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1.
  • Persson, Lena, 1951-, et al. (författare)
  • Acute leukaemia and malignant lymphoma patients' experiences of disease, treatment and nursing care during the active treatment phase : an explorative study
  • 1995
  • Ingår i: European Journal of Cancer Care. - : John Wiley & Sons Inc.. - 0961-5423 .- 1365-2354. ; 4:3, s. 133-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Five acute leukaemia or high malignant lymphoma patients at a hospital in southern Sweden were interviewed about their daily living problems, their coping strategies and their opinions about the nursing care they received during the active phase of their treatment. In addition the EORTC QLQ-C30, the Global Life Quality and the Sense of Coherence scales were administered. The data were analysed from a hermeneutic phenomenological perspective and interpreted to indicate that the patients sensed a threat to their lives, loss of control and having to live in uncertainty stemming from the disease and the treatment. They had problems with such things as fatigue, diarrhoea, nausea and vomiting, loss of appetite, sore mouth, and high temperature. However they seemed to minimise the importance of these problems and instead focused on gaining control of the situation, developing their knowledge of the disease and relying on the  support of their family. Contradictions appeared in their statements about the quality of care; the information given was said to be good but difficult to understand, though the quality of the nursing care was judged to be high it had to be asked for i.e. help was received on request. In conclusion the entire situation of the patients perspective of both from the family and the nurses, needs to be studied in further research in order to fully understand the patients´ coping strategies and how nursing care can support them.
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2.
  • Bjurberg, Maria, et al. (författare)
  • Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer
  • 2009
  • Ingår i: International Journal of Gynecological Cancer. - Philadelphia : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 19:9, s. 1600-1605
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.
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3.
  • Björkwall, Susanna, et al. (författare)
  • A generalized linear model with smoothing effects for claims reserving
  • 2011
  • Ingår i: Insurance, Mathematics & Economics. - : Elsevier BV. - 0167-6687 .- 1873-5959. ; 49:1, s. 27-37
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we continue the development of the ideas introduced in England and Verrall (2001) by suggesting the use of a reparameterized version of the generalized linear model (GLM) which is frequently used in stochastic claims reserving. This model enables us to smooth the origin, development and calendar year parameters in a similar way as is often done in practice, but still keep the GLM structure. Specifically, we use this model structure in order to obtain reserve estimates and to systemize the model selection procedure that arises in the smoothing process. Moreover, we provide a bootstrap procedure to achieve a full predictive distribution.
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4.
  • Björkwall, Susanna, et al. (författare)
  • Bootstrapping the separation method in claims reserving.
  • 2010
  • Ingår i: Astin Bulletin. - 0515-0361 .- 1783-1350. ; 40:2, s. 845-869
  • Tidskriftsartikel (refereegranskat)abstract
    • The separation method was introduced by Verbeek (1972) in order to forecast numbers of excess claims and it was developed further by Taylor (1977) to be applicable to the average claim cost.The separation method differs from the chain-ladder in that when the chain-ladder only assumes claim proportionality between the development years, the separation method also separates the claim delay distribution from influences affecting the calendar years, e.g. inflation. Since the inflation contributes to the uncertainty in the estimate of the claims reserve it is important to consider its impact in the context of risk management, too. In this paper we present a method for assessing the prediction error distribution of the separation method. To this end we introduce a parametric framework within the separation model which enables joint resampling of claim counts and claim amounts. As a result, the variability of Taylor's predicted reserves can be assessed by extending the parametric bootstrap techniques of Björkwall et al. (2009). The performance of the bootstrapped separation method and chain-ladder is compared for a real data set.
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5.
  • Björkwall, Susanna, 1976-, et al. (författare)
  • Non-parametric and parametric bootstrap techniques for age-to-age development factor methods in stochastic claims reserving.
  • 2009
  • Ingår i: Scandinavian Actuarial Journal. - : Informa UK Limited. - 0346-1238 .- 1651-2030. ; :4, s. 306-331
  • Tidskriftsartikel (refereegranskat)abstract
    • In the literature, one of the main objects of stochastic claims reserving is to find models underlying the chain-ladder method in order to analyze the variability of the outstanding claims, either analytically or by bootstrapping. In bootstrapping these models are used to find a full predictive distribution of the claims reserve, even though there is a long tradition of actuaries calculating the reserve estimate according to more complex algorithms than the chain-ladder, without explicit reference to an underlying model. In this paper we investigate existing bootstrap techniques and suggest two alternative bootstrap procedures, one non-parametric and one parametric, by which the predictive distribution of the claims reserve can be found for other age-to-age development factor methods than the chain-ladder, using some rather mild model assumptions. For illustration, the procedures are applied to three different development triangles.
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6.
  • Björkwall, Susanna, 1976- (författare)
  • Stochastic claims reserving in non-life insurance : Bootstrap and smoothing models
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In practice there is a long tradition of actuaries calculating reserve estimates according to deterministic methods without explicit reference to a stochastic model. For instance, the chain-ladder was originally a deterministic reserving method. Moreover, the actuaries often make ad hoc adjustments of the methods, for example, smoothing of the chain-ladder development factors, in order to fit the data set under analysis. However, stochastic models are needed in order to assess the variability of the claims reserve. The standard statistical approach would be to first specify a model, then find an estimate of the outstanding claims under that model, typically by maximum likelihood, and finally the model could be used to find the precision of the estimate. As a compromise between this approach and the actuary's way of working without reference to a model the object of the research area has often been to first construct a model and a method that produces the actuary's estimate and then use this model in order to assess the uncertainty of the estimate. A drawback of this approach is that the suggested models have been constructed to give a measure of the precision of the reserve estimate without the possibility of changing the estimate itself. The starting point of this thesis is the inconsistency between the deterministic approaches used in practice and the stochastic ones suggested in the literature. On one hand, the purpose of Paper I is to develop a bootstrap technique which easily enables the actuary to use other development factor methods than the pure chain-ladder relying on as few model assumptions as possible. This bootstrap technique is then extended and applied to the separation method in Paper II. On the other hand, the purpose of Paper III is to create a stochastic framework which imitates the ad hoc deterministic smoothing of chain-ladder development factors which is frequently used in practice.
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7.
  • Bohlooly-Yeganeh, Mohammad, 1966, et al. (författare)
  • Enhanced spontaneous locomotor activity in bovine GH transgenic mice involves peripheral mechanisms
  • 2001
  • Ingår i: Endocrinology. ; 142:10, s. 4560-4567
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical and experimental studies indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. Recently we showed that transgenic mice with general overexpression of bovine GH display increased spontaneous locomotor activity. In the present study, we investigated whether this behavioral change is owing to a direct action of GH in the central nervous system or to peripheral GH actions. A transgenic construct, containing the glial fibrillary acidic protein promoter directing specific expression of bovine GH to the central nervous system, was designed. The central nervous system-specific expression of bovine GH in the glial fibrillary acidic protein-bovine GH transgenic mice was confirmed, but no effect on spontaneous locomotor activity was observed. Serum bovine GH levels were increased in glial fibrillary acidic protein-bovine GH transgenic mice but clearly lower than in transgenic mice with general overexpression of bovine GH. In contrast to the transgenic mice with general overexpression of bovine GH, glial fibrillary acidic protein-bovine GH mice did not display any difference in serum IGF-I levels. The levels of free T(3) and the conversion of the free T(4) to free T(3) were only increased in transgenic mice with general overexpression of bovine GH, but serum corticosterone levels were similarly increased in both transgenic models. These results suggest that free T(3) and/or IGF-I, affecting dopamine and serotonin systems in the central nervous system, may mediate the enhanced locomotor activity observed in transgenic mice with general overexpression of bovine GH.
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8.
  • Bondesson, Susanne, et al. (författare)
  • Effects on blood pressure in patients with refractory angina pectoris after enhanced external counterpulsation
  • 2010
  • Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 19:5, s. 287-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to reduce the frequency and severity of angina pectoris. Little is known how EECP affects the blood pressure. Methods. 153 patients with refractory angina were treated with either EECP or retained on their pharmacological treatment (reference group). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and heart rate were measured pre- and post-treatment and at 12 months follow-up. Results. EECP treatment altered the blood pressure in patients with refractory angina pectoris. A decrease in the blood pressure was more common in the EECP group compared with the reference group. In the reference group, an increase in the blood pressure was more common. A correlation between a decrease in blood pressure after EECP treatment and a higher baseline MAP, SBP and DBP was seen. No such correlation was seen in the reference group. The blood pressure response did not persist at 12 months follow-up. Conclusion. EECP treatment affects the blood pressure in patients with refractory angina pectoris. The decreased blood pressure may be a result of an improved exercise capacity, an improved endothelial function and vasoreactivity in general.
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9.
  • Borg, Julia, et al. (författare)
  • Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus.
  • 2007
  • Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 24:11, s. 1235-1239
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. Methods Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. Results Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. Conclusion Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other.
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10.
  • Claesson, Åsa, et al. (författare)
  • lntegrated Optical Fiber Sensors in Additive Manufactured Metal Components for Smart Manufacturing Applications
  • 2019
  • Ingår i: Smart Systems Integration; 13th International Conference and Exhibition on Integration Issues of Miniaturized Systems.
  • Konferensbidrag (refereegranskat)abstract
    • This work combines fiber optic sensors with additive manufacturing to enable integration of temperature and strain sensors in metal components. In this paper, we present a fiber optic sensor network integrated in press hardening tools to monitor the contact between the tool and the metal sheet during forming operation. The tools are manufactured through metal powder bed fusion using laser melting processes (PBF-SLM), after which the tools are prepared for sensor integration. A demonstrator press hardening tool with integrated fiber optic sensors was heated using an electric heat foil and the sensor measurements was compared to a thermal simulation model. The sensor technology is based on Fiber Bragg Gratings (FBGs), integrated at several positions along the optical fiber. FBGs are in-fiber sensors that are multiplexed. lt is possible to place hundreds of FBG sensors along one single fiber, thus allowing for quasidistributed sensing of temperature or strain. The optical fiber itself can be less than 100 micrometer in diameter, allowing for sensing at several points in a minimally invasive way, when integrated in a tool or component.
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11.
  • Dihge, Looket, et al. (författare)
  • Artificial neural network models to predict nodal status in clinically node-negative breast cancer
  • 2019
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Sentinel lymph node biopsy (SLNB) is standard staging procedure for nodal status in breast cancer, but lacks therapeutic benefit for patients with benign sentinel nodes. For patients with positive sentinel nodes, individualized surgical strategies are applied depending on the extent of nodal involvement. Preoperative prediction of nodal status is thus important for individualizing axillary surgery avoiding unnecessary surgery. We aimed to predict nodal status in clinically node-negative breast cancer and identify candidates for SLNB omission by including patient-related and pathological characteristics into artificial neural network (ANN) models. Methods: Patients with primary breast cancer were consecutively included between January 1, 2009 and December 31, 2012 in a prospectively maintained pathology database. Clinical- and radiological data were extracted from patient's files and only clinically node-negative patients constituted the final study cohort. ANN-based models for nodal prediction were constructed including 15 risk variables for nodal status. Area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness-of-fit test (HL) were used to assess performance and calibration of three predictive ANN-based models for no lymph node metastasis (N0), metastases in 1-3 lymph nodes (N1) and metastases in ≥ 4 lymph nodes (N2). Linear regression models for nodal prediction were calculated for comparison. Results: Eight hundred patients (N0, n = 514; N1, n = 232; N2, n = 54) were included. Internally validated AUCs for N0 versus N+ was 0.740 (95% CI = 0.723-0.758); median HL was 9.869 (P = 0.274), for N1 versus N0, 0.705 (95% CI = 0.686-0.724; median HL: 7.421; P = 0.492) and for N2 versus N0 and N1, 0.747 (95% CI = 0.728-0.765; median HL: 9.220; P = 0.324). Tumor size and vascular invasion were top-ranked predictors of all three end-points, followed by estrogen receptor status and lobular cancer for prediction of N2. For each end-point, ANN models showed better discriminatory performance than multivariable logistic regression models. Accepting a false negative rate (FNR) of 10% for predicting N0 by the ANN model, SLNB could have been abstained in 27.25% of patients with clinically node-negative axilla. Conclusions: In this retrospective study, ANN showed promising result as decision-supporting tools for estimating nodal disease. If prospectively validated, patients least likely to have nodal metastasis could be spared SLNB using predictive models. Trial registration: Registered in the ISRCTN registry with study ID ISRCTN14341750. Date of registration 23/11/2018. Retrospectively registered.
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12.
  • Dihge, Looket, et al. (författare)
  • The implementation of NILS : A web-based artificial neural network decision support tool for noninvasive lymph node staging in breast cancer
  • 2023
  • Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To implement artificial neural network (ANN) algorithms for noninvasive lymph node staging (NILS) to a decision support tool and facilitate the option to omit surgical axillary staging in breast cancer patients with low-risk of nodal metastasis. Methods: The NILS tool is a further development of an ANN prototype for the prediction of nodal status. Training and internal validation of the original algorithm included 15 clinical and tumor-related variables from a consecutive cohort of 800 breast cancer cases. The updated NILS tool included 10 top-ranked input variables from the original prototype. A workflow with four ANN pathways was additionally developed to allow different combinations of missing preoperative input values. Predictive performances were assessed by area under the receiver operating characteristics curves (AUC) and sensitivity/specificity values at defined cut-points. Clinical utility was presented by estimating possible sentinel lymph node biopsy (SLNB) reduction rates. The principles of user-centered design were applied to develop an interactive web-interface to predict the patient’s probability of healthy lymph nodes. A technical validation of the interface was performed using data from 100 test patients selected to cover all combinations of missing histopathological input values. Results: ANN algorithms for the prediction of nodal status have been implemented into the web-based NILS tool for personalized, noninvasive nodal staging in breast cancer. The estimated probability of healthy lymph nodes using the interface showed a complete concordance with estimations from the reference algorithm except in two cases that had been wrongly included (ineligible for the technical validation). NILS predictive performance to distinguish node-negative from node-positive disease, also with missing values, displayed AUC ranged from 0.718 (95% CI, 0.687-0.748) to 0.735 (95% CI, 0.704-0.764), with good calibration. Sensitivity 90% and specificity 34% were demonstrated. The potential to abstain from axillary surgery was observed in 26% of patients using the NILS tool, acknowledging a false negative rate of 10%, which is clinically accepted for the standard SLNB technique. Conclusions: The implementation of NILS into a web-interface are expected to provide the health care with decision support and facilitate preoperative identification of patients who could be good candidates to avoid unnecessary surgical axillary staging.
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14.
  • Figuero, Elena, et al. (författare)
  • Quantification of Periodontal Pathogens in Vascular, Blood, and Subgingival Samples From Patients With Peripheral Arterial Disease or Abdominal Aortic Aneurysms
  • 2014
  • Ingår i: Journal of Periodontology. - : American Academy of Peridontology. - 0022-3492 .- 1943-3670. ; 85:9, s. 1182-1193
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this investigation is to quantify periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, and Tannerella forsythia) in vascular, blood, and subgingival samples. As a secondary objective, two molecular bacterial identification methods (nested polymerase chain reaction [PCR] and quantitative PCR [qPCR]) are compared. Methods: Seventy consecutive patients provided a vascular lesion, a blood sample, and 36 subgingival samples. Bacterial DNA was extracted, and qPCR was used to determine the prevalence and amounts of the target pathogens in each sample. Nested PCR was performed only in the samples from vascular lesions. Periodontal examination was performed in 42 patients. Mann-Whitney U or x(2) tests were used to compare microbiologic results according to periodontal diagnosis. Results: All targeted periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, T. forsythia, or C. rectus) were detected in subgingival samples, with a prevalence rate of 72.2%, 47.2%, 74.3%, and 82.9%, respectively. In 7.1% and 11.4% of vascular and blood samples, bacterial DNA was detected. One patient was positive for A. actinomycetemcomitans in the three types of samples. No differences were found in the levels of targeted bacteria when comparing patients with and without periodontitis. Prevalence rates obtained with nested PCR were significantly higher than those obtained with qPCR. Conclusions: The presence of A. actinomycetemcomitans was demonstrated in vascular, blood, and subgingival samples in one of 36 patients. These results, although with a very low frequency, may support the hypothesis of a translocation of periodontal pathogens from subgingival microbiota to the bloodstream and then to atheromatous plaques in carotid or other peripheral arteries. Nested PCR is not an adequate method for identifying DNA of periodontal pathogens in low quantities because of the high number of false-negative results.
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15.
  • Forsberg, Per Ola, et al. (författare)
  • Causal nature of neighborhood deprivation on individual risk of coronary heart disease or ischemic stroke : A prospective national Swedish co-relative control study in men and women
  • 2018
  • Ingår i: Health and Place. - : Elsevier BV. - 1353-8292. ; 50, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the association between neighborhood socioeconomic status (SES) and incidence of coronary heart disease (CHD) or ischemic stroke in the total population and in full- and half-siblings to determine whether these associations are causal or a result from familial confounding. Data were retrieved from nationwide Swedish registers containing individual clinical data linked to neighborhood of residence. After adjustment for individual SES, the association between neighborhood SES and CHD showed no decrease with increasing genetic resemblance, particularly in women. This indicates that the association between neighborhood SES and CHD incidence is partially causal among women, which represents a novel finding.
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16.
  • Forsberg, Per Ola, et al. (författare)
  • Workplace socioeconomic characteristics and coronary heart disease : a nationwide follow-up study
  • 2023
  • Ingår i: BMJ Open. - 2044-6055. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Important gaps in previous research include a lack of studies on the association between socioeconomic characteristics of the workplace and coronary heart disease (CHD). We aimed to examine two contextual factors in association with individuals' risk of CHD: the mean educational level of all employees at each individual's workplace (education work) and the neighbourhood socioeconomic characteristics of each individual's workplace (neighbourhood SES work). Design Nationwide follow-up/cohort study. Setting Nationwide data from Sweden. Participants All individuals born in Sweden from 1943 to 1957 were included (n=1 547 818). We excluded individuals with a CHD diagnosis prior to 2008 (n=67 619), individuals without workplace information (n=576 663), individuals lacking residential address (n=4139) and individuals who had unknown parents (n=7076). A total of 892 321 individuals were thus included in the study (426 440 men and 465 881 women). Primary and secondary outcome measures The outcome variable was incident CHD during follow-up between 2008 and 2012. The association between education work and neighbourhood SES work and the outcome was explored using multilevel and cross-classified logistic regression models to determine ORs and 95% CIs, with individuals nested within workplaces and neighbourhoods. All models were conducted in both men and women and were adjusted for age, income, marital status, educational attainment and neighbourhood SES residence. Results Low (vs high) education work was significantly associated with increased CHD incidence for both men (OR 1.29, 95% CI 1.23 to 1.34) and women (OR 1.38, 95% CI 1.29 to 1.47) and remained significant after adjusting for potential confounders. These findings were not replicable for the variable neighbourhood SES work. Conclusions Workplace socioeconomic characteristics, that is, the educational attainment of an individual's colleagues, may influence CHD risk, which represents new knowledge relevant to occupational health management at workplaces.
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18.
  • Ghali, Jalal K, et al. (författare)
  • The influence of renal function on clinical outcome and response to beta-blockade in systolic heart failure: insights from Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF).
  • 2009
  • Ingår i: Journal of cardiac failure. - : Elsevier BV. - 1532-8414 .- 1071-9164. ; 15:4, s. 310-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Limited information is available on the risk and impact of renal dysfunction on the response to beta-blockade and mode of death in systolic heart failure (HF). METHODS AND RESULTS: Renal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR(MDRD) > 60 (n = 2496), eGFR(MDRD) 45 to 60 (n = 976), and eGFR(MDRD) < 45 mL/min per 1.73 m(2) body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups. CONCLUSIONS: Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60.
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19.
  • Gunnlaugsson, Adalsteinn, et al. (författare)
  • A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and Ga-68-PSMA-PET for biochemical relapse after radical prostatectomy-The PROPER 1 trial
  • 2022
  • Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 77-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still >= 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.
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20.
  • Gustafsson, Rita, et al. (författare)
  • Esophageal Dysmotility is More Common Than Gastroparesis in Diabetes Mellitus and is Associated With Retinopathy.
  • 2011
  • Ingår i: Review of Diabetic Studies. - 1614-0575. ; 8:2, s. 268-275
  • Tidskriftsartikel (refereegranskat)abstract
    • Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic and asymptomatic patients. Esophageal dysmotility has also been described, but is not as well-characterized. The etiology and effect of these complications need to be clarified. The aim of the present study was to evaluate esophageal and gastric motility, complications, gastrointestinal symptoms, and plasma biomarkers in a cross-sectional study comprising patients with diabetes mellitus.
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21.
  • Hall, Ola, et al. (författare)
  • A review of explainable AI in the satellite data, deep machine learning, and human poverty domain
  • 2022
  • Ingår i: Patterns. - Cambridge : Cell Press. - 2666-3899. ; 3:10
  • Forskningsöversikt (refereegranskat)abstract
    • Recent advances in artificial intelligence and deep machine learning have created a step change in how to measure human development indicators, in particular asset-based poverty. The combination of satellite imagery and deep machine learning now has the capability to estimate some types of poverty at a level close to what is achieved with traditional household surveys. An increasingly important issue beyond static estimations is whether this technology can contribute to scientific discovery and, consequently, new knowledge in the poverty and welfare domain. A foundation for achieving scientific insights is domain knowledge, which in turn translates into explainability and scientific consistency. We perform an integrative literature review focusing on three core elements relevant in this context—transparency, interpretability, and explainability—and investigate how they relate to the poverty, machine learning, and satellite imagery nexus. Our inclusion criteria for papers are that they cover poverty/wealth prediction, using survey data as the basis for the ground truth poverty/wealth estimates, be applicable to both urban and rural settings, use satellite images as the basis for at least some of the inputs (features), and the method should include deep neural networks. Our review of 32 papers shows that the status of the three core elements of explainable machine learning (transparency, interpretability, and domain knowledge) is varied and does not completely fulfill the requirements set up for scientific insights and discoveries. We argue that explainability is essential to support wider dissemination and acceptance of this research in the development community and that explainability means more than just interpretability. (c) 2022 The Author(s). 
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22.
  • Henriksson, Eva, et al. (författare)
  • Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck
  • 2009
  • Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test ( crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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23.
  • Hjärtström, Malin, et al. (författare)
  • Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning : External Validation and Further Model Development
  • 2023
  • Ingår i: JMIR Cancer. - Toronto, ON : JMIR Publications. - 2369-1999. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using postoperative data or imaging features that are not part of the diagnostic workup. Lymphovascular invasion (LVI) is a top-ranked predictor of nodal metastasis; however, its preoperative assessment is challenging.Objective: This paper aimed to externally validate a multilayer perceptron (MLP) model for noninvasive lymph node staging (NILS) in a large population-based cohort (n=18,633) and develop a new MLP in the same cohort. Data were extracted from the Swedish National Quality Register for Breast Cancer (NKBC, 2014-2017), comprising only routinely and preoperatively available documented clinicopathological variables. A secondary aim was to develop and validate an LVI MLP for imputation of missing LVI status to increase the preoperative feasibility of the original NILS model. Methods: Three nonoverlapping cohorts were used for model development and validation. A total of 4 MLPs for nodal status and 1 LVI MLP were developed using 11 to 12 routinely available predictors. Three nodal status models were used to account for the different availabilities of LVI status in the cohorts and external validation in NKBC. The fourth nodal status model was developed for 80% (14,906/18,663) of NKBC cases and validated in the remaining 20% (3727/18,663). Three alternatives for imputation of LVI status were compared. The discriminatory capacity was evaluated using the validation area under the receiver operating characteristics curve (AUC) in 3 of the nodal status models. The clinical feasibility of the models was evaluated using calibration and decision curve analyses.Results: External validation of the original NILS model was performed in NKBC (AUC 0.699, 95% CI 0.690-0.708) with good calibration and the potential of sparing 16% of patients with node-negative disease from SLNB. The LVI model was externally validated (AUC 0.747, 95% CI 0.694-0.799) with good calibration but did not improve the discriminatory performance of the nodal status models. A new nodal status model was developed in NKBC without information on LVI (AUC 0.709, 95% CI: 0.688-0.729), with excellent calibration in the holdout internal validation cohort, resulting in the potential omission of 24% of patients from unnecessary SLNBs.Conclusions: The NILS model was externally validated in NKBC, where the imputation of LVI status did not improve the model's discriminatory performance. A new nodal status model demonstrated the feasibility of using register data comprising only the variables available in the preoperative setting for NILS using machine learning. Future steps include ongoing preoperative validation of the NILS model and extending the model with, for example, mammography images. © Malin Hjärtström, Looket Dihge, Pär-Ola Bendahl, Ida Skarping, Julia Ellbrant, Mattias Ohlsson, Lisa Rydén.
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24.
  • Hössjer, Ola, et al. (författare)
  • Assessing individual unexplained variation in non-life insurance.
  • 2009
  • Ingår i: Astin Bulletin. - 0515-0361 .- 1783-1350. ; 39:1, s. 249-273
  • Tidskriftsartikel (refereegranskat)abstract
    • We consider variation of observed claim frequencies in non-life insurance, modeled by Poisson regression with overdispersion. In order to quantify how much variation between insurance policies that is captured by the rating factors, one may use the coefficient of determination, R2, the estimated proportion of total variation explained by the model. We introduce a novel coefficient of individual determination (CID), which excludes noise variance and is defined as the estimated fraction of total individual variation explained by the model. We argue that CID is a more relevant measure of explained variation than R2 for data with Poisson variation. We also generalize previously used estimates and tests of overdispersion and introduce new coefficients of individual explained and unexplained variance.Application to a Swedish three year motor TPL data set reveals that only 0.5% of the total variation and 11% of the total individual variation is explained by a model with seven rating factors, including interaction between sex and age. Even though the amount of overdispersion is small (4.4% of the noise variance) it is still highly significant. The coefficient of variation of explained and unexplained individual variation is 29% and 81% respectively.
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25.
  • Isaksson, Ola, 1969, et al. (författare)
  • The Importance of Digitalisation in Industrialising Additive Manufacturing: Learnings from the DIDAM P2030 Project
  • 2024
  • Ingår i: Advances in Transdisciplinary Engineering. - : IOS Press BV. - 2352-751X .- 2352-7528. ; 52, s. 442-452
  • Konferensbidrag (refereegranskat)abstract
    • Additive manufacturing, a technology that has evolved significantly over the last few decades, has shifted from prototyping to final product manufacturing. Despite its potential in design flexibility and customisation, its implementation in industrial ecosystems often faces challenges, especially in companies with established traditional manufacturing methods. This paper explores additive manufacturing beyond the printing process, drawing insights from the DIDAM project in Swedish manufacturing companies. It maps the advantages of additive manufacturing to external factors influencing its success such as digital infrastructure. This mapping yields “risk factors” for its implementation. These factors are based on empirical observations from the DIDAM project to identify potential failure modes, assess risks, and provide a snapshot view of critical issues. This objective evaluation aims to support managers in evaluating the risks associated with additive manufacturing’s integration into a company’s manufacturing ecosystem, based on empirical findings in industrial cases as reported in the DIDAM Digital Model Guide (Digital Model Guide, 2023).
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26.
  • Janson, Peter C. J., et al. (författare)
  • CpG methylation of the IFNG gene as a mechanism to induce immunosupression in tumor-infiltrating lymphocytes
  • 2008
  • Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 181:4, s. 2878-2886
  • Tidskriftsartikel (refereegranskat)abstract
    • The execution of appropriate gene expression patterns during immune responses is of eminent importance where CpG methylation has emerged as an essential mechanism for gene silencing. We have charted the methylation status of regulatory elements in the human IFNG gene encoding the signature cytokine of the Th1 response. Surprisingly, human naive CD4(+) T lymphocytes displayed hypermethylation at the IFNG promoter region, which is in sharp contrast to the completely demethylated status of this region in mice. Th1 differentiation induced demethylation of the IFNG promoter and the upstream conserved nucleotide sequence 1 enhancer region, whereas Th2-differentiated lymphocytes remained hypermethylated. Furthermore, CD19(+) B lymphocytes displayed hypomethylation at the IFNG promoter region with a similar pattern to Th1 effector cells. When investigating the methylation status among tumor-infiltrating CD4(+) T lymphocytes from patients with colon cancer, we found that tumor-infiltrating lymphocytes cells are inappropriately hypermethylated, and thus not confined to the Th1 lineage. In contrast, CD4(+) T cells from the tumor draining lymph node were significantly more demethylated than tumor-infiltrating lymphocytes. We conclude that there are obvious interspecies differences in the methylation status of the IFNG gene in naive CD4(+) T lymphocytes, where Th1 commitment in human lymphocytes involves demethylation before IFNG expression. Finally, investigations of tumor-infiltrating lymphocytes and CD4(+) cells from tumor draining lymph node demonstrate methylation of regulatory regions within key effector genes as an epigenetic mechanism of tumor-induced immunosupression.
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27.
  • Janson, Peter C. J., et al. (författare)
  • FOXP3 Promoter Demethylation Reveals the Committed Treg Population in Humans
  • 2008
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:2, s. e1612-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Naturally occurring thymus derived regulatory T cells (Tregs) are central in the maintenance of self-tolerance. The transcription factor FOXP3 is crucial for the suppressive activity of Tregs and is considered the most specific marker for this population. However, human non regulatory T cells upregulate FOXP3 transiently upon activation which calls for other means to identify the Treg population. Since epigenetic mechanisms are involved in the establishment of stable gene expression patterns during cell differentiation, we hypothesized that the methylation profile of the FOXP3 promoter would allow the distinction of truly committed Tregs. Methodology/Principal Findings: Human CD4(+) CD25(hi) Tregs displayed a demethylated FOXP3 promoter (1.4%+/-0.95% SEM methylated) in contrast to CD4(+) CD25(lo) T cells which were partially methylated (27.9%+/-7.1%). Furthermore, stimulated CD4(+)CD25(lo) T cells transiently expressed FOXP3 but remained partially methylated, suggesting promoter methylation as a mechanism for regulation of stable FOXP3 expression and Treg commitment. In addition, transient FOXP3 expressing cells exhibited suppressive abilities that correlate to the methylation status of the FOXP3 promoter. As an alternative to bisulphite sequencing, we present a restriction enzyme based screening method for the identification of committed Tregs and apply this method to evaluate the effect of various culturing conditions. We show that a partial demethylation occurs in long-term cultures after activation, whereas the addition of TGF-beta and/or IL-10 does not induce any additional change in methylation level. Conclusions/Significance: The unique FOXP3 promoter methylation profile in Tregs suggests that a demethylated pattern is a prerequisite for stable FOXP3 expression and suppressive phenotype. Presently, FOXP3 is used to identify Tregs in several human diseases and there are future implications for adoptive Treg transfer in immunotherapy. In these settings there is a need to distinguish true Tregs from transiently FOXP3(+) activated T cells. The screening method we present allows this distinction and enables the identification of cells suitable for in vitro expansions and clinical use.
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28.
  • Kalderstam, Jonas, et al. (författare)
  • Training artificial neural networks directly on the concordance index for censored data using genetic algorithms.
  • 2013
  • Ingår i: Artificial Intelligence in Medicine. - : Elsevier BV. - 1873-2860 .- 0933-3657. ; 58:2, s. 125-132
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The concordance index (c-index) is the standard way of evaluating the performance of prognostic models in the presence of censored data. Constructing prognostic models using artificial neural networks (ANNs) is commonly done by training on error functions which are modified versions of the c-index. Our objective was to demonstrate the capability of training directly on the c-index and to evaluate our approach compared to the Cox proportional hazards model. METHOD: We constructed a prognostic model using an ensemble of ANNs which were trained using a genetic algorithm. The individual networks were trained on a non-linear artificial data set divided into a training and test set both of size 2000, where 50% of the data was censored. The ANNs were also trained on a data set consisting of 4042 patients treated for breast cancer spread over five different medical studies, 2/3 used for training and 1/3 used as a test set. A Cox model was also constructed on the same data in both cases. The two models' c-indices on the test sets were then compared. The ranking performance of the models is additionally presented visually using modified scatter plots. RESULTS: Cross validation on the cancer training set did not indicate any non-linear effects between the covariates. An ensemble of 30 ANNs with one hidden neuron was therefore used. The ANN model had almost the same c-index score as the Cox model (c-index=0.70 and 0.71, respectively) on the cancer test set. Both models identified similarly sized low risk groups with at most 10% false positives, 49 for the ANN model and 60 for the Cox model, but repeated bootstrap runs indicate that the difference was not significant. A significant difference could however be seen when applied on the non-linear synthetic data set. In that case the ANN ensemble managed to achieve a c-index score of 0.90 whereas the Cox model failed to distinguish itself from the random case (c-index=0.49). CONCLUSIONS: We have found empirical evidence that ensembles of ANN models can be optimized directly on the c-index. Comparison with a Cox model indicates that near identical performance is achieved on a real cancer data set while on a non-linear data set the ANN model is clearly superior.
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29.
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30.
  • Kindblom, Jenny, 1971, et al. (författare)
  • Pubertal Body Mass Index Change Is Associated With Adult Coronary Atherosclerosis and Acute Coronary Events in Men
  • 2021
  • Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 41:8, s. 2318-2327
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim with the present study was to evaluate the association between pubertal body mass index (BMI) change and adult coronary artery calcification (CAC) score and risk of acute coronary events. Approach and Results: We included 37 672 men from the BMI Epidemiology Study and calculated their pubertal BMI change (BMI at 20 years-BMI at 8 years). Coronary artery computed tomography analysis of CAC score, midlife BMI, and major risk factors for coronary heart disease were available for a sub-cohort through linkage with the SCAPIS (Swedish Cardio Pulmonary Bioimage Study) cohort (n=922). Information on first acute coronary events was retrieved from Swedish national registers (n=37 672, events n=1873). Pubertal BMI change (odds ratio per SD increase, 1.32 [1.14-1.52]), but not childhood BMI, was associated with middle age CAC score >= 1. This association for pubertal BMI change was maintained after adjustment for midlife BMI at CAC analysis and in a model including major cardiovascular risk factors. Individuals who became overweight during puberty (hazard ratio, 2.11 [1.79-2.49]), but not those overweight at 8 years who normalized their weight during puberty, had substantially increased risk of acute coronary events compared with men who were never overweight. Among subjects with an acute coronary event, individuals with pubertal onset overweight were at increased risk of death due to the event. Conclusions: Pubertal BMI change is an independent predictor of CAC score and risk of acute coronary events in adult men. Excessive BMI increase during puberty may initiate the coronary atherosclerotic process, thereby increasing the risk and severity of adult acute coronary events.
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31.
  • Kjölhede, Henrik, et al. (författare)
  • (18)F-choline PET/CT for early detection of metastases in biochemical recurrence following radical prostatectomy.
  • 2015
  • Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 33:11, s. 1749-1752
  • Tidskriftsartikel (refereegranskat)abstract
    • Salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) should if possible be added at a prostate-specific antigen (PSA) level of <1-2 ng/mL. The value of positron emission tomography combined with computed tomography (PET/CT) at such low PSA values is not defined. The purpose was to determine what proportion of a well-defined cohort of hormone-naïve patients who were candidates for early salvage radiotherapy had (18)F-choline PET/CT findings suggesting metastases.
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32.
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33.
  • Kjölhede, Henrik, et al. (författare)
  • Combined (18) F-fluorocholine and (18) F-fluoride positron emission tomography/computed tomography imaging for staging of high-risk prostate cancer.
  • 2012
  • Ingår i: BJU International. - 1464-4096. ; 110:10, s. 1501-1506
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Type - Diagnosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Positron emission tomography/computed tomography (PET/CT) with choline and fluoride for the detection of metastases in patients with prostate cancer have each been evaluated, with mixed results. Choline PET/CT has been evaluated against pelvic lymphadenectomy, generally with a low sensitivity but a high specificity; however, the study populations have been heterogenous. Fluoride PET/CT has been evaluated against other imaging methods, such as bone scan, single photon emission CT and MRI, and has been shown to have high specificity as well as sensitivity for bone metastases, but there are no studies with biopsy verification. This is the first study that evaluates the clinical use of both choline and fluoride PET/CT on the same patients in a well-defined population of patients with high-risk prostate cancer. OBJECTIVE: • To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both (18) F-fluorocholine and (18) F-fluoride as markers, add clinically relevant information for patients with prostate cancer who have high-risk tumours and a normal or inconclusive planar bone scan. PATIENTS AND METHODS: • Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8-10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a (18) F-fluorocholine and a (18) F-fluoride PET/CT. • None of the patients received hormonal therapy before the staging procedures were completed. RESULTS: • For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases. • (18) F-fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%). • (18) F-fluoride PET/CT was suggestive for bone metastases in 37 patients (41%). • In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non-curative. • Of the patients with positive scans, 74% had Gleason score 8-10 tumours. Of the patients with Gleason score 8-10 tumours, 64% had positive scans. CONCLUSIONS: • PET/CT scans with (18) F-fluorocholine and (18) F-fluoride commonly detect metastases in patients with high-risk prostate cancer and a negative or inconclusive bone scan. • For 20% of the patients the results of the PET/CT scans changed the treatment plan.
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34.
  • Lindén, Ola, et al. (författare)
  • 131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing chemotherapy. Treatment outcome, haematological toxicity and bone marrow absorbed dose estimates.
  • 2002
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 297-303
  • Tidskriftsartikel (refereegranskat)abstract
    • The experience with radioimmunotherapy in B-cell lymphomas using the rapidly internalizing antibody, anti-CD22 (LL2), is limited. In this study we investigated the efficacy and toxicity of 131I-labelled-LL2 for radioimmunotherapy in patients with B-cell lymphomas that failed one or two cytostatic regimens. Eleven patients were treated with one or repeated cycles of 131I-anti-CD22 antibody, 1330 MBq/m2 (36 mCi/m2). Six of the 11 treated patients demonstrated an objective response, three of them with complete remission. All follicular (3 patients) and transformed lymphomas (2 patients) responded compared to one of four diffuse large B-cell lymphomas. Two out of six responders exhibited event-free survival (EFS), which was comparable with or longer than the EFS following primary anthracycline-containing chemotherapy. Non-haematological toxicity was mild. Haematological toxicity was associated with pretreatment clinical characteristics but not with estimated absorbed bone marrow doses. Objective remission following treatment with 131I-anti-CD22 can be achieved in patients with various subtypes of B-cell lymphomas, failing standard chemotherapy. Follicular or transformed lymphomas seem particularly responsive. Haematological toxicity seems to be dependent on the functional status of the bone marrow before radioimmunotherapy.
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35.
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36.
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37.
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38.
  • Lindén, Ola, et al. (författare)
  • Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas
  • 1999
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; 5:10 Suppl, s. 3287-3291
  • Tidskriftsartikel (refereegranskat)abstract
    • Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.
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39.
  • Nielsen, Magnus, et al. (författare)
  • Interpretation of captopril renography using artificial neural networks
  • 2005
  • Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:5, s. 293-296
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to develop a method based on artificial neural networks for interpretation of captopril renography tests for the detection of renovascular hypertension caused by renal artery stenosis and to assess the value of different measurements from the test. A total of 250 99mTc-MAG3 captopril renography tests were used in the study. The material was collected from two different patient groups. One group consisted of 101 patients who also had undergone a renal angiography. The angiographies, which were used as gold standard, showed a significant renal artery stenosis in 53 of the 101 cases. The second group consisted of 149 patients, who's captopril renography tests all were interpreted as not compatible with significant renal artery stenosis by an experienced nuclear medicine physician. Artificial neural networks were trained for the diagnosis of renal artery stenosis using eight measures from each renogram. The neural network was then evaluated in separate test groups using an eightfold cross validation procedure. The performance of the neural networks, measured as the area under the receiver operating characteristic curve, was 0.93. The sensitivity was 91% at a specificity of 90%. The lowest performance was found for the network trained without use of a parenchymal transit measure, indicating the importance of this feature. Artificial neural networks can be trained to interpret captopril renography tests for detection of renovascular hypertension caused by renal artery stenosis. The result almost equals that of human experts shown in previous studies. © 2005 Blackwell Publishing Ltd.
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40.
  • Nielsen, Magnus, et al. (författare)
  • Interpretation of captopril renography using artificial neural networks.
  • 2005
  • Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 25:5, s. 293-296
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to develop a method based on artificial neural networks for interpretation of captopril renography tests for the detection of renovascular hypertension caused by renal artery stenosis and to assess the value of different measurements from the test. A total of 250 99mTc-MAG3 captopril renography tests were used in the study. The material was collected from two different patient groups. One group consisted of 101 patients who also had undergone a renal angiography. The angiographies, which were used as gold standard, showed a significant renal artery stenosis in 53 of the 101 cases. The second group consisted of 149 patients, who's captopril renography tests all were interpreted as not compatible with significant renal artery stenosis by an experienced nuclear medicine physician. Artificial neural networks were trained for the diagnosis of renal artery stenosis using eight measures from each renogram. The neural network was then evaluated in separate test groups using an eightfold cross validation procedure. The performance of the neural networks, measured as the area under the receiver operating characteristic curve, was 0.93. The sensitivity was 91% at a specificity of 90%. The lowest performance was found for the network trained without use of a parenchymal transit measure, indicating the importance of this feature. Artificial neural networks can be trained to interpret captopril renography tests for detection of renovascular hypertension caused by renal artery stenosis. The result almost equals that of human experts shown in previous studies.
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41.
  • Ohlsson, Bodil, et al. (författare)
  • Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis.
  • 2006
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 49:2006 Jul 11, s. 2010-2014
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Among diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis. Materials and methods Oesophageal manometry and gastric emptying scintigraphy were performed in 20 diabetic patients. Heart-rate variation during deep breathing (expiration/inspiration [E/I] ratio) and continuous subcutaneous glucose concentrations for a period of 72 h were also monitored in the same patients. Results Oesophageal dysmotility was found in eight of 14 patients. Eleven of 20 patients had delayed gastric emptying (abnormal gastric emptying half-time [T (50)]) and nine of 18 had an abnormal E/I ratio. Complaints of abdominal fullness were predictive of delayed gastric emptying. A low peristaltic speed of the oesophagus was associated with impaired T (50) (r (s) =-0.67; p=0.02). One hour after breakfast, subcutaneous glucose levels decreased in patients with delayed gastric emptying but continued to rise in those with normal emptying. Consequently, the median glucose level 2.5 h after breakfast was lower in the former (9.1 [4.2-12.5] vs 14.3 [11.2-17.7] mmol/l; p < 0.05). Glucose fluctuations during the 72 h were significantly higher in patients with an abnormal E/I ratio than in those with a normal E/I ratio (coefficient of variation: 41 [46-49] vs 28 [27-34]%; p=0.008). Conclusions/interpretation Abdominal fullness predicted delayed gastric emptying that was associated with diminished glucose uptake after breakfast. Low oesophageal peristaltic speed was associated with slow gastric emptying whereas parasympathetic neuropathy was associated with increased glucose variations.
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42.
  • Ohlsson, Bodil, et al. (författare)
  • The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human
  • 2006
  • Ingår i: BMC Gastroenterology. - 1471-230X. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying. METHODS: Ten healthy volunteers (five men) were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockage of the oxytocin receptors (which also blocks the vasopressin receptors) and thereby inhibiting physiological doses of oxytocin; and once during saline infusion. Gastric emptying rate (GER) was assessed and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after ingestion of rice pudding. The assessment was performed by real-time ultrasonography. At the same time, the feeling of satiety was registered using visual satiety scores. RESULTS: Inhibition of the binding of endogenous oxytocin by the receptor antagonist delayed the GER by 37 % compared to saline (p = 0.037). In contrast, infusion of oxytocin in a dosage of 40 mU/min did not affect the GER (p = 0.610). Satiation scores areas in healthy subjects after receiving atosiban or oxytocin did not show any significant differences. CONCLUSION: Oxytocin and/or vasopressin seem to be regulators of gastric emptying during physiological conditions, since the receptor antagonist atosiban delayed the GER. However, the actual pharmacological dose of oxytocin in this study had no effect. The effect of oxytocin and vasopressin on GI motility has to be further evaluated.
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43.
  • Ohlsson, Håkan, et al. (författare)
  • Assessment of the surgical apgar score in a Swedish setting
  • 2011
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 55:5, s. 524-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Predicting major post-operative complications is an important task for which simple and reliable methods are lacking. A simple scoring system based on intraoperative heart rate, blood pressure and blood loss was recently developed to fill this gap. This system, the Surgical Apgar Score, shows promising results both in terms of validity and in terms of usefulness. The goal of this study was to study both these components in a Scandinavian setting.Methods: Pre-operative patient characteristics and intraoperative variables were recorded for 224 patients undergoing general and vascular surgery between 26 October and 17 December 2009. Major complications were evaluated during a 30-day follow-up. The relationship between Surgical Apgar Score and major complication was analysed using chi(2) -tests and the relative risk between different scoring patient groups was analysed.Results: The study showed a strong correlation between the Surgical Apgar Score and major complication (P<0.001). 61.5% of the lowest-scoring patients sustained a major complication compared with only 6.4% in the highest-scoring group. This is equivalent to a relative risk of 7.14 (95% CI: 2.88-17.5, P<0.001).Conclusions: The Surgical Apgar Score is valid in a Scandinavian setting. We also note that there were no practical issues in collecting the score. Together with patient pre-operative risk, the score has great potential to guide clinicians when making post-operative decisions and give immediate feedback about the surgical procedure. The next step should be to educate surgical staff about the score.
  •  
44.
  • Ohlsson, Lars Ola, et al. (författare)
  • Evaluation of Laminaria digitata and Phragmites australis for biogas production and nutrient recycling
  • 2020
  • Ingår i: Biomass and Bioenergy. - : Elsevier BV. - 1873-2909 .- 0961-9534. ; 140
  • Tidskriftsartikel (refereegranskat)abstract
    • Eutrophication and climate change are major global problems. The sea weed Laminaria digitata and the reed Phragmites australis have the potential to absorb nutrients and CO2 during growth, as well as being a source of renewable energy in the form of biogas. The aim of this study was to evaluate Laminaria digitata and Phragmites australis concerning biogas production and nutrient recycling using a two-stage pilot scale process. The plant has a total volume of 430 L and consists of a hydrolysis bed and an up-flow anaerobic sludge blanket reactor (UASB). Two experiments were performed; one with Laminaria digitata as the sole substrate and one with a mixture of Laminaria digitata and Phragmites australis. Frozen substrates were placed in the hydrolysis bed and digestion was performed at 305 K during 70 days for Laminaria digitata and 100 days for the mixture of Laminaria digitata and Phragmites australis. The methane yield achieved was approximately 170 L kg−1 volatile substances (273.15 K, 101.3 kPa) in both experiments. These results suggest that Laminaria digitata can be efficiently digested in larger scale and has the potential to contribute to a future sustainable energy mix, considering its relatively high methane yield when anaerobically digested as the sole substrate. Digestion of Phragmites australis needs further development to make use of its full potential.
  •  
45.
  • Ohlsson, Ola, et al. (författare)
  • Inventering av mykorrhiza i potatisförsök
  • 2011
  • Ingår i: LTJ-fakultetens faktablad. - Alnarp : Fakulteten för landskapsplanering, trädgårds- och jordbruksvetenskap, Sveriges lantbruksuniversitet.
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Symbios med mykorrhizabildande svampar förekommer hos de flesta landlevande växter. Växter med mykorrhiza har ofta en bättre upptagning av fosfor (P) när tillgången på fosfor är låg. Mykorrhizabildningen i värdväxtens rötter kan emellertid hämmas när det är god tillgång på fosfor. Under 2010 undersöktes förekomsten av mykorrhiza i två försök där potatis odlades vid olika fosfornivåer. Ingen mykorrhizakolonisering kunde påvisas vid mikroskopering av rötterna i något av försöken. Halten av lättillgänglig fosfor i marken varierade från en hög P-AL klass III till klass V.
  •  
46.
  • Pendleton, Hillevi, et al. (författare)
  • Posterior laryngitis: a disease with different aetiologies affecting health-related quality of life:a prospective case–control study
  • 2013
  • Ingår i: BMC Ear, Nose and Throat Disorders. - : Springer Science and Business Media LLC. - 1472-6815. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Laryngo-pharyngeal reflux (LPR) is assumed to be the most common cause of posterior laryngitis (PL). Since LPR is found in healthy subjects, and PL patients are not improved by acid-reducing therapy, other aetiologies to PL must be considered. The aims of this study in PL were to investigate the prevalence of acid reflux in the proximal oesophagus and functional gastrointestinal symptoms, to analyse motilin levels in plasma, and to assess health-related quality of life (HRQOL) before and after treatment. Methods: Forty-six patients (26 women), with verified PL, median age 55 (IQR 41–68) years, were referred to oesophago-gastro-duodenoscopy and 24-h pH monitoring. Plasma motilin was analysed. The 36-item Short-Form questionnaire was completed at inclusion and at follow-up after 43±14 months, when also the Visual Analogue Scale for Irritable Bowel Syndrome was completed. Values were compared to controls. Treatment and relief of symptoms were noted from medical records. Results: Thirty-four percent had proximal acid reflux and 40% showed signs of distal reflux. Ninety-four percent received acid-reducing treatment, with total relief of symptoms in 17%. Patients with reflux symptoms had lower plasma motilin levels compared to patients without reflux symptoms (p = 0.021). The HRQOL was impaired at inclusion, but improved over time. Patients, especially men, had more functional gastrointestinal symptoms than controls. Conclusions: This study indicates that a minority of patients with PL has LPR and is cured by acid-reducing therapy. Disturbed plasma motilin levels and presence of functional gastrointestinal symptoms are found in PL. The impaired HRQOL improves over time.
  •  
47.
  • Persson, G. Rutger, et al. (författare)
  • Chronic periodontitis, a significant relationship with acute myocardial infarction.
  • 2003
  • Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:23, s. 2108-15
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic periodontitis (CP) has been associated with cardiovascular diseases. The study purposes were to identify the odds of acute myocardial infarction (AMI) and CP defined at different thresholds.METHODS AND RESULTS: We studied 80 subjects with clinically confirmed AMI and 80 matched control subjects with no evidence of cardiovascular disease all receiving a comprehensive periodontal examination. Statistical analysis demonstrated a difference in the proportion of sites with a periodontal probing depth >/=6.0mm (2.7% for non-AMI and 12.1% for AMI group, 95% CI: -2.8 to 0.01, P<0.05) but no difference in the extent of gingival bleeding was found between groups. The odds ratio of having AMI and periodontitis varied between 9.2:1 to 14.1:1 with the greatest odds ratio if bone loss exceeded 4mm at >/=50% of the teeth (OR: 14.1:1, 95% CI: 5.5 to 28.2, P<0.0001). The odds ratio remained significant also when only non-smokers were considered (51 subjects) (OR: 7.0:1, 95% CI: 2.0 to 24.3, P<0.01).CONCLUSIONS: Our findings suggest that patients who at routine dental visits demonstrate evidence of bone loss around several teeth can predictably be identified as being at risk for future AMI. Such subjects should be referred for medical and periodontal examinations and treatments.
  •  
48.
  • Persson, G. Rutger, et al. (författare)
  • Chronic periodontitis, a significant relationship with acute myocardial infarction.
  • 2003
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 24:23, s. 2108-15
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic periodontitis (CP) has been associated with cardiovascular diseases. The study purposes were to identify the odds of acute myocardial infarction (AMI) and CP defined at different thresholds. METHODS AND RESULTS: We studied 80 subjects with clinically confirmed AMI and 80 matched control subjects with no evidence of cardiovascular disease all receiving a comprehensive periodontal examination. Statistical analysis demonstrated a difference in the proportion of sites with a periodontal probing depth >/=6.0mm (2.7% for non-AMI and 12.1% for AMI group, 95% CI: -2.8 to 0.01, P<0.05) but no difference in the extent of gingival bleeding was found between groups. The odds ratio of having AMI and periodontitis varied between 9.2:1 to 14.1:1 with the greatest odds ratio if bone loss exceeded 4mm at >/=50% of the teeth (OR: 14.1:1, 95% CI: 5.5 to 28.2, P<0.0001). The odds ratio remained significant also when only non-smokers were considered (51 subjects) (OR: 7.0:1, 95% CI: 2.0 to 24.3, P<0.01). CONCLUSIONS: Our findings suggest that patients who at routine dental visits demonstrate evidence of bone loss around several teeth can predictably be identified as being at risk for future AMI. Such subjects should be referred for medical and periodontal examinations and treatments.
  •  
49.
  • Persson, G. Rutger, et al. (författare)
  • High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.
  • 2005
  • Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 32:3, s. 219-224
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels.OBJECTIVES: To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63).METHODS: hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied.RESULTS: Subjects with AMI had higher hsC-rp levels than control subjects (p<0.001, Mann-Whitney U-test). The odds that subjects in the control group with periodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, p<0.05). Stepwise linear regression analysis failed to include periodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, p<0.001). Serum WBC counts were significantly higher in control subjects with periodontitis (p<0.03) but not in subjects in the AMI group (p<0.57).CONCLUSIONS: (1) As expected, elevated serum hsC-rp concentration and serum WBC counts are associated with acute coronary heart disease. (2) Elevated serum hsC-rp values are associated with radiographically defined periodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model.
  •  
50.
  • Persson, G. Rutger, et al. (författare)
  • High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.
  • 2005
  • Ingår i: Journal of Clinical Periodontology. - : Blackwell Munksgaard. - 0303-6979 .- 1600-051X. ; 32:3, s. 219-224
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels. OBJECTIVES: To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63). METHODS: hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied. RESULTS: Subjects with AMI had higher hsC-rp levels than control subjects (p<0.001, Mann-Whitney U-test). The odds that subjects in the control group with periodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, p<0.05). Stepwise linear regression analysis failed to include periodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, p<0.001). Serum WBC counts were significantly higher in control subjects with periodontitis (p<0.03) but not in subjects in the AMI group (p<0.57). CONCLUSIONS: (1) As expected, elevated serum hsC-rp concentration and serum WBC counts are associated with acute coronary heart disease. (2) Elevated serum hsC-rp values are associated with radiographically defined periodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model.
  •  
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