation in persons with specific phobia by measuring rCBF during exposure to fearful and non-fearful pictures, paired and unpaired with acoustic startle stimuli. Fear-potentiated startle was associated with activation of the affective part of the anterior cingulate cortex and the left amygdaloid–hippocampal area. In Study II short-term drug treatment effects on rCBF in patients diagnosed with social phobia was evaluated, comparing the NK1 receptor antagonist GR205171 to the selective serotonin reuptake inhibitor citalopram and placebo. Social anxiety and neural activity in the medial temporal lobe including the amygdala was significantly reduced by both drugs but not placebo. In Study III we investigated if activity in the SP/NK1 receptor system in the amygdala would be affected by fear provocation in individuals with specific snake or spider phobia. Fear provocation was associated with a decreased uptake of the NK1 antagonist [11C]GR205171 in the amygdala, possibly explained by an increase in endogenous SP release occupying the NK1 receptors. Study IV was conducted to explore the resting state NK1 receptor availability in PTSD patients as compared to healthy controls. Increased resting state binding of the tracer [11C]GR205171 in the amygdala of patients with PTSD suggested an increased amount of available receptors. In summary, fear and fear-potentiated startle modulates the human amygdala, possibly through the SP/NK1 receptor system.
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| 7. |
- Parenmark, Fredric, 1974-
(författare)
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Premature Discharge from Intensive Care with Special Reference to Night-Time Discharge and Capacity Transfers
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives Intensive care is an expensive and limited resource, and when a demand supply mismatch between available beds and influx of patients occurs, one temporary measure is to discharge a patient to make room for the new admission. Sometimes the patient is discharged sooner from its original ICU than ideal; i.e., a so-called ‘premature discharge’. This could be either to a different ward within the same hospital if the patient is deemed well enough to cope with a lower level of care, or to another intensive care unit if critical care is still to be provided. Data from the Swedish intensive care register (SIR) showed that there was a high incidence and increased mortality of patients discharged at night. There were also differences in mortalities between patients that were transferred from one ICU to another. I have analysed the mortality associated with different types of ICU-to-ICU transfers and control groups and examined a national quality improvement project regarding discharges at night to see if mortality, incidence, or discharge culture could change. Methods All three studies are conducted with data from the Swedish intensive care register and vital status was ascertained by linking SIR to the Swedish population register. Study I consisted of two parts: mortality, and incidence of night-time discharge. The quality improvement project in Study I was analysed in a before and after approach with local improvement projects at different ICUs. In Studies II and III, transfers were grouped by the attending intensivist according to SIR guidelines into one of three defined categories: capacity transfer, clinical transfer, or repatriation. The groups were compared to each other in Study II, and capacity transfers were matched to a control group that remained in the ICU in Study III. Multilevel logistic regression was used, and all studies contained some statistics using individual ICUs as a random factor. Life sustaining treatment limitations were included in Studies II and III. Results In Study I, there was a decrease in night-time discharges during the study period. The incidence fell from 7.0% in 2006 to 4.9% in 2015. Alongside this, the mortality associated with night-time discharge was reduced, the odds ratio fell from 1.20 to 1.06 with a loss of significance. All this coincided in time with the national improvement project. Study II showed that 14.8% of all discharges from a Swedish ICU ended with transfer to another ICU, and that an increased mortality rate was associated with ICU-to-ICU transfers during periods of demand–supply mismatch. Capacity transfers were 15.8% of all transfers accounting for roughly 2.0% of ICU survivors. One in four capacity transferred patient died within 30 days of discharge, compared to one in seven for transfers due to clinical reasons. The third study showed that capacity transfer was associated with an average risk increase in 30-day mortality of 4.7%, and a 180-day mortality of 4.9% compared to non-transferred patients when analysed using a potential outcomes framework. Conclusion The studies concludes that patients experiencing a capacity transfer are exposed to increased mortality risk, both when compared to other types of inter hospital ICU-to-ICU transfers as well as when compared to patients that were not transferred. The increased risk appeared to be unrelated to patient characteristics and illness severity as well as many additional factors measured in the referring ICU. The studies also suggest that a suboptimal outcome after premature discharge at night can be changed and that a national project to adjust outcome and incidence can be undertaken with positive results.
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| 8. |
- Strömbom, Ylva, 1959-
(författare)
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Frequent attenders in primary care : Patient characteristics, help seeking patterns and cognitive behavioral therapy
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Frequent attenders consist of a small proportion of the total population seek-ing health care non-proportionally often for various symptoms. This hetero-genic group of patients requires special attention as symptoms often cannot be explained medically and influence both physical and psychological well-being.The overall aim was to describe characteristics and health issues that insti-gate help seeking behavior among frequent attenders and to piece together a treatment program addressing heterogeneous health problems with the pur-pose to reduce psychological distress, enhance quality of life and reduce visiting rates at general practitioners. Study I aimed to characterize frequent attenders in primary care with respect to symptomatology and utilization of health care resources. Data was collected from medical journals and compar-isons were made between frequent attenders and a comparison group. Among frequent attenders proportionally more women than men visited the health care system and both sexes had a large diversity and amount of health complaints and utilized health care staff resources more frequently. In study II health related quality of life was examined in relation to frequent attend-ance. Questionnaires were sent out to frequent attenders and a comparison. Results show a substantially reduced life quality among frequent attenders affecting almost all facets of life and individual differences in complaints translated into corresponding areas of reduced life quality. Cognitive behav-ior therapy given in a group format was performed and evaluated in study III. Improvements of illness symptoms and negative affect were found and remained over a year, but visits to health care did not diminish.In summation, frequent attenders used more health care resources and dis-played more health complaints as compared to non-frequent attenders. The nature of complaints was relatively independent suggesting symptom speci-ficity. They also experienced lower health related quality of life and symp-tom profiles matched domains with reduced life quality. Group CBT may be an efficient way to deal with some aspects related to health issues connected to frequent attenders. Generally, a biopsychosocial model seemed to account better for data than a purely biological model.
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| 9. |
- Thunberg, Monika, 1963-
(författare)
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Rapid Facial Reactions to Emotionally Relevant Stimuli
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis investigated the relationship between rapid facial muscle reactions and emotionally relevant stimuli. In Study I, it was demonstrated that angry faces elicit increased Corrugator supercilii activity, whereas happy faces elicit increased Zygomaticus major activity, as early as within the first second after stimulus onset. In Study II, during the first second of exposure, pictures of snakes elicited more corrugator activity than pictures of flowers. However, this effect was apparent only for female participants. Study III showed that participants high as opposed to low in fear of snakes respond with increased corrugator activity, as well as increased autonomic activity, when exposed to pictures of snakes. In Study IV, participants high as opposed to low in speech anxiety responded with a larger difference in corrugator responding between angry and happy faces, and also with a larger difference in zygomatic responding between happy and angry faces, indicating that people high in speech anxiety have an exaggerated facial responsiveness to social stimuli. In summary, the present results show that the facial EMG technique is sensitive to detecting rapid emotional reactions to different emotionally relevant stimuli (human faces and snakes). Additionally, they demonstrate the existence of differences in rapid facial reactions among groups for which the emotional relevance of the stimuli can be considered to differ.
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| 10. |
- Bäckström, Denise, 1976-
(författare)
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Injury mortality in Sweden; changes over time and the effect of age and injury mechanism
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Injuries are one of the most common causes of death in the world. Varying types of injuries dominate in different parts of the world, which also have separate influences mortality. In Scandinavia blunt injuries dominates and the majority of those who die do so pre hospital. Over time different injury pattern may vary and by analyzing this we can assess when, where and how preventive work can be reinforced. The aim of this thesis was to study injury epidemiology in Sweden and assess the contribution of different injury patters on mortality. Method: We used the Swedish cause of death and the national patient registries which have a complete national coverage. ICISS was calculated (based on ICD-10) in the in hospital population. We have chosen to do this investigation with a broad perspective using the term injury, which includes trauma but also other diagnoses like suffocation and drowning. Results: During the study period (1999-2012) the number of deaths because of injury was 1213, 25 388, and 18 332 among children, working age and elderly, respectively. Mortality declined in the children and in the working age but inclined in the elderly. Mortality increased with each age group except between the ages of 15–25 and 26–35 years. One thousand two hundred sixty four (97%) of those who died because of penetrating trauma (sharp objects and firearms) were killed by intentional trauma (assault and intentional self-harm). One thousand and seventeen (83%) of the children died prehospital. In the working age 22 211 (80%) of 25 388 died pre hospital. Nine thousand six hundred and eighteen (53%) of 18 332 of the elderly died prehospital. During 2001- 2011 the risk adjusted in hospital mortality decreased in traffic and assault but not in fall related injuries. Discussion: Largely, the anticipated injury mortality picture was found, with blunt injuries (traffic accidents) dominating in the working age and falls in elderly. Further a significant portion of the deaths occurred pre hospital. The intentional injuries are dominated by intentional selfharm. The decrease in child injury mortality is notable as Sweden already has one of the lowest incidences in child injury mortality in the world. The decrease in injury mortality in the working age also implies that preventive work has had an effect. The incline in injury mortality in elderly on the other hand needs to be further studied. Areas of particular importance for future preventive work is the incline in injury mortality in elderly and intentional injuries among children.
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