Background: Co-morbidity of eating disorders and alcohol use among women is a topical theme. Eating disorders can be seen as a disease of modern women and alcohol use as very frequent and tolerated by society. Co-morbidity of these disorders is not given enough attention. Aim: The theoretical part defines basic terms of eating disorders, alcohol abuse and their co-morbidity. In the practical part my goal was to identify the risk and protective factors, personal characteristics that were common for women suffering with co-morbidity and to outline the subjective perception of respondents regarding this issue. Methods and sample: Data were obtained by the method of a semistructured interview with five respondents - clients of the aftercare group for alcohol addicts. Two methods were used for the purpose of data analysis: qualitative type of an approach and a pattern (gestalt) recognition method. Results: The thesis described risk factors on the individual, familial and social level. It also described personal characteristics of respondents that overlapped with the risk factors. They can therefore be taken as risk factors on the individual level. Protective factors are mainly positive influence of peers, hobbies and awareness of one's value. Respondents and their subjective view on this issue point out...

Vocal Cord Dysfunction (VCD) is characterized by paradoxical vocal cord movement during inspiration or expiration, and generally affects adolescents and predominantly women. Previous studies have shown a large inconsistency concerning terminology, definitions, etiology, assessment, differential diagnosis, co-morbidity and treatment. The purpose of this study was to map knowledge on and management of VCD in Sweden. The study was conducted as a written survey addressed to speech-language pathologists and physicians, and attained an answer percentage of 79 percent. The results showed that several professions were involved in the management of these patients, but no clear pattern of referral could be observed. The majority of the respondents considered intense physical exertion and psychological stress as triggering factors for VCD. Despite this, referral to a psychologist or psychiatrist seldom occurred. Asthma was the most frequent diagnosis regarding co-morbidity, and also the most frequent misdiagnosis. Respiratory exercises, relaxation and information about the diagnosis generally form the basis of VCD treatment. Physicians rated their knowledge on VCD greater compared to the speech-language pathologists. Several of the respondents stated that an increase in knowledge and awareness among nursing staff had contributed to an increase of patients with suspected or confirmed VCD. This study showed that there was no consensus regarding assessment, co-morbidity, misdiagnosis and treatment of VCD among speech-language pathologists and physicians in Sweden. / Vocal Cord Dysfunction (VCD) karakteriseras av paradoxala stämbandsrörelser vid in- eller utandning och drabbar vanligtvis ungdomar och huvudsakligen kvinnor. I tidigare studier framkom ingen konsensus kring terminologi, definition, etiologi, utredning, differentialdiagnostik, komorbiditet eller behandling. Syftet med föreliggande studie var att kartlägga kännedom om och handhavande av VCD i Sverige. Studien genomfördes i form av en enkätundersökning bland logopeder och läkare och svarsfrekvensen var 79 %. Ur resultatet framkom att flera professioner hade träffat dessa patienter men ingen tydlig remitteringsgång observerades. Majoriteten av respondenterna ansåg att intensiv fysisk ansträngning och psykologisk stress var utlösande faktorer till VCD. Däremot förekom sällan remittering till psykolog eller psykiater. Astma var den mest frekventa diagnosen gällande komorbiditet och feldiagnostisering. Andningsövningar, avspänning/avslappning samt information kring diagnosen inkluderades i behandlingen i hög grad. Läkarna skattade sin kunskapsnivå om VCD högre än logopederna. Flera av respondenterna angav att ökad kunskap och medvetenhet bland vårdpersonal hade bidragit till en ökning av diagnostisering av patienter med misstänkt eller konstaterad VCD. Föreliggande studie visade att det inte fanns någon enighet gällande utredning, komorbiditet, feldiagnostisering och behandling av VCD bland logopeder och läkare i Sverige.

Objectives. The first aim was to examine the effects of secondary prevention with a focus on determinants in the risk of recurrent coronary heart disease (CHD). The second aim was to analyse the effects of a cognitive behavioural therapy (CBT) intervention on the risk of recurrent cardiovascular disease (CVD) and to investigate the psychosocial situation of CHD patients. Material and methods. Papers I and II were based on the Swedish Acute Myocardial Infarction Statistics Register, 1969 to 2001: 775,901 events in 589,341 subjects. Papers III and IV were based on The Secondary Prevention in Uppsala Primary Care project (SUPRIM), a randomized controlled clinical trial in 362 CHD patients. Results. The risk of a recurrent acute myocardial infarction (AMI) event was highly dependent on time from the previous event, with the greatest risk immediately after an AMI event. In addition, sex, age, and AMI number influenced the general risk level. Furthermore, there has been a major decline in recurrence risk over 30 years, and there were considerable geographical differences in risk, best explained by residential area population density, with a high recurrent AMI risk in areas with the lowest and the highest population densities, and the lowest risk in areas with moderate population density. Disease status and sex were determinants of psychological well-being the first year after a CHD event. Sex seemed to be the stronger determinant. The CBT intervention focused on stress management during one year in patients with CHD.  There was significantly improved outcome in the intervention group on recurrent CVD and recurrent AMI during a 9 year follow up. A dose-response relationship was demonstrated between attendance rate at intervention group meetings and outcome, the higher the attendance rate the better the outcome. Conclusions. The risk of a recurrent AMI event was dependent on time from the previous event, with major improvement seen in recent decades. Regional differences were best explained by population density. Female CHD patients were at high risk concerning well-being after a coronary event, which deserves special attention. The CBT intervention for CHD patients improved outcomes concerning the risk of recurrent CVD and AMI events.

<p>Nonsteroidal anti-inflammatory drugs are among the most commonly used prescription and over-the-counter medications, but they often produce significant gastrointestinal ulceration and bleeding, particularly in elderly patients and patients with certain co-morbidities. Novel anti-inflammatory drugs are seldom tested in animal models that mimic the high-risk human users, leading to an underestimate of the true toxicity of these drugs. In the present study we examined the effects of two novel NSAIDs and two commonly used NSAIDs in models in which mucosal defence was expected to be impaired. Naproxen, celecoxib, ATB-346 (a hydrogen sulfide- and naproxen-releasing compound) and NCX 429 (a nitric oxide- and naproxen-releasing compound) were evaluated in healthy, arthritic, obese, hypertensive rats, and in rats of advanced age (19 months) and rats co-administered low-dose aspirin and/or omeprazole. In all models except hypertension, greater gastric and/or intestinal damage was observed when naproxen was administered in these models than in healthy rats. Celecoxib-induced damage was significantly increased when co-administered with low-dose aspirin and/or omeprazole. In contrast, ATB-346 and NCX 429, when tested at doses that were as effective as naproxen and celecoxib in reducing inflammation and inhibiting cyclooxygenase activity, did not produce significant gastric or intestinal damage in any of the models. These results demonstrate that animal models of human co-morbidities display the same increased susceptibility to NSAID-induced gastrointestinal damage as observed in humans. Moreover, two novel NSAIDs that release mediators of mucosal defence (hydrogen sulfide and nitric oxide) do not induce significant gastrointestinal damage in these models of impaired mucosal defence.</p> / Master of Science (MSc)

INTRODUÇÃO: Com o aumento da longevidade dos portadores de fibrose cística, o Diabetes Mellitus surgiu como sua primeira co-morbidade. Visando ao diagnóstico precoce, buscou-se maior compreensão do mecanismo fisiopatológico do Diabetes Mellitus Relacionado à Fibrose Cística (DRFC) através do estudo da resposta endócrina do pâncreas após dois tipos de estímulo. MÉTODOS: Neste estudo transversal, prospectivo e controlado conduzido entre junho de 2004 a agosto de 2005, foram comparadas as respostas de glicose, insulina, peptídeo-C, proinsulina e glucagon aos testes de sobrecarga com glicose (OGTT) e com dieta líquida (TTDM) realizados num intervalo inferior a 10 semanas, num grupo de 52 crianças e adolescentes com fibrose cística, entre 5 e 19 anos, acompanhadas na Unidade de Pneumologia Pediátrica do Instituto da Criança. RESULTADOS: O TTDM provocou uma hiperglicemia de menor duração (p < 0,05) e uma resposta mais precoce no tempo 30 minutos de insulina (p < 0,05), peptídeo-C (p < 0,05) e glucagon (p < 0,05), enquanto que o OGTT produziu uma hiperglicemia mais prolongada e respostas de insulina (p < 0,001), peptídeo-C (p < 0,001) e proinsulina (p < 0,001) mais tardias e sustentadas nos tempos 120 e 180 minutos. Ao grupo portador de DRFC sem hiperglicemia de jejum associaram-se níveis médios elevados de insulina (p < 0,05), peptídeo-C (p < 0,01) e proinsulina (p < 0,05) no tempo 120 minutos, revelando resistência insulínica. Houve sobreposição das respostas hormonais dos grupos normal, pré-diabético e diabético com hiperglicemia de jejum no tempo 120 minutos, sugerindo disfunção de célula beta nos dois últimos grupos. CONCLUSÕES: O estímulo da dieta líquida revelou uma resposta hormonal mais rápida provavelmente mediada pelos nutrientes diferentes da glicose. A resistência insulínica, além da disfunção da célula beta, está associada à fisiopatologia dos distúrbios glicêmicos da fibrose cística. / INTRODUCTION: Cystic fibrosis-related diabetes is a common complication leading to clinical deterioration of these patients. Aiming at an earlier diagnosis, we investigated the kinetics of the glucose-metabolism abnormalities by evaluating glucose, insulin, pro-insulin, C-peptide and glucagon responses after oral glucose (OGTT) and a mixed meal tolerance (MMTT) tests. METHODS: In a cross-sectional and controlled study, conducted from july/2004 till august/2005, 52 children and adolescents with cystic fibrosis, from 5 to 19 years old, underwent both tests in an interval of less than 10 weeks. RESULTS: Plasma glucose values were significantly lower during MMTT after 60 minutes and insulin, C-peptide and glucagon were secreted earlier, being significantly higher at 30 minutes. During OGTT, patients showed a delayed but higher peak insulin, C-peptide and pro-insulin secretion at time 120 minutes. Patients with Cystic Fibrosis-Related Diabetes (CFRD) without fasting hyperglycemia presented insulin, C-peptide and proinsulin values significantly higher than those patients with normal glucose tolerance or pre-diabetes, at time 120 minutes, indicating increased peripheral insulin resistance. An overlap of insulin, C-peptide and pro-insulin levels was observed in normal and pre-diabetic patients as well as in people with CFRD with fasting hyperglycemia, at 120 minutes, suggesting beta cell dysfunction in the latter groups. Conclusion: Mixed meal ingestion caused an earlier hormone secretion stimulated probably by nutrients different from glucose. Insulin resistance besides beta cell dysfunction are involved in the pathogenesis of cystic fibrosis related glucose disturbances.

INTRODUÇÃO: Com o aumento da longevidade dos portadores de fibrose cística, o Diabetes Mellitus surgiu como sua primeira co-morbidade. Visando ao diagnóstico precoce, buscou-se maior compreensão do mecanismo fisiopatológico do Diabetes Mellitus Relacionado à Fibrose Cística (DRFC) através do estudo da resposta endócrina do pâncreas após dois tipos de estímulo. MÉTODOS: Neste estudo transversal, prospectivo e controlado conduzido entre junho de 2004 a agosto de 2005, foram comparadas as respostas de glicose, insulina, peptídeo-C, proinsulina e glucagon aos testes de sobrecarga com glicose (OGTT) e com dieta líquida (TTDM) realizados num intervalo inferior a 10 semanas, num grupo de 52 crianças e adolescentes com fibrose cística, entre 5 e 19 anos, acompanhadas na Unidade de Pneumologia Pediátrica do Instituto da Criança. RESULTADOS: O TTDM provocou uma hiperglicemia de menor duração (p < 0,05) e uma resposta mais precoce no tempo 30 minutos de insulina (p < 0,05), peptídeo-C (p < 0,05) e glucagon (p < 0,05), enquanto que o OGTT produziu uma hiperglicemia mais prolongada e respostas de insulina (p < 0,001), peptídeo-C (p < 0,001) e proinsulina (p < 0,001) mais tardias e sustentadas nos tempos 120 e 180 minutos. Ao grupo portador de DRFC sem hiperglicemia de jejum associaram-se níveis médios elevados de insulina (p < 0,05), peptídeo-C (p < 0,01) e proinsulina (p < 0,05) no tempo 120 minutos, revelando resistência insulínica. Houve sobreposição das respostas hormonais dos grupos normal, pré-diabético e diabético com hiperglicemia de jejum no tempo 120 minutos, sugerindo disfunção de célula beta nos dois últimos grupos. CONCLUSÕES: O estímulo da dieta líquida revelou uma resposta hormonal mais rápida provavelmente mediada pelos nutrientes diferentes da glicose. A resistência insulínica, além da disfunção da célula beta, está associada à fisiopatologia dos distúrbios glicêmicos da fibrose cística. / INTRODUCTION: Cystic fibrosis-related diabetes is a common complication leading to clinical deterioration of these patients. Aiming at an earlier diagnosis, we investigated the kinetics of the glucose-metabolism abnormalities by evaluating glucose, insulin, pro-insulin, C-peptide and glucagon responses after oral glucose (OGTT) and a mixed meal tolerance (MMTT) tests. METHODS: In a cross-sectional and controlled study, conducted from july/2004 till august/2005, 52 children and adolescents with cystic fibrosis, from 5 to 19 years old, underwent both tests in an interval of less than 10 weeks. RESULTS: Plasma glucose values were significantly lower during MMTT after 60 minutes and insulin, C-peptide and glucagon were secreted earlier, being significantly higher at 30 minutes. During OGTT, patients showed a delayed but higher peak insulin, C-peptide and pro-insulin secretion at time 120 minutes. Patients with Cystic Fibrosis-Related Diabetes (CFRD) without fasting hyperglycemia presented insulin, C-peptide and proinsulin values significantly higher than those patients with normal glucose tolerance or pre-diabetes, at time 120 minutes, indicating increased peripheral insulin resistance. An overlap of insulin, C-peptide and pro-insulin levels was observed in normal and pre-diabetic patients as well as in people with CFRD with fasting hyperglycemia, at 120 minutes, suggesting beta cell dysfunction in the latter groups. Conclusion: Mixed meal ingestion caused an earlier hormone secretion stimulated probably by nutrients different from glucose. Insulin resistance besides beta cell dysfunction are involved in the pathogenesis of cystic fibrosis related glucose disturbances.

Abstract Morbid obesity is the most rapidly increasing health threat of developed countries, and the costs caused by it are already higher than those of smoking. In an increasing number of developing countries both starvation and morbid obesity are increasing simultaneously. Obesity in children and adolescents is also increasing rapidly. Conservative treatment almost invariably fails when treating morbid obesity. Results of pharmacotherapy have been disappointing after great expectations. Laparoscopic gastric banding has been used in the treatment of morbid obesity since 1993. The method was first used mostly in Europe. In the USA either an open or laparoscopic gastric bypass have been the most common methods of surgery. The aim of this study was to investigate the operation results of 280 patients operated in Vaasa Central Hospital during the 11 years after March 1996. Of these patients, 123 have been followed at least 5 years. The results have been analyzed with BAROS that measures the quality of life. Quality of life was measured prospectively 1 year after surgery with the 15D questionnaire that is validated in the Finnish population. The effect of gastric banding in esophageal motility and reflux was studied prospectively in 31 patients. Late results were analyzed in 123 patients 11 years after the first operation. Mean excess weight loss (EWL) was 56% in patients who had their band in place 7 years after surgery, and 46% in all patients. There was no mortality related to the operation, and there was only one serious complication. Disease-specific quality of life improved in 78.8% of the patients in 28 months of follow-up. Health-related quality of life was significantly improved 12 months after surgery, but improvement was not connected to the amount of weight loss. The band inhibited reflux 19 months after surgery. Complications, failures, and reoperations increase with longer follow-up. Weight loss is moderate 9 years after a gastric banding operation, and in carefully selected patients this operation is still a good option in the treatment of morbid obesity.

A prominent challenge in the healthcare system today is the limitation of resources in combi- nation with an increasing need for healthcare services. The pressure on healthcare is already extremely high and increasing due to a larger number of people seeking care as well as an aging population with an increased need for care. Therefore, it becomes more important to distribute resources effectively within healthcare to ensure high-quality care for everyone. Still, research shows that overcrowding of emergency departments and hospital wards is increasing affecting patient safety negatively with several negative implications including higher rates of medical errors and higher mortality. The problem is that healthcare is a complex system with many components that are interrelated and therefore hard to study with traditional approaches. Despite the huge quantity of studies on the overcrowding problem, there is yet to find a solution that could solve the problem. Thus, this thesis aims to design a data-driven pipeline to explore the clinical and logistical complexity of Emergency medicine patients admitted to hospital wards adopting a complex graph approach. Complex network theory provides a suitable tool to investigate complex networks by breaking complex systems down into smaller graphs with objects (nodes) and studying the relationship between these through various analysis tools. In this thesis, five complex networks were constructed representing co-morbidities in the car- diac, medicine, surgery, stroke, and orthopedic wards of the Academic Hospital of Uppsala, a hospital suffering from overcrowding. These networks were analyzed using degree distribution, centrality metrics, clustering coefficient, and community detection to reveal structural and clin- ical patterns. A comprehensive network of all hospital co-morbidities was also created and an- alyzed to compare it with the ward structures. Additionally, a network mapping patient flow from the emergency department based on chief complaints and ICD codes to wards was created and analyzed to identify admission patterns. The analysis of the co-morbidity networks revealed that there was an indication of structure between the wards. This was based on the visualization of nodes and edges of the networks, identified communities, and community comparisons between the wards. Further, it showed that there was a big overlap of common co-morbidities which could indicate the contrary. But it was also revealed that in terms of community structure, the wards were considerably different from each other indicating a good separation of diseases. The results of this research show that complex network theory could be used to increase the understanding of the complexity of healthcare wards in terms of the structure of diseases as well as clinical variability and allow for a discussion regarding if this is related to clinical or logistical factors. It also shows the potential of using complex network theory to increase the understanding of the path patients take from the emergency department to the wards based on the community detection analysis showing that there is a structure of where patient ends up based on the assigned ICD code and chief complaint in the emergency department. Previous studies have typically focused on specific diseases or patient flow within a single ward or the emergency department. This approach offers a tool to examine patient logistics across multiple wards alongside their clinical characteristics. The insights gained could help improve hospital structure by more efficiently distributing patients between wards, thereby enhancing resource use and hospital operations. Further research using complex network theory could deepen understanding of overcrowding issues and identify potential solutions. / En stor utmaning inom sjukvårdssystemet idag är begräsningen av resurser i kombination med ett ökat vårdbehov. Trycket på sjukvården är redan högt och ökar till följd av ett ökat antal personer som söker vård samt en åldrande befolkning med ett ökat vårdbehov. Därav blir det viktigare att fördela resurser inom sjukvården på ett effektivt sätt för att säkerställa en högkva- litativ vård till alla. Forskning visar dock att överbeläggningar på akutvårdsavdelningar och sjukvårdsavdelningar ökar vilket påverkar patientsäkerheten negativt med flera negativa kon- sekvenser däribland en högre andel medicinska misstag och en högre mortalitet. Problemet är att sjukvården är ett komplext system med många komponenter som samverkar och det är därav svårt att studera med traditionella tillvägagångssätt. Trots det höga antalet studier på överbeläggningar inom sjukvården behöver man fortfarande hitta en lösning på problemet. Därav är målet med denna avhandling att designa en datadriven pipeline för att undersöka den kliniska och logistiska komplexiteten hos patienter inlagda från akutvårdsavdelningen med hjälp av en komplex grafmetodik. Komplex nätverksteori är ett lämpligt verktyg för att studera komplexa nätverk genom att bryta ned det i mindre komponen- ter och undersöka sambanden mellan dem med hjälp av olika analysverktyg. I denna avhandling skapades 5 komplexa nätverk som representerade komorbiditeter utifrån tilldelad ICD-10-kod på hjärt-, medicin-, kirurgi-, stroke- och ortopediska avdelningen vid det akademiska sjukhuset i Uppsala, ett sjukhus som för närvarande lider av överbeläggningar. Nätverken analyserades med hjälp av gradfördelning, olika centralitetsmått, klusterkoefficient och samhällsdetektering för att identifiera skillnader eller likheter när det gäller struktur och klinisk variation. Ett heltäckande komplext nätverk skapades där alla komorbiditeter på hela sjukhuset inkluderades för att möjliggöra en jämförelse med strukturen på avdelningarna. Utö- ver detta, skapades och analyserades ett nätverk för att kartlägga patientflödet från akuten till sjukvårdsavdelningarna baserat på huvudorsak till patientens akutbesök och ICD kod. Analysen av samhällsstrukturen visade att det fanns en indikation av struktur mellan avdelning- arna. Detta baserat på visualisering av noder och kopplingar i nätverken, identifierade sam- hällen samt jämförelser av samhällen mellan avdelningarna. Vidare visade det dock att det fanns ett stort överlapp av vanliga komorbiditeter vilket kunde indikera motsatsen. Det visades dock att även när det gäller samhällsstruktur var avdelningarna väldigt olika vilket indikerade en god separering av sjukdomar. Resultaten av denna forskning visar att komplex nätverksteori kan användas för att öka förstå- elsen för komplexiteten på sjukvårdsavdelningarna gällande strukturen mellan sjukdomar såväl som klinisk variationen och öppnar upp för en diskussion om dessa är relaterade till kliniska eller logistiska faktorer. Det visar också potentialen att använda komplex nätverksteori för att öka förståelsen för den väg som patienterna tar från akutvårdsavdelningen till avdelningarna baserat på samhällsdetekteringsanalysen som visar att det finns en struktur av var patienten hamnar baserat på den tilldelade ICD-koden och huvudklagomål från akutvårdsavdelningen. Tidigare studier som har använt detta tillvägagångssätt har i huvudsak undersökt specifika sjuk- domar eller flöden på en specifik avdelning eller akutvårdsavdelning. Det här tillvägagångssät- tet ger ett verktyg för att utforska logistiken för patienters rutter till olika avdelningar samtidigt som deras kliniska egenskaper beaktas. Resultaten genom denna pipeline kan ge en grund för att öka förståelsen för hur man bättre kan strukturera sjukhuset genom att dela patienter mellanvavdelningar och genom detta effektivisera användningen av resurser och potentiellt förbättra rutiner på sjukhuset. Genom vidare studier, kan komplex nätverksteori användas för att öka förståelsen kring faktorer relaterade till problemet med överbeläggningar och hitta potentiella lösningar på problemet.