Headache is the most frequently reported pain in children and is associated with missed schooldays, anxiety, depressive symptoms and various physical symptoms. A secular trend of increasing headache prevalence has been suggested. Few studies have focused on tension-type headache among children from the general population. The aims of this thesis were to describe the prevalence, incidence and prognosis of tension-type headache, migraine and overall headache in schoolchildren, to identify medical, psychological and social factors associated with these headache types, and to determine whether the prevalence of headache has increased over the last decades. In 1997, 1850 schoolchildren aged 7-15 years from the city of Uppsala participated in a questionnaire study and 1371 (74.1%) responded. Out of these, a randomly selected, stratified sample of 131 children and their parents were interviewed. Three years later, 122 children from the interview sample replied to an identical headache questionnaire. Compared with a similar study in 1955, a significantly lower proportion of schoolchildren reported no headache. The prevalence of tension-type headache increased with age and was significantly higher in girls than boys after the age of twelve. Similar age and gender differences were obtained for migraine. A higher proportion of girls reported frequent headache than boys. Children with headache, especially those with migraine, as well as their first-degree relatives suffered from other pains and physical symptoms more frequently than headache-free children and their first-degree relatives. Although the likelihood of experiencing the same headache diagnosis and symptoms at follow-up was high, about one fifth of children with migraine developed tension-type headache and vice versa. Female gender was a predictor of migraine and frequent headache a predictor of overall headache at follow-up. The estimated annual incidence for tension-type headache, migraine and overall headache was 81, 65 and 131 per 1000 children, respectively. In conclusion, the results indicate that headache has become increasingly common among schoolchildren over the last decades. Prevention and treatment of headache is particularly important for girls since they have high prevalence of headache, frequent headache episodes and a poor outcome. In children with headache, diagnoses and treatment should be reassessed regularly and other pains should be asked about and treated as well.

Esophageal carcinoma is a malignancy with a poor prognosis and is the sixth cause of cancer related death worldwide. In Sweden approximately 400 new cases are diagnosed every year. The aim of this present thesis was to investigate predictive factors for esophageal carcinoma patients.126 esophageal carcinoma patients admitted to the department of Oncology at the University Hospital in Uppsala between 1990-2000 were investigated with focus on known and potential prognostic factors. Performance status and stage of the disease were the only independent prognostic factors (p-values <0.001). Angiogenic factors VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p=0.04) whereas bFGF was not (p=0.08) in pre-treatment serum samples from 42 esophageal carcinoma patients. The use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, according to the results from the present study, seems limited. HER-2 overexpression was seen in 17% of 97 investigated esophageal tumor samples. In squamous cell carcinoma patients, HER-2 overexpression correlated with poorer survival (p=0.035), whereas in adenocarcinoma patients, HER-2 status did not. HER-2 overexpression seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma. Telomerase activity was detected in all esophageal cell lines, with a broad range of activity levels. No correlation was found between telomerase activity levels and sensitivity to investigated cytotoxic drugs. We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines. The virus HPV-16 was detected in 16 % of the patients; no other type HPV was detected. HPV-16 infection had no significant effect on survival (p=0.72). Our results did not show that HPV-16 increases survival or improve therapy response in patients with esophageal carcinoma.

A prognostic factor is a marker or a feature that can be used to estimate the risk of recurrence of disease, metastatic spread and clinical outcome. Despite intensive search for more sophisticated markers in renal cell carcinoma (RCC), few have added prognostic information to earlier described factors like stage of disease, nuclear grade, tumour type, and in metastatic disease; performance status, anaemia, hypercalcaemia and increased erythrocyte sedimentation. In the dominating tumour type, clear cell renal RCC (cRCC), hypoxia is common, leading to an up-regulation of hypoxia inducible factor (HIF). The majority of cRCC have a mutation in the von Hippel Lindau gene (VHL-gene), which regulates HIF and in turn leads to up-regulation of a number of target genes for potential growth factors. The aim of the study was to evaluate the possible prognostic information of a few factors associated to pVHL/HIF, anemia and/or hypercalcaemia in RCC; erythropoietin (EPO) and it´s receptor (EPO-R), carbonic anhydrase IX (CA IX), parathyroid hormone-related protein (PTHrP) and osteopontin (OPN). Patients diagnosed with RCC between 1982-2007 were included in the studies. The tumour tissue expressions of EPO, EPO-R and PTHrP were assessed using immunohistochemistry. Serum/plasma levels of EPO, CA IX, PTHrP and OPN were also analyzed using immunometric methods. Our study demonstrated that the expression of EPO and EPO-R were related, and the expressions differed significantly between RCC types. The serum EPO levels did not associate to the tumour expression of EPO or EPO-R, indicating that circulating EPO derives from other sources than tumour cells. Erythropietin receptor expression was more frequent in advanced stages of disease, but neither EPO, nor EPO-R, were independent prognostic factors for survival. Serum CA IX levels were higher in cRCC compared to papillary RCC (pRCC). In cRCC, the CA IX serum levels correlated positively to TNM stage, but serum CA IX did not add independent prognostic information. Parathyroid hormone-related protein is a cause of hypercalcaemia in malignancy, and we observed that circulating PTHrP related to hypercalcaemia in RCC. The tumour expression of PTHrP associated positively to serum PTHrP, but not to serum calcium. We found an association between PTHrP and OPN in plasma, and both plasma PTHrP and OPN were positively associated to TNM stage.  Neither serum/plasma PTHrP nor tumour expression of PTHrP were independent prognostic factors for survival. The serum OPN levels were higher in pRCC but no impact on survival was observed in this RCC type. In contrast, plasma/serum OPN was an independent prognostic factor for disease-specific survival in cRCC. Our results support a role for these factors in RCC. The expressions vary between tumour types, which can be explained by different gene aberrations. Some of the factors have a close relation to para-malignant symptoms like hypercalcaemia. Most of the factors correlate positively to TNM-stage, reflecting a relation to advanced disease. Although expression of EPO, EPO-R, PTHrP and CA IX did not add independent prognostic information, the results might contribute to greater understanding of important mechanisms and associations in RCC. Osteopontin is a strong independent prognostic factor in cRCC, and should be further evaluated as a tool in the clinic when treating RCC patients.

In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease. The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa. The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts. The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.

El objetivo de este estudio fue evaluar si la escala CURB-65, índice de mortalidad validado en neumonía comunitaria, podía aplicarse también en pacientes hospitalizados en Medicina Interna, donde no se han desarrollado escalas pronósticas. Para ello estudiamos prospectivamente una cohorte de 539 pacientes (51% varones; media de edad: 78 años; mortalidad: 12%) ingresados en el Hospital Sierrallana (Cantabria). Se recogieron diversos datos clínicos, epidemiológicos y analíticos. La puntuación en la escala CURB-65 fue significativamente más alta en los pacientes fallecidos (86% vs 30%; p<0,001), asociándose la puntuación alta con una mortalidad más elevada (RR 38,16 (5,16-281,5). La sensibilidad y especificidad de la puntuación alta fueron 85% y 69% respectivamente, y el valor predictivo negativo del 100%. También se calculó la curva ROC (área bajo la curva: 0,79). Nuestros resultados sugieren que la escala CURB-65 puede ser útil para predecir la mortalidad en pacientes hospitalizados en Medicina Interna. / The aim of this study was to evaluate if CURB-65 score, validated as mortality index in Community Acquired Pneumonia, could also be used in patients admitted to an Internal Medicine Service, where prognostic scores have not been developed. We analyzed prospectively a cohort of 539 patients (51% males; mean age: 78; mortality: 12%) admitted to Hospital Sierrallana (Cantabria). Clinical and epidemiological data and laboratory findings were examined. CURB-65 score was significantly higher in patients who died (86% vs 30%; p<0,001), and high CURB-65 score was associated with higher mortality (RR 38,16 (5,16-281,5)). Sensitivity and specificity for high CURB-65 score were 85% and 69%, respectively, and negative predictive value was 10%. Curve ROC was also calculated (area under the curve: 0,79). Our findings suggested that CURB-65 score can be an useful tool for predicting mortality in patients admitted to an Internal Medicine Service.

No description available.

This thesis presents an on-line particle-filtering-based framework for fault diagnosis and failure prognosis in nonlinear, non-Gaussian systems. The methodology assumes the definition of a set of fault indicators, which are appropriate for monitoring purposes, the availability of real-time process measurements, and the existence of empirical knowledge (or historical data) to characterize both nominal and abnormal operating conditions. The incorporation of particle-filtering (PF) techniques in the proposed scheme not only allows for the implementation of real time algorithms, but also provides a solid theoretical framework to handle the problem of fault detection and isolation (FDI), fault identification, and failure prognosis. Founded on the concept of sequential importance sampling (SIS) and Bayesian theory, PF approximates the conditional state probability distribution by a swarm of points called particles and a set of weights representing discrete probability masses. Particles can be easily generated and recursively updated in real time, given a nonlinear process dynamic model and a measurement model that relates the states of the system with the observed fault indicators. Two autonomous modules have been considered in this research. On one hand, the fault diagnosis module uses a hybrid state-space model of the plant and a particle-filtering algorithm to (1) calculate the probability of any given fault condition in real time, (2) estimate the probability density function (pdf) of the continuous-valued states in the monitored system, and (3) provide information about type I and type II detection errors, as well as other critical statistics. Among the advantages offered by this diagnosis approach is the fact that the pdf state estimate may be used as the initial condition in prognostic modules after a particular fault mode is isolated, hence allowing swift transitions between FDI and prognostic routines. The failure prognosis module, on the other hand, computes (in real time) the pdf of the remaining useful life (RUL) of the faulty subsystem using a particle-filtering-based algorithm. This algorithm consecutively updates the current state estimate for a nonlinear state-space model (with unknown time-varying parameters) and predicts the evolution in time of the fault indicator pdf. The outcome of the prognosis module provides information about the precision and accuracy of long-term predictions, RUL expectations, 95% confidence intervals, and other hypothesis tests for the failure condition under study. Finally, inner and outer correction loops (learning schemes) are used to periodically improve the parameters that characterize the performance of FDI and/or prognosis algorithms. Illustrative theoretical examples and data from a seeded fault test for a UH-60 planetary carrier plate are used to validate all proposed approaches. Contributions of this research include: (1) the establishment of a general methodology for real time FDI and failure prognosis in nonlinear processes with unknown model parameters, (2) the definition of appropriate procedures to generate dependable statistics about fault conditions, and (3) a description of specific ways to utilize information from real time measurements to improve the precision and accuracy of the predictions for the state probability density function (pdf).

DNA repair systems are indispensable for maintaining genomic integrity. Inherited polymorphisms of DNA repair systems related repair genes may contribute to individual variations in genetic susceptibility to oral cancer. We carried out a hospital-based case-control study to investigate the association of eight various polymorphisms in five DNA repair genes (XRCC1, XPA, XPC hMLH1 and XRCC3) with the risk for oral squamous cell carcinoma (OSCC). A total of 144 newly diagnosed OSCC and 215 frequency-matched controls were recruited between November 2003 and October 2004 at Kaohsiung Veterans General Hospital. Genotyping was performed using the PCR-RFLP techniques. In our results, we found that the XPA A23G polymorphism was strongly associated with OSCC risk (p for linear trend, 0.030) especially combined with XPC (p for linear trend, 0.026). Moreover a trend toward increased risk of OSCC was found when with the increasing putative high-risk genotypes of DNA repair genes (p for linear trend, 0.007). Therefore, we suggested that these polymorphisms in five repair genes were associated with the risk of OSCC. Furthermore, to investigate the prognosis of buccal carcinoma (BC), the most common site of oral cancer in Taiwan, we identified the protein expressions of XRCC1 and XPA and evaluated the relationship between expression level of proteins with clinicopathologic characteristics and survival outcome. A total of 138 primary BC specimens were recruited at KSVGH between 1994 and 2005 and the protein expression levels were identified by use of immunocytochemistry. The overall cumulative 5-years survival rate, 10-years survival rate and 12-years survival rate of BC patients were 66%, 55% and 44%, respectively. Survival curve of BC was significantly correlated with pathological stage, tumor size, lymph node metastasis, tumor differentiation, post-operative RT or CT. However, there were no significant differences between the survival curves of BC patients and the expression levels of XRCC1 and XPA, either in the univariate or the multivariate analysis. In conclusion, the combined effect of seven polymorphisms in five repair genes was associated with the risk of OSCC. However, the expression levels of XRCC1 and XPA were not associated with the survival for patients with BC.

Borderline Personality Disorder (BPD) is one of the more common personality disorder diagnoses observed in psychiatric inpatients and outpatients. Previous studies have found that individuals with BPD may be expected to experience difficulties throughout their lifetimes and they may repeatedly return for psychological treatment. Whereas previous studies have attempted to identify various factors related to relapse in other chronically recurring disorders such as depression, schizophrenia, and substance abuse, studies examining factors associated with relapse in BPD, and personality disorders in general, are absent from the scientific literature. This exploratory study examined whether specific risk and protective factors (dynamic and/or static) identified from the general relapse literature were associated with diagnostic relapse in BPD. Results revealed that variables related to an increased likelihood for BPD relapse included: substance abuse or Major Depressive Disorder, higher Neuroticism, and lower Conscientiousness. In addition, having a steady work or school status after remission was found to protect against a BPD relapse in the presence of various risk factors. Although this study has several limitations, these results provide some of the first insights to the processes of relapse and continued remission in BPD patients. Continued research efforts in this area can help to identify individuals who are at a greater risk for BPD relapse and potentially to design effective relapse-prevention strategies for the treatment of BPD.

The purpose of this study is to investigate whether a prolonged delay in diagnosis of bladder cancer will result in worse outcomes for those patients, compared to those patients with a shorter diagnostic time interval. Data was collected on 247 patients newly diagnosed with transitional cell carcinoma of the bladder from January 1996 to December 2006 (10 years). The medical records of these patients were reviewed for demographics, pathological stage, date of consultation to the genitourinary (GU) service, and date of diagnosis by transurethral resection of bladder tumor (TURBT). The specialty delay was calculated as the time between the date of consultation to the GU service to the establishment of a diagnosis by TURBT. Univariate analyses were performed to test the association of specialty delay with clinical features and all-cause mortality. The median specialty delay in this study was 100 days. There was a trend towards a longer specialty delay for muscle-invasive disease (T2-T4) in comparison to superficial disease (Ta and T1). There was a significant correlation between all-cause mortality and increasing clinical stage (p=0.01). There was a paradoxical finding that patients with a specialty delay greater than 100 days had a significant reduction in all-cause death in comparison to patients with a specialty delay of 100 days or less (relative risk=0.59; 95% CI 0.36-0.90; p=0.01). In conclusion, this study did not confirm the hypothesis that a prolonged specialty delay in patients diagnosed with bladder cancer would result in a worse prognosis. In fact, there was a paradoxical finding that patients with a specialty delay greater than the median delay of 100 days had a better prognosis.