1. |
- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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2. |
- Hillerdal, Gunnar, et al.
(author)
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Treatment of Malignant Pleural Mesothelioma with Carboplatin, Liposomized Doxorubicin, and Gemcitabine A Phase II Study
- 2008
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In: JOURNAL OF THORACIC ONCOLOGY. - 1556-0864. ; 3:11, s. 1325-1331
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Journal article (peer-reviewed)abstract
- Background: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination or liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.Methods: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-Lip, but all the others were followed for at least 4 years or until death.Results: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median Survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.Conclusion: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long Survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" Surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.
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3. |
- Sundstrom, Anders, et al.
(author)
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Increased risk of abdominal wall hernia associated with combination anti-retroviral therapy in HIV-infected patients-results from a Swedish cohort-study
- 2010
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 19:5, s. 465-473
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Journal article (peer-reviewed)abstract
- Purpose To determine if anti-retroviral therapy (ART) in HIV-infected patients is associated with an increased risk for development of abdominal wall hernia. Methods A cohort study of 1072 HIV-infected patients in Sweden. Information was collected by questionnaires to patients and treating physicians, chart reviews by study physicians and regular blood tests for metabolic disorders. Adjusted relative risks were estimated by Cox proportional hazards models. Results Sixty-three patients (5.9%) developed abdominal wall hernia during the study period, 34 inguinal and 29 midline. Compared to the male general population, inguinal hernia was twice as common in the male study population, standardized incidence ratio (SIR) 2.0 (95% confidence interval (CI) 1.4-2.8). An increased incidence rate of abdominal wall hernia was found in patients exposed to ART, 11.3 per 1000 person-years (PY) compared with therapy naives, 2.1 per 1000 PY. When adjusting for confounding risk-factors, ART containing protease inhibitors (Pis) during the 2nd and 3rd year of treatment was associated with the development of midline hernia with a hazard ratio (HR) of 10.7 (95%CI 1.3-85.7), and of inguinal hernia with an HR of 4.4 (95%CI 1.1-16.6). Other independent risk factors were age and diabetes/impaired fasting glucose for midline hernia, and age and a previous diagnosis of AIDS for inguinal hernia. Conclusions We found an increased risk of developing abdominal wall hernia associated with PI-containing ART. The size of the study population did not permit any conclusions regarding non-PI-containing ART. Copyright (C) 2010 John Wiley & Sons, Ltd.
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4. |
- Söderberg, Stefan, et al.
(author)
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MEASURES OF WAIST AND HIP MODIFY SEX-SPECIFIC ASSOCIATIONS BETWEEN BODY MASS INDEX AND PREVALENCE OF CORONARY ARTERY CALCIFICATION IN OPPOSITE DIRECTIONS
- 2019
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In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 13-13
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Journal article (other academic/artistic)abstract
- Background: Obesity is associated with increased risk of cardiovascular disease. However, there is still a debate whether accumulation of fat in certain depots modifies this risk. Using data from the CArdioPulmonary bioImage Study (SCAPIS), we investigated if anthropometric measurements of obesity (waist and hip) modifies the risk of coronary artery calcification. Methods: In the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on coronary artery calcification score (CACS) and anthropometry were recorded and traditional cardiovascular risk factors were measured. Body mass index (BMI) was categorized as; <25, 25-30, 30-35 and >35 kg/m2 , quartiles of waist and hip circumferences were constructed within each BMI category and compared using the lowest quartile as reference. Results were adjusted for site, age, smoking and diabetes status. Results: Obesity (BMI >30 kg/m2 ) was found in 21.9% of men and in 20.5% of women. In both sexes the odds ratio (OR) for CACS >0 increased with increasing BMI categories: comparing <25 and >35 kg/m2 , OR = 2.1 (95% CI: 1.6-2.7) for men and OR = 1.4 (1.2-1.8) for women. In addition, increasing quartiles of waist significantly increased the prevalence of CACS >0 for men [p = 0.05; OR = 1.2 (1.0-1.4) for highest quartile] and women [p = 0.005; OR = 1.3 (1.1-1.5)] while increasing quartiles of hip significantly decreased the prevalence for men [p = 0.005; OR = 0.8 (0.6-0.9)] and women [p = 0.04; OR = 0.8 (0.7-0.9)]. Data on education level and physical activity did not affect the model. Conclusion: Increased BMI is associated with increased prevalence of coronary artery calcification and the distribution of fat modifies this risk. Our results suggest that gluteofemoral adipose tissue (hip) counteracts the negative effects associated with BMI and abdominal adipose tissue (waist).
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5. |
- Bahmanyar, Shahram, et al.
(author)
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Pharmacological treatment and demographic characteristics of pediatric patients with Attention Deficit Hyperactivity Disorder, Sweden
- 2013
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 23:12, s. 1732-1738
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Journal article (peer-reviewed)abstract
- The aim of this study was to describe the pediatric population with ADHD and their pharmacological treatment. Using the Swedish National Patient Register and the Prescribed Drug Register we identified individuals below 19 years of age who were diagnosed or medically treated for ADHD for the first time 2006-2007. The unique patient identifiers were used to link information from the two registers to describe demographic characteristics, hospital care and drug treatments. Logistic regression model estimated the association between age, sex, frequency of hospitalization, diagnosis or treatment for other mental disorders and risk of gap in the treatment. Totally the study included 7931 patients of whom 74% were males. The mean age at first diagnosis was 12 years. Some 84% were medically treated for ADHD and approximately 90% received methylphenidate as the first substance. Combination therapy was rare and the most common combination was methylphenidate and atomoxetine. More than 55% of the patients, which could be followed up for two years after start of treatment, had at least one treatment gap of six months. Older age at diagnosis, lower number of hospitalizations and comorbidity with other mental disorders increased risks of gaps in medication. Approximately one fifth of the patients recorded in the National Patient Register as diagnosed with ADHD did not receive pharmacological treatment. Medication adherence seems to be low, when measured as gaps in treatment.
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6. |
- Bergendal, Annica, et al.
(author)
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Non-steroidal anti-inflammatory drugs and venous thromboembolism in women
- 2013
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 22:6, s. 658-666
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Journal article (peer-reviewed)abstract
- Background Non-steroidal anti-inflammatory drugs (NSAIDs) might increase the risk of venous thromboembolism (VTE), and risks might differ by type of NSAID. Compared with men, women have a higher incidence of VTE at younger age, and they more often use NSAIDs. Objectives To assess risks of VTE in young and middle-aged women in association with use of NSAIDs. Patients/Methods In a nationwide case-control study (Thrombo Embolism Hormone Study) performed in Sweden 2003-2009, we included as cases 1433 women, 18 to 64years of age with a first time VTE. Controls were 1402 randomly selected women, frequency matched by age. Information was obtained by telephone interviews and DNA analyses of blood samples. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for degree of immobilization, chronic disease, smoking, body mass index, use of hormonal contraception, hormone therapy or other NSAIDs. Results Use of NSAIDs was not associated with increased risks of VTE (OR=0.98, 95% CI 0.80-1.19). The OR was 0.88 for propionic acid derivatives (95% CI 0.72-1.10), 1.18 for acetic acid derivatives (95% CI 0.82-1.70) and 1.76 for coxibs (95% CI 0.73-4.27). For users of acetic acid derivatives and coxibs, the ORs increased by cumulative dose. Carriership of the prothrombin gene mutation or factor V Leiden had only minor effects on the results. Conclusions We found no increased risks of VTE in association with use of NSAIDs. Users of high cumulative doses of acetic acid derivatives and coxibs had the highest risks, suggesting a relationship with cyclooxygenase selectivity and dose.
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7. |
- Bergendal, Annica, et al.
(author)
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Risk factors for venous thromboembolism in pre- and postmenopausal women
- 2012
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In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:4, s. 596-601
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Journal article (peer-reviewed)abstract
- IntroductionHemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women.MethodIn a nationwide case–control study we included as cases 1470 women, 18 to 64 years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThe ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status.ConclusionMenopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.
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8. |
- Bjornsdottir, Sigridur, et al.
(author)
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Drug Prescription Patterns in Patients With Addison's Disease : A Swedish Population-Based Cohort Study
- 2013
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:5, s. 2009-2018
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Journal article (peer-reviewed)abstract
- Context: There are no published data on drug prescription in patients with Addison's disease ( AD). Objective: Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. Design and Setting: We conducted a population-based cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. Main Outcome Measure: We determined the ratio of observed to expected number of patients treated with prescribed drugs. Results: Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Conclusion: Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.
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9. |
- Björkman, Per, et al.
(author)
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Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels
- 1998
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In: Transfusion. - 1537-2995. ; 38:4, s. 378-384
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Journal article (peer-reviewed)abstract
- BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti-HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.
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