| 1. |
- Norlén, Olov
(författare)
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Small Intestinal Neuroendocrine Tumor : A Rare Malignancy with Favorable Outcome
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small intestinal neuroendocrine tumor (SI-NET) is the most common small bowel tumor in Europe and USA, with an annual incidence of around 0.3-1.3/100000 persons. SI-NETs are the most common type of gastroenteropancreatic NETs (GEP-NETs), and they are known for their ability to produce hormones such as tachykinins and serotonin, as well as for their favorable long-term prognosis in comparison to gastrointestinal adenocarcinoma. The overall aim of the thesis was to investigate unknown or unclear aspects of SI-NET disease, in connection with prognosis, treatment and follow-up. Paper I confirmed several known negative prognostic factors and also showed, for the first time, that para-aortal lymph node metastases and peritoneal carcinomatosis were associated with worse survival by multivariable analyses. Locoregional surgery was associated with a low post-operative mortality, and a prolonged long-term survival by multivariable analysis. In Paper II we continued to investigate peritoneal carcinomatosis and found it be a risk factor not only for death, but also for emergency re-surgery. Furthermore, genetic analyses of samples from primary tumors in patients with and without peritoneal carcinomatosis showed a difference in the DNA between these two groups. In Paper III the outcome after liver surgery and/or radiofrequency ablation of liver metastases was investigated. To summarize, no difference in survival was seen in patients treated with surgery/radiofrequency ablation in comparison with matched controls. However, a superior radiological response of liver metasases and lower U-5-HIAA values were seen in patients subjected to liver surgery and/or radiofrequency ablation compared to matched controls. Paper IV compared ultrasonography, computed tomography and 11C-5HTP-PET in the follow-up after radiofrequency ablation of NET liver metastases. The study concluded that 11C-5HTP-PET depicted all residual tumors after RFA and that it, if used, should be combined with computed tomography for easier interpretation, as RFA areas are not clearly distinguishable with 11C-5HTP-PET alone. Paper V studied gallstone complications after somatostatin analog treatment in SI-NET patients, and concluded that there was a rather high risk to be subjected to a cholecystectomy due to biliary colic, cholecystitis, cholangitis or pancreatitis after primary surgery in somatostatin analog treated patients.
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| 2. |
- Schandl, Anna, et al.
(författare)
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Developing an early screening instrument for predicting psychological morbidity after critical illness
- 2013
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 17:5, s. Art. no. R210-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Guidelines recommend follow-up for patients after an intensive care unit (ICU) stay. Methods for identifying patients with psychological problems after intensive care would be of value, to optimize treatment and to improve adequate resource allocation in ICU follow-up of ICU survivors. The aim of the study was to develop a predictive screening instrument, for use at ICU discharge, to identify patients at risk for post-traumatic stress, anxiety or depression. Methods: Twenty-one potential risk factors for psychological problems - patient characteristics and ICU-related variables - were prospectively collected at ICU discharge. Two months after ICU discharge 252 ICU survivors received the questionnaires Post-Traumatic Stress Symptom scale -10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS) to estimate the degree of post-traumatic stress, anxiety and depression. Results: Of the 150 responders, 46 patients (31%) had adverse psychological outcome, defined as PTSS-10 >35 and/or HADS subscales >= 8. After analysis, six predictors were included in the screening instrument: major pre-existing disease, being a parent to children younger than 18 years of age, previous psychological problems, in-ICU agitation, being unemployed or on sick-leave at ICU admission and appearing depressed in the ICU. The total risk score was related to the probability for adverse psychological outcome in the individual patient. The predictive accuracy of the screening instrument, as assessed with area under the receiver operating characteristic curve, was 0.77. When categorizing patients in three risk probability groups - low (0 to 29%), moderate (30 to 59%) high risk (60 to 100%), the actual prevalence of adverse psychological outcome in respective groups was 12%, 50% and 63%. Conclusion: The screening instrument developed in this study may aid ICU clinicians in identifying patients at risk for adverse psychological outcome two months after critical illness. Prior to wider clinical use, external validation is needed.
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| 3. |
- Lankester, Arjan C, et al.
(författare)
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Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort.
- 2022
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 149:5
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome.We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome.HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed.Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P<.001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P< .001). Genetic subgroups did not differ in 2-year OS (P= .1) and EFS (P=.073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor-deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5×10e3/μL at+1 year were identified as independent predictors of favorable clinical and immunologic outcome.Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
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| 4. |
- Suzuki, C, et al.
(författare)
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The initial change in tumor size predicts response and survival in patients with metastatic colorectal cancer treated with combination chemotherapy
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 23:4, s. 948-954
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.PATIENTS AND METHODS: The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS).RESULTS: The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and <30%, albeit RECIST does not regard this as a partial response, was a positive prognostic factor for PFS and OS. Patients who had new lesions or unequivocal progression of nonmeasurable lesions had a worse prognosis than those with only an increase in size of >20%.CONCLUSIONS: The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.
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| 5. |
- Tiensuu Janson, Eva, et al.
(författare)
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Nordic guidelines 2021 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:7, s. 931-941
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Tidskriftsartikel (refereegranskat)abstract
- Background: The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic.Aim: These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians.
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| 6. |
- Hiswåls, Anne-Sofie
(författare)
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Employment Status and Inequalities in Health Outcomes : Population-based Studies from Gävleborg County
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: From a public health perspective, it is important not only to improve and maintain health, but also to promote equality in health. Epidemiological research has showed the importance of work and unemployment in the development of socio-economic health inequalities, and peoples life chances are suggested to be conditioned by participation or exclusion from the labour market. The most recent economic recession has brought further changes to the labour market that might have aggravated the already multifaceted image of inequalities in health. Gävleborg County was one of the hardest hit counties in Sweden, which experienced a myriad of changes in the labour market that went beyond those of the Swedish national average, in terms of increase in flexible forms of employment, factory closures, and lay-offs. The overall objective of this thesis was to investigate the relationship between employment status and health-related inequalities in Gävleborg County, Sweden. In addition, the Specific objectives for the thesis were to: assess the relationship between employment status and self-reported health in Gävleborg (Study I); to estimate the relationship between employment status and suicidal ideation during the economic recession in Gävleborg (Study II); to estimate the prevalence of anxiety and depression among economically active people living in the Municipality of Gävle (Study III) and to assess experiences and perceptions of well-being after involuntary job loss in Gävle (Study IV).Methods: Study I and II in this thesis used data from the 2010 Health in Equal Terms survey, a cross-sectional survey carried out in Gävleborg County in Sweden. A total of 4,245 individuals, aged 16–65 years were included in the analyses. Study III was performed in Wave 1 (baseline survey) of the Gävle Household, Labour Market Dynamics and Health Outcomes survey (GHOLDH), a panel survey with household as the follow-up unit. A total of 241 persons completed a self-administered postal questionnaire which collected information on the employment status and psychological health (anxiety and depression) among persons aged 18–65 years. The thesis used descriptive analyses and logistic regression models to describe and explore the relationship between employment status, self-reported health and suicidal ideation in Gävleborg County (Studies I and II). Descriptive analysis of means and a multiple regression analysis for adjusted means of HADS, were used in order to estimate the prevalence of anxiety and depression among economically active persons residing in the Gävle Municipality (Study III). Study IV used a qualitative approach to gain a deeper understanding of how involuntarily unemployed persons in Gävlexperceive their well-being. Sixteen unemployed men and women aged 28–62 were interviewed face-to-face. A purposeful sampling strategy was used in order to suit the research question and to increase the variation among informants. The interview texts in Study IV were analysed using thematic analysis.Results: In Study I, the prevalence of poor self-reported health (SRH) was twice as high in the group of people who were not employed (42%) compared to the employed group (21.6%). Individuals outside the labour market had odds of poor health of 2.64 (Cl 2.28–3.05) compared to their employed counterparts. Controlling for other covariates reduced the risk slightly to 2.10 (1.69–2.60), but remained statistically significant. Moreover, other variables such as long-standing illness, age, income and lack of social support were associated with self-reported poor health. In Study II, among those not employed, 11.2% had been in a situation where they had seriously considered taking their life (at some time during the past 12 months). The corresponding figure for those employed was 2.9%. Unadjusted results of the logistic regression analysis revealed that people who were not employed had about a four times higher risk of suicidal ideation, with an OR of 4.21 (CI: 3.14–5.64) compared to their employed counterparts. Controlling for other covariates, reduced the risk from 4.21(CI 3.14–5.64) in model I, to 1.73 (CI 1.16–2.57) in model IV, but remained statistically significant. In addition, other variables were associated with suicidal ideation. In Study III, the prevalence and risk of anxiety and depression were high among people who were out of work. In the multiple regression analysis, compared to employed people, those who were not employed had a risk of anxiety of 7.76 (5.97–9.75) and 4.67 (3.60–5.74) for depression. Study IV revealed six different themes from the interviews: Work was perceived as the basis for belonging; loss of work affected people’s social life and consumption patterns due to changes in their financial situation. Feelings of isolation, loss of self-esteem, and feelings of hopelessness were reported, affecting the respondents’ physical well-being. Longer duration of unemployment increased the respondents’ negative emotions. Activities, structure, and affiliation in other contexts were reported as part of their strategy for coping with poor mental health.Conclusion: This thesis found a statistically significant relationship between being outside the labour market and poor SRH, a high risk of suicidal ideation, anxiety, and depression during the recent economic recession. The relationship between employment status and SRH was partially explained by socioeconomic, demographic and lifestyle variables. In addition, the relationship between employment status and suicidal ideation was, for the most part, explained by demographic, socio-economic and self-reported psychological variables. Atxithe municipal level, the prevalence of anxiety and depression was higher among those who were out of the labour market as compared to those who were employed and the odds of anxiety and depression were higher among people out of the labour market, but this was less prominent for depression than for anxiety. Job loss created feelings of loss of dignity and belonging as a human being. The participants experienced feelings of worry, insecurity, and stress due to their changed financial situation, which in turn led to isolation and loss of self-esteem. Social support and having activities other than work gave structure and meaning to everyday life. The results of this thesis indicate a need for early detection and potential treatment of people out of the labour force and for being aware of the increased risk of poor health symptoms and disorders among unemployed individuals. The findings also indicate a need for primary prevention strategies, implying that policy-makers must pay attention to the health status of those who are out of work, especially during times of combined economic hardship and labour market fluctuations. However, longitudinal studies are warranted to shed further light on the mechanisms through which employment status and conditions impact physical and psychological health outcomes.
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| 7. |
- Bailey, Leslie, et al.
(författare)
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Small molecule inhibitors of type III secretion in Yersinia block the Chlamydia pneumoniae infection cycle
- 2007
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Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 581:4, s. 587-595
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular parasitism by Chlamydiales is a complex process involving transmission of metabolically inactive particles that differentiate, replicate, and re-differentiate within the host cell. A type three secretion system (T3SS) has been implicated in this process. We have here identified small molecules of a chemical class of acylated hydrazones of salicylaldehydes that specifically blocks the T3SS of Chlamydia. These compounds also affect the developmental cycle showing that the T3SS has a pivotal role in the pathogenesis of Chlamydia. Our results suggest a previously unexplored avenue for development of novel anti-chlamydial drugs.
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| 8. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 9. |
- Etminani, Farzaneh, 1984-, et al.
(författare)
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Randomised, siteless study to compare systematic atrial fibrillation screening using enrichment by a risk prediction model with standard care in a Swedish population aged ≥ 65 years : CONSIDERING-AF study design
- 2024
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Ingår i: BMJ Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study. METHODS AND ANALYSIS: CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups. ETHICS AND DISSEMINATION: This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: NCT05838781. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 10. |
- Jadidi, M, et al.
(författare)
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Evaluation of a new system for chest tomosynthesis : aspects of image quality of different protocols determined using an anthropomorphic phantom.
- 2015
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 88:1053, s. 20150057-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the image quality obtained with the different protocols in a new chest digital tomosynthesis (DTS) system.METHODS: A chest phantom was imaged with chest X-ray equipment with DTS. 10 protocols were used, and for each protocol, nine acquisitions were performed. Four observers visually rated the quality of the reconstructed section images according to pre-defined quality criteria in four different classes. The data were analysed with visual grading characteristics (VGC) analysis, using the vendor-recommended protocol [12-s acquisition time, source-to-image distance (SID) 180 cm] as reference, and the area under the VGC curve (AUCVGC) was determined for each protocol and class of criteria.RESULTS: Protocols with a smaller swing angle resulted in a lower image quality for the classes of criteria "disturbance" and "homogeneity in nodule" but a higher image quality for the class "structure". The class "demarcation" showed little dependency on the swing angle. All protocols but one (6.3 s, SID 130 cm) obtained an AUCVGC significantly <0.5 (indicating lower quality than reference) for at least one class of criteria.CONCLUSION: The study indicates that the DTS protocol with 6.3 s yields image quality similar to that obtained with the vendor-recommended protocol (12 s) but with the clinically important advantage for patients with respiratory impairment of a shorter acquisition time.ADVANCES IN KNOWLEDGE: The study demonstrates that the image quality may be strongly affected by the choice of protocol and that the vendor-recommended protocol may not be optimal.
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