| 1. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 2. |
- Stitziel, Nathan O., et al.
(författare)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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| 3. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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| 5. |
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| 6. |
- Assey, Vincent D., et al.
(författare)
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Improved salt iodation methods for small-scale salt producers in low-resource settings in Tanzania
- 2009
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 9, s. 187-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Universal salt iodation will prevent iodine deficiency disorders (IDD). Globally, salt-iodation technologies mostly target large and medium-scale salt-producers. Since most producers in low-income countries are small-scale, we examined and improved the performance of hand and knapsack-sprayers used locally in Tanzania. METHODS: We studied three salt facilities on the Bagamoyo coast, investigating procedures for preparing potassium-iodate solution, salt spraying and mixing. Different concentrations of solution were prepared and tested using different iodation methods, with the aim of attaining correct and homogeneous iodine levels under real-life conditions. Levels achieved by manual mixing were compared to those achieved by machine mixing. RESULTS: The overall median iodation level in samples of salt iodated using previously existing methods was 10.6 ppm (range 1.1 - 110.0 ppm), with much higher levels in the top than the bottom layers of the salt bags, p < 0.0001. Experimentation using knapsack-sprayers and manual mixing led to the reliable achievement of levels (60.9 ppm +/- 7.4) that fell within the recommended range of 40 - 80 ppm. The improved methods yielded homogenous iodine concentrations in all layers of salt-bags (p = 0.58) with 96% of the samples (n = 45) falling within 40 - 80 ppm compared to only 9% (n = 45) before the experiment and training (p < 0.0001). For knapsack-spraying, a machine mixer improved the iodine levels and homogeneity slightly compared to manual mixing (p = 0.05). CONCLUSION: Supervised, standardized salt iodation procedures adapted to local circumstances can yield homogeneous iodine levels within the required range, overcoming a major obstacle to universal salt iodation.
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| 7. |
- Aubert, Salome, et al.
(författare)
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Global Matrix 3.0 Physical Activity Report Card Grades for Children and Youth: Results and Analysis From 49 Countries
- 2018
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Ingår i: Journal of Physical Activity and Health. - : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 15, s. S251-S273
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulating sufficient moderate to vigorous physical activity is recognized as a key determinant of physical, physiological, developmental, mental, cognitive, and social health among children and youth (aged 5-17 y). The Global Matrix 3.0 of Report Card grades on physical activity was developed to achieve a better understanding of the global variation in child and youth physical activity and associated supports. Methods: Work groups from 49 countries followed harmonized procedures to develop their Report Cards by grading 10 common indicators using the best available data. The participating countries were divided into 3 categories using the United Nations human development index (HDI) classification (low or medium, high, and very high HDI). Results: A total of 490 grades, including 369 letter grades and 121 incomplete grades, were assigned by the 49 work groups. Overall, an average grade of "C-," "D+," and "C-" was obtained for the low and medium HDI countries, high HDI countries, and very high HDI countries, respectively. Conclusions: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide. Strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
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| 8. |
- Aubert, Salome, et al.
(författare)
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Report Card Grades on the Physical Activity of Children and Youth Comparing 30 Very High Human Development Index Countries
- 2018
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Ingår i: Journal of Physical Activity and Health. - : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 15, s. S298-S314
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Tidskriftsartikel (refereegranskat)abstract
- Background: To better understand the childhood physical inactivity crisis, Report Cards on physical activity of children and youth were prepared concurrently in 30 very high Human Development Index countries. The aim of this article was to present, describe, and compare the findings from these Report Cards. Methods: The Report Cards were developed using a harmonized process for data gathering, assessing, and assigning grades to 10 common physical activity indicators. Descriptive statistics were calculated after converting letter grades to interval variables, and correlational analyses between the 10 common indicators were performed using Spearmans rank correlation coefficients. Results: A matrix of 300 grades was obtained with substantial variations within and between countries. Low grades were observed for behavioral indicators, and higher grades were observed for sources of influence indicators, indicating a disconnect between supports and desired behaviors. Conclusion: This analysis summarizes the level and context of the physical activity of children and youth among very high Human Development Index countries, and provides additional evidence that the situation regarding physical activity in children and youth is very concerning. Unless a major shift to a more active lifestyle happens soon, a high rate of noncommunicable diseases can be anticipated when this generation of children reaches adulthood.
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| 9. |
- Dawson, Ian, et al.
(författare)
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Diffracting Digital Images in the Making
- 2021
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Ingår i: Visual Resources. - : Taylor & Francis. - 0197-3762 .- 1477-2809. ; 37:1, s. 31-43
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a diffractive dialogue between ethnographic accounts of imagery, digital or computational imaging, and art and archaeology practices. It develops the notion of images in the making in the context of the digital domain, to discuss what an image is and can be today. It focusses on two digital imaging techniques developed within archaeology and cultural heritage – Reflectance Transformation Imaging (RTI) and Structure from Motion photogrammetry (SfM) – exploring how these techniques play out in heritage and art world contexts and practices. The paper highlights digital images as unstable compositions, and explores how digital images in the making enable us to reconsider the shifting temporal character of the image, and discuss the way in which the digital image forces us to disrupt the representational assumptions bound up in the relationship between the virtual and the actual. The authors argue that the diffractive moments in these encounters between archaeology and art practice disclose the potential of digital imaging to recursively question the complex ontological composition of images and the ability of images to act and affect.
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| 10. |
- Dellenmark-Blom, Michaela, et al.
(författare)
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Prevalence of Mental Health Problems, Associated Factors, and Health-Related Quality of Life in Children with Long-Gap Esophageal Atresia in Sweden
- 2023
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Ingår i: Journal of Pediatric Surgery. - : Elsevier. - 0022-3468 .- 1531-5037. ; 58:9, s. 1646-1655
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with long-gap esophageal atresia (LGEA) face a high risk of digestive and respiratory morbidity, but their mental health outcomes have not been investigated. We aimed to identify the prevalence of mental health problems in children with LGEA, associated factors and health-related quality of life (HRQOL).Methods: Twenty-six children with LGEA aged 3-17 were recruited nationwide in Sweden. One of their parents and adolescents aged 11-17 completed information on the child's mental health (Strength and Difficulties Questionnaire), generic (PedsQL 4.0) and condition-specific HRQOL (EA-QOL). Parents gave information on current child symptomatology. Mental health level was determined using validated norms; abnormal >= 90 percentile/borderline >= 80 percentile/normal. Elevated levels were considered borderline/abnormal. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05.Results: Twelve children with LGEA aged 3-17 (46%) had elevated scores of >= 1 mental health domain in parent-reports, whereas 2 adolescents (15%) in self-reports. In parent-reports, 31% of the children had elevated levels of peer relationship problems, with associated factors being child sex male (p = 0.037), airway infections (p = 0.002) and disturbed night sleep (p = 0.025). Similarly, 31% showed elevated levels of hyperactivity/inattention, and associated factors were male sex (p = 0.005), asthma (p = 0.028) and disturbed night sleep (p = 0.036). Elevated levels of emotional symptoms, seen in 20%, were related to swallowing difficulties (p = 0.038) and vomiting problems (p = 0.045). Mental health problems correlated negatively with many HRQOL domains (p < 0.05).Conclusions: Children with LGEA risk mental health difficulties according to parent-reports, especially peer relationship problems and hyperactivity/inattention, with main risk factors being male sex, airway problems and sleep disturbances. This should be considered in follow-up care and research, particularly since their mental health problems may impair HRQOL.
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| 11. |
- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
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Schooling experiences in children with long-gap esophageal atresia compared with children with esophageal atresia and primary anastomosis: a Swedish study
- 2023
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Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children's development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden in comparison with children with EA who had primary anastomosis.MethodChildren with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child's school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared between 26 children with LGEA to that from 95 children with EA who had PA, a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal & GE; 90 percentile. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05.ResultsFormal school-based support was reported in 17 (65.4%) children with LGEA and concerned support with nutritional intake (60%), education (50%) and medical/special health needs (35%). The prevalence of school-based support was significantly higher compared to children with PA overall (36.8%, p = 0.013) and regarding nutritional intake support (20%, p < 0.001). In children with LGEA, school-based support was related to low birth weight (p = 0.036), young child age (p = 0.014), height & LE; -2SD for age/sex (p = 0.024) and an increased number of aerodigestive symptoms (p < 0.05). All children with LGEA who had abnormal mental health scores had school-based support, except for one child. Nine children with LGEA (36%) had school absence & GE; 1times/month the past year, more frequently because of colds/airway infections (p = 0.045) and GI-specific problems compared to PA (p = 0.003). School functioning scores were not significantly different from children with PA (p = 0.34) but correlated negatively with school-based support (< 0.001) and school absence (p = 0.002). One parent out of 26 reported their child's school satisfaction as "not good".ConclusionsChildren with LGEA commonly receive school-based support, reflecting multifaceted daily needs and disease severity. School absence is frequent and related to poorer school functioning. Future research focusing on academic achievement in children with EA is needed.
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| 12. |
- Edgren, Gustaf, et al.
(författare)
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Improving health profile of blood donors as a consequence of transfusion safety efforts
- 2007
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 47:11, s. 2017-2024
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transfusion safety rests heavily on the health of blood donors. Although they are perceived as being healthier than average, little is known about their long-term disease patterns and to which extent the blood banks' continuous efforts to optimize donor selection has resulted in improvements. Mortality and cancer incidence among blood donors in Sweden and Denmark was investigated. Study Design and Methods: All computerized blood bank databases were compiled into one database, which was linked to national population and health data registers. With a retrospective cohort study design, 1,110,329 blood donors were followed for up to 35 years from first computer-registered blood donation to death, emigration, or December 31, 2002. Standardized mortality and incidence ratios expressed relative risk of death and cancer comparing blood donors to the general population. Results: Blood donors had an overall mortality 30 percent lower (99% confidence interval [CI] 29%-31%) and cancer incidence 4 percent lower (99% CI 2%-5%) than the background population. Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation. Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier. Conclusion: Blood donors enjoy better than average health. Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the selection of a particularly healthy subpopulation.
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| 13. |
- Engelen, Marscha M., et al.
(författare)
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The Association Between Stuttering Burden and Psychosocial Aspects of Life in Adults
- 2024
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Ingår i: Journal of Speech, Language and Hearing Research. - 1092-4388 .- 1558-9102. ; 67:5, s. 1385-1399
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life.METHOD: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden.RESULTS: We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden.CONCLUSIONS: Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering.SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25582980.
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| 14. |
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| 15. |
- Ganna, Andrea, et al.
(författare)
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Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction
- 2013
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 33:9, s. 2267-2272
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Tidskriftsartikel (refereegranskat)abstract
- Objective-Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. Approach and Results-We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P<0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Conclusions-Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.
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| 16. |
- Ganna, Andrea, 1985-, et al.
(författare)
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Risk prediction measures for case-cohort and nested case-control designs : an application to cardiovascular disease.
- 2012
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:7, s. 715-724
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Tidskriftsartikel (refereegranskat)abstract
- Case-cohort and nested case-control designs are often used to select an appropriate subsample of individuals from prospective cohort studies. Despite the great attention that has been given to the calculation of association estimators, no formal methods have been described for estimating risk prediction measures from these 2 sampling designs. Using real data from the Swedish Twin Registry (2004-2009), the authors sampled unstratified and stratified (matched) case-cohort and nested case-control subsamples and compared them with the full cohort (as "gold standard"). The real biomarker (high density lipoprotein cholesterol) and simulated biomarkers (BIO1 and BIO2) were studied in terms of association with cardiovascular disease, individual risk of cardiovascular disease at 3 years, and main prediction metrics. Overall, stratification improved efficiency, with stratified case-cohort designs being comparable to matched nested case-control designs. Individual risks and prediction measures calculated by using case-cohort and nested case-control designs after appropriate reweighting could be assessed with good efficiency, except for the finely matched nested case-control design, where matching variables could not be included in the individual risk estimation. In conclusion, the authors have shown that case-cohort and nested case-control designs can be used in settings where the research aim is to evaluate the prediction ability of new markers and that matching strategies for nested case-control designs may lead to biased prediction measures.
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| 17. |
- Grünewald, Maria, 1976-
(författare)
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Design and analysis of response selective samples in observational studies
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Outcome dependent sampling may increase efficiency in observational studies. It is however not always obvious how to sample efficiently, and how to analyze the resulting data without introducing bias. This thesis describes a general framework for efficiency calculations in multistage sampling, with focus on what is sometimes referred to as ascertainment sampling. A method for correcting for the sampling scheme in analysis of ascertainment samples is also presented. Simulation based methods are used to overcome computational issues in both efficiency calculations and analysis of data.
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| 18. |
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| 19. |
- Henriksson, Hanna, 1977-
(författare)
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Development of body composition and its relationship with physical activity in healthy Swedish children : A longitudinal study until 4.5 years of age including evaluation of methods to assess physical activity and energy intake
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Childhood obesity according to the World Health Organization is one of the most serious public health challenges of the 21st century. The proportion of childhood obesity is high both globally and in Sweden. This is of great concern since obese children tend to stay obese in adulthood. In order to develop strategies to prevent early childhood obesity more knowledge is needed regarding factors explaining why children become overweight and obese. Preventive strategies require accurate and easy-to-use methods to assess physical activity in response to energy expenditure as well as energy intake in young children, but such methods are largely lacking or have shown limited accuracy. The aims of this thesis were: 1) to describe the longitudinal development of body composition from 1 week to 4.5 years of age; 2) to study relationships between measures of body composition and the physical activity level (PAL) at 1.5 and 3 years of age; 3) to evaluate if heart rate recording and movement registration using Actiheart can capture variations in total energy expenditure (TEE) and activity energy expenditure (AEE) at 1.5 and 3 years; 4) to evaluate the potential of a 7-day activity diary to assess PAL at 1.5 and 3 years of age; 5) to evaluate a new tool (TECH) using mobile phones for assessing energy intake at 3 years of age.Healthy children were investigated at 1 and 12 weeks (n=44), at 1.5 (n=44), 3 (n=33) and 4.5 (n=26) years of age. Body composition was measured using air-displacement plethysmography at 1 and 12 weeks and at 4.5 years of age. At 1.5 and 3 years, body composition, TEE, PAL and AEE were assessed using the doubly labelled water method and indirect calorimetry. Heart rate and movements were recorded using Actiheart (four days) and physical activities were registered using the 7-day diary. Energy intake was assessed using TECH during one complete 24-hour period.Average percentage of total body fat (TBF) and average fat mass index (FMI) were higher (+3 to +81 %), while fat-free mass index (FFMI) was slightly lower (-2 to -9 %), in children in the study from 12 weeks until 4.5 years of age when compared to corresponding reference values. A relationship between TBF% and PAL was found both at 1.5 and 3 years of age. At 3 years, but not at 1.5 years, this could be explained by a relationship between PAL and FFMI. Actiheart recordings explained a significant but small fraction (8%) of the variation in free-living TEE at 1.5 and 3 years, and in AEE (6 %) at 3 years, above that explained by body composition variables. At 1.5 and 3 years of age, PAL estimated by means of the activity diary using metabolic equivalent (MET) values by Ainsworth et al. was not significantly different from reference PAL, but the accuracy for individuals was low. Average energy intake assessed by TECH was not significantly different from TEE. However, the accuracy for individuals was poor.The results of this thesis suggest that 1) The higher body fatness of the children in the study compared to the corresponding reference values may indicate the presence of a secular trend in body composition development characterized by a high body fatness. 2) Body fatness might counteract physical activity at 1.5 years of age when the capacity to perform physical activity is limited, but not at 3 years of age when such a capacity has been developed. 3) Actiheart recordings explained a significant but small fraction of the variation in TEE at 1.5 and 3 years, and in AEE at 3 years of age, above that explained by body composition variables. 4) The activity diary and TECH produced mean values in agreement with reference PAL and TEE, respectively, but the accuracy for individual children was low.In conclusion, the results of this thesis suggest the presence of a secular trend in body composition development in healthy Swedish children, from infancy up to 4.5 years of age, which is characterized by a high body fatness. Methods to assess physical activity and energy intake at 1.5 and 3 years of age provided some promising results on a group level, although further research is needed to increase the accuracy of these methods in individual children.
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| 20. |
- Kamper-Jörgensen, Mads, et al.
(författare)
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Survival after blood transfusion
- 2008
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 48:12, s. 2577-2584
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Tidskriftsartikel (refereegranskat)abstract
- Long-term survival of transfusion recipients has rarely been studied. This study examines short- and long-term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population. Population-based cohort study of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first registered transfusion. Three months after the first transfusion, 84.3 percent of recipients were alive. One-, 5-, and 20-year posttransfusion survival was 73.7, 53.4, and 27.0 percent, respectively. Survival was slightly poorer in men than in women, decreased with increasing age, and was worst for recipients transfused at departments of internal medicine. The first 3 months after the first transfusion, the standardized mortality ratio (SMR) was 17.6 times higher in transfusion recipients than in the general population. One to 4 years after first transfusion, the SMR was 2.1 and even after 17 years the SMR remained significantly 1.3-fold increased. The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease as well as for cost-benefit estimation of new blood safety interventions.
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| 21. |
- Kariippanon, Katharina E., et al.
(författare)
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Levels and Correlates of Objectively Measured Sedentary Behavior in Young Children : SUNRISE Study Results from 19 Countries
- 2022
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Ingår i: Medicine & Science in Sports & Exercise. - : Lippincott, Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 54:7, s. 1123-1130
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Tidskriftsartikel (refereegranskat)abstract
- Purpose There is a paucity of global data on sedentary behavior during early childhood. The purpose of this study was to examine how device-measured sedentary behavior in young children differed across geographically, economically, and sociodemographically diverse populations, in an international sample. Methods This multinational, cross-sectional study included data from 1071 children 3-5 yr old from 19 countries, collected between 2018 and 2020 (pre-COVID). Sedentary behavior was measured for three consecutive days using activPAL accelerometers. Sedentary time, sedentary fragmentation, and seated transport duration were calculated. Linear mixed models were used to examine the differences in sedentary behavior variables between sex, country-level income groups, urban/rural settings, and population density. Results Children spent 56% (7.4 h) of their waking time sedentary. The longest average bout duration was 81.1 +/- 45.4 min, and an average of 61.1 +/- 50.1 min center dot d(-1) was spent in seated transport. Children from upper-middle-income and high-income countries spent a greater proportion of the day sedentary, accrued more sedentary bouts, had shorter breaks between sedentary bouts, and spent significantly more time in seated transport, compared with children from low-income and lower-middle-income countries. Sex and urban/rural residential setting were not associated with any outcomes. Higher population density was associated with several higher sedentary behavior measures. Conclusions These data advance our understanding of young childrens sedentary behavior patterns globally. Country income levels and population density appear to be stronger drivers of the observed differences, than sex or rural/urban residential setting.
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| 22. |
- Lee, Myeongjee, et al.
(författare)
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Differences in survival for patients with familial and sporadic cancer
- 2016
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Family history of cancer is a well-known risk factor but the role of family history in survival is less clear. The aim of this study was to investigate the association between family history and cancer survival for the common cancers in Sweden. Using the Swedish population-based registers, patients diagnosed with the most common cancers were followed for cancer-specific death during 1991-2010. We used multivariate proportional hazards (Cox) regression models to contrast the survival of patients with a family history of cancer (individuals whose parent or sibling had a concordant cancer) to the survival of patients without a family history. Family history of cancer had a modest protective effect on survival for breast cancer (hazard ratio (HR) = 0.88, 95% confidence interval (95% CI) = 0.81 to 0.96) and prostate cancer (HR = 0.82, 95% CI = 0.75 to 0.90). In contrast, family history of cancer was associated with worse survival for nervous system cancers (HR = 1.24, 95% CI = 1.05 to 1.47) and ovarian cancer (HR = 1.20, 95% CI = 1.01 to 1.43). Furthermore, the poorer survival for ovarian cancer was consistent with a higher FIGO stage and a greater proportion of more aggressive tumors of the serous type. The better survival for patients with a family history of breast and prostate cancer may be due to medical surveillance of family members. The poor survival for ovarian cancer patients with an affected mother or sister is multifactorial, suggesting that these cancers are more aggressive than their sporadic counterparts.
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| 23. |
- Leu, Monica, 1977, et al.
(författare)
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Bias and bias-correction of estimates of familial risk in population-based register
- 2009
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Ingår i: International Journal of Epidemiology. - 0300-5771. ; 39:1, s. 80-8
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Tidskriftsartikel (refereegranskat)abstract
- Background In addition to guiding molecular epidemiology investigations, estimates of the increased risk of disease in relatives of affected persons are also important for screening and counselling decisions. Since precise estimation of such familial risks (FRs) requires large sample sizes, many of the estimates in common use have been obtained from historical electronic records of disease in entire populations, where the relatives of affected and unaffected persons are compared. These estimates may be biased due to failure to identify relatives as affected if they are diagnosed before the start-up date of disease registration. Methods This article presents a method for correcting the bias in FR estimates from such misclassification of family history, using a simple formula that depends on the prevalence and sensitivity of the observed family history. The sensitivity is estimated by using the R package poplab to create realistic populations of related individuals and then imposing the start-up effect of disease registration. Results For a range of FRs, the truncation of family history is demonstrated to result in non-differential misclassification, and sensitivity that has little or no dependence on the FR. The bias is most pronounced for high FRs and for registers with a short life span, and increases with the age of the study cohort. In all the situations studied, the bias-corrected estimates are in excellent agreement with the true values. Conclusions In summary, our method can correct the inevitable bias in FRs induced by using electronic population data, and is a feasible alternative to the use of validation samples.
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| 24. |
- Leu, Monica, 1977, et al.
(författare)
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Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers
- 2008
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 100:18, s. 1318-25
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Tidskriftsartikel (refereegranskat)abstract
- Background Bias in estimates of familial cancer may result if population-based registers fail to identify relatives as affected when disease occurs before the start-up of registration (ie, “left-truncation” of family history). Methods Apparent familial relative risks (among offspring of parents with cancer) of colorectal, lung, breast, and prostate cancers and melanoma in a Swedish cohort were compared with relative risks in a simulated population. The study cohort (approximately 7 million individuals) was based on the Swedish MultiGenerational Register linked to the Swedish Cancer Register for the period 1961–2002. A similar population of related individuals (approximately 7 million) with complete family information was simulated by using the R-package PopLab and used to estimate the sensitivity of the observed family history. This sensitivity was then used to calculate corrected age group–specific and overall risks, which were compared with the apparent familial risks of cancer in the cohort. Result The apparent familial risks for colorectal, lung, breast, and prostate cancers and melanoma were 1.99 (95% confidence interval [CI]=1.85 to 2.14), 2.05 (95% CI=1.86 to 2.26), 1.84 (95% CI=1.76 to 1.92), 2.33 (95% CI=2.19 to 2.48), and 2.68 (95% CI=2.35 to 3.07), with corresponding absolute rates of 3.69, 2.59, 16.05, 10.38, and 2.96 per 10000 person-years, among offspring of parents diagnosed with the same cancer. Corrected age group–specific and overall estimates of the familial risks were close to these apparent risks for all studied cancers (all approximately 2.0), except for melanoma. For melanoma, the corrected estimate of 3.18 (95% CI=2.73 to 3.64) was somewhat larger than the apparent estimate and was not included in the confidence interval for the apparent estimate. When the exposure of interest was a parent affected at a younger age, this bias was more pronounced; the apparent estimate for melanoma changed from 4.07 (95% CI=3.21 to 5.16) to 5.67 (95% CI=4.51 to 6.83) after correction. Conclusions For common cancers, risk estimates from the Swedish MultiGenerational cohort do not generally appear to be biased by left-truncation.
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| 25. |
- Leu, Monica, 1977, et al.
(författare)
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“Population Lab”: The creation of virtual populations in Genetic Epidemiology Research
- 2007
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Ingår i: Epidemiology. - 1044-3983. ; 18:4, s. 433-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies of familial aggregation of disease routinely use linked population registers to construct retrospective cohorts. Although such resources have provided numerous estimates of familial risk, little is known regarding the sensitivity of the estimates to assumed disease models, changing demographics and incidence, and incompleteness of the data. Furthermore, there are no standard tools for testing the validity of estimates from standard epidemiologic designs and from new analytic strategies using register data. METHODS: We present a method and a software package for simulating realistic populations of related individuals, using easily available vital statistics (population counts and fertility and mortality rates). The virtual population is stored in a pedigree file, allowing for easy retrieval of relatives and family structures. We simulate breast cancer in our population using age-specific incidence rates. RESULTS: The Swedish population is simulated as dynamically evolving over the calendar period 1955-2002. The simulated and real population agree well on important features such as age profile, sibship size distribution, and average age at first birth. Using breast cancer as an example, we present several models of familial disease aggregation and show that the parameters used in the simulations are faithfully estimated. In addition, we illustrate how our simulated population provides insight into how incomplete family history in real register data can affect estimates of familial risk. CONCLUSIONS: This simulation method can be used to investigate various underlying models of disease aggregation in families and enhance the development of optimal approaches for family studies. The software package, Population Lab, is available for free download (http://www.meb.ki.se/ approximately marrei/software/poplab/ and http://cran.at.r-project.org/).
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| 26. |
- Leu, Monica, 1977, et al.
(författare)
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The impact of truncation and missing family links in population-based registers on familial risk estimates
- 2007
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Ingår i: American Journal of Epidemiology. - 0002-9262 .- 1476-6256. ; 166:12, s. 1461-7
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Tidskriftsartikel (refereegranskat)abstract
- Family history information is often incomplete in population-based disease registers because of truncation and/or missing family links. In this study, the authors simulated complete populations of related individuals with realistic age, family structure, and incidence rates. After mimicking the realities of register-based data, such as left truncation of family history and missing family links due to death, the authors explored recovery of familial association parameters from standard epidemiologic models. Truncation of family history produced almost no bias for a familial risk of 2 and 50 years of follow-up, but it had a dramatic impact when the familial risk was 10. The age distribution of disease and the magnitude of background incidence rates also affected family history loss and thus the magnitude of bias. One can safeguard against bias by starting follow-up later, with the number of registration years to be ignored in the analysis depending on the value of familial risk. The missing familial links due to death had no effect, except when there was differential mortality for cases with and without a family history of disease. In summary, truncation, and to a lesser extent missing family links, induces bias in familial risk estimates from population-based registers.
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| 27. |
- Nahtman, Tatjana, 1972-, et al.
(författare)
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Validation of peptide epitope microarray experiments and extraction of quality data
- 2007
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Ingår i: Journal of Immunological Methods. - 0022-1759. ; 328:1-2
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Tidskriftsartikel (refereegranskat)abstract
- Abstract.Within the last decade, the development of antigen microarray slides has enabled the simultaneous measurement of serum reactivity to hundreds of peptides in a single biological sample. Despite this considerable scientific progress, many issues remain regarding the quality, analysis and interpretation of the data these slides produce. There is currently no accepted approach to guide data analysis, and researchers use a wide variety of statistical methods and software tools. We designed and implemented a laboratory experiment to assess the reliability and range of measurement of peptide microarray data, and present graphical and statistical procedures for pre-processing so that quality data can be extracted for addressing biological hypotheses.
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| 28. |
- Ndiaye, Aminata, et al.
(författare)
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Growth patterns and their contributing factors among HIV-exposed uninfected infants
- 2021
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Ingår i: Maternal and Child Nutrition. - : Wiley. - 1740-8695 .- 1740-8709. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- With expanded HIV treatment and prevention programmes, most infants born to HIV-positive women are uninfected, but the patterns and determinants of their growth are not well described. This study aimed to assess growth patterns in a cohort of HIV-exposed uninfected (HEU) infants who participated in an experimental HIV vaccine trial and to test for associations with maternal and infant factors, including in-utero exposure to antiretroviral therapy (ART), mode of delivery, exclusive breastfeeding, mother's education and receipt of the vaccine. Infants in the trial were seen at regular clinic visits from birth to 48 weeks of age. From the anthropometric measurements at these visits, weight-for-age z-scores (WAZ), weight-for-length z-scores (WLZ) and length-for-age z-scores (LAZ) were computed using World Health Organization (WHO) software and reference tables. Growth patterns were investigated with respect to maternal and infant factors, using linear mixed regression models. From 94 infants included at birth, growth data were available for 75.5% at 48 weeks. The determinants of infant growth in this population are multifactorial: infant LAZ during the first year was significantly lower among infants delivered by caesarean section (p = 0.043); both WAZ and LAZ were depressed among infants with longer exposure to maternal ART (WAZ: p = 0.015; LAZ: p < 0.0001) and among infants of mothers with lower educational level (WAZ: p = 0.038; LAZ: p < 0.0001); the effect of maternal education was modified by breastfeeding practice, with no differences seen in exclusively breastfed infants. These findings inform intervention strategies to preserve growth in this vulnerable infant population.
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| 29. |
- Ning, Yilin, et al.
(författare)
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Handling ties in continuous outcomes for confounder adjustment with rank-ordered logit and its application to ordinal outcomes
- 2020
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Ingår i: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 29:2, s. 437-454
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Tidskriftsartikel (refereegranskat)abstract
- The rank-ordered logit (rologit) model was recently introduced as a robust approach for analysing continuous outcomes, with the linear exposure effect estimated by scaling the rank-based log-odds estimate. Here we extend the application of the rologit model to continuous outcomes with ties and ordinal outcomes treated as imperfectly-observed continuous outcomes. By identifying the functional relationship between survival times and continuous outcomes, we explicitly establish the equivalence between the rologit and Cox models to justify the use of the Breslow, Efron and perturbation methods in the analysis of continuous outcomes with ties. Using simulation, we found all three methods perform well with few ties. Although an increasing extent of ties increased the bias of the log-odds and linear effect estimates and resulted in reduced power, which was somewhat worse when the model was mis-specified, the perturbation method maintained a type I error around 5%, while the Efron method became conservative with heavy ties but outperformed Breslow. In general, the perturbation method had the highest power, followed by the Efron and then the Breslow method. We applied our approach to three real-life datasets, demonstrating a seamless analytical workflow that uses stratification for confounder adjustment in studies of continuous and ordinal outcomes.
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| 30. |
- Norda, Rut, et al.
(författare)
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The impact of plasma preparations and their storage time on short-term posttransfusion mortality : A population-based study using the Scandinavian Donation and Transfusion database
- 2012
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Ingår i: Journal of Trauma and Acute Care Surgery. - 2163-0755 .- 2163-0763. ; 72:4, s. 954-961
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The treatment of coagulopathy and bleeding in severe trauma requires rapid delivery of large amounts of plasma to emergency wards. The resulting need for adequate supplies of nonfrozen or thawed plasma has consequences for storage strategies. Using extensive population data from a setting where both fresh-frozen plasma (FFP) and cold-stored liquid plasma were used, this study investigates whether there is an association between short-term mortality after receipt of FFP or liquid plasma of different storage times. METHODS: A cohort of 84,986 Swedish patients was followed up from first recorded allogenic plasma transfusion for 14-day mortality. Associations with exposure to FFP were expressed as relative risks adjusted for patient characteristics, total transfusions, hospital, and calendar year. For non-FFP, the units given to patients who died and matched patients who survived were compared for their duration of storage. RESULTS: The relative risk of exposure to FFP was 1.19 (95% confidence interval: 1.12-1.27, p < 0.0001), with the risk elevation confined to the earlier calendar years of the study. There was no evidence of any effect of storage time of non-FFP. In analyses of all plasma types, FFP from male donors had lowest risk. CONCLUSIONS: Compared with exclusive use of never-frozen plasma, FFP was associated with increased short-term mortality in the era before leukocyte depletion. FFP from female donors had a significantly higher risk than male FFP. For non-FFP, duration of storage was unrelated to mortality. These findings can help to inform policies for managing high plasma demand in critical care.
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| 31. |
- Nyström, Christine Delisle, et al.
(författare)
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Results From Sweden's 2016 Report Card on Physical Activity for Children and Youth.
- 2016
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Ingår i: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 13:11 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- The 2016 Swedish Report Card on Physical Activity (PA) for Children and Youth is a unique compilation of the existing physical and health related data in Sweden. The aim of this article is to summarize the procedure and results from the report card.Nationally representative surveys and individual studies published between 2005-2015 were included. Eleven PA and health indicators were graded using the Active Healthy Kids Canada grading system. Grades were assigned based on the percentage of children/youth meeting a defined benchmark (A: 81% to 100%, B: 61% to 80%, C: 41% to 60%, D: 21% to 40%, F: 0% to 20%, or incomplete (INC).The assigned grades were Overall Physical Activity, D; Organized Sport Participation, B+; Active Play, INC; Active Transportation, C+; Sedentary Behaviors, C; Family and Peers, INC; School, C+; Community and the Built Environment, B; Government Strategies and Investments, B; Diet, C-; and Obesity, D.The included data provides some support that overall PA is too low and sedentary behavior is too high for almost all age groups in Sweden, even with the many national policies as well as an environment that is favorable to the promotion of PA.
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| 32. |
- Okely, Anthony D., et al.
(författare)
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Cross-sectional examination of 24-hour movement behaviours among 3-and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries : the SUNRISE study protocol
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap. Methods and analysis SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study. Ethics and dissemination The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.
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| 33. |
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| 34. |
- Salim, Agus, et al.
(författare)
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Analysis of incidence and prognosis from 'extreme' case-control designs
- 2014
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Ingår i: Statistics in Medicine. - : Wiley-Blackwell. - 0277-6715 .- 1097-0258. ; 33:30, s. 5388-5398
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Tidskriftsartikel (refereegranskat)abstract
- The significant investment in measuring biomarkers has prompted investigators to improve cost-efficiency by sub-sampling in non-standard study designs. For example, investigators studying prognosis may assume that any differences in biomarkers are likely to be most apparent in an extreme sample of the earliest deaths and the longest-surviving controls. Simple logistic regression analysis of such data does not exploit the information available in the survival time, and statistical methods that model the sampling scheme may be more efficient. We derive likelihood equations that reflect the complex sampling scheme in unmatched and matched extreme' case-control designs. We investigated the performance and power of the method in simulation experiments, with a range of underlying hazard ratios and study sizes. Our proposed method resulted in hazard ratio estimates close to those obtained from the full cohort. The standard error estimates also performed well when compared with the empirical variance. In an application to a study investigating markers for lethal prostate cancer, an extreme case-control sample of lethal cases and the longest-surviving controls provided estimates of the effect of Gleason score in close agreement with analysis of all the data. By using the information in the sampling design, our method enables efficient and valid estimation of the underlying hazard ratio from a study design that is intuitive and easily implemented.
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| 35. |
- Svensson, C, et al.
(författare)
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Maternal Effects for Preterm Birth : A Genetic Epidemiologic Study of 630,000 Families
- 2009
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 170:11, s. 1365-1372
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Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to disentangle the maternal genetic from the fetal genetic effects for preterm birth and to study the possibility of these effects being explained by known risk factors. By cross-linking of the population-based Swedish Multigeneration and Medical Birth registers, 989,027 births between 1992 and 2004 were identified. Alternating logistic regression was applied to model the familial clustering with pairwise odds ratios (PORs), and covariates were included to evaluate if the familial aggregation was explained by exposure to shared risk factors. Generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. Sisters of women who had a preterm delivery had themselves an increased odds of having a preterm delivery (POR = 1.8, 95% confidence interval: 1.5, 2.1), while there was no corresponding increase in odds in families joined by brothers (POR = 1.1, 95% confidence interval: 0.9, 1.4). Twenty-five percent of the variation in preterm birth was explained by maternal genetic factors, whereas fetal genetic factors only marginally influenced the variation in liability. The increased odds ratio between offspring of sisters was independent of maternal risk factors for preterm birth, suggesting that the relative importance of maternal effects is not explained by these well-known risk factors.
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| 36. |
- Tynell, Elsa, et al.
(författare)
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Should plasma from female donors be avoided? : A population-based cohort study of plasma recipients in Sweden from 1990 through 2002
- 2010
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 50:6, s. 1249-1256
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion-related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population-based evidence, policies have already been introduced to exclude female donor plasma. STUDY DESIGN AND METHODS: Short-term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression. RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14-day mortality of 8.43%. Sixty-eight percent were exposed to female plasma, with a 14-day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06-1.27) and 1.32 (CI, 1.17-1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction. CONCLUSIONS: This large population-based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short-term survival disadvantage on recipients.
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| 37. |
- Ullum, Henrik, et al.
(författare)
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Blood donation and blood donor mortality after adjustment for a healthy donor effect
- 2015
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 55:10, s. 2479-2485
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Studies have repeatedly demonstrated that blood donors experience lower mortality than the general population. While this may suggest a beneficial effect of blood donation, it may also reflect the selection of healthy persons into the donor population. To overcome this bias, we investigated the relation between blood donation frequency and mortality within a large cohort of blood donors. In addition, our analyses also took into consideration the effects of presumed health differences linked to donation behavior.STUDY DESIGN AND METHODS Using the Scandinavian Donation and Transfusion database (SCANDAT), we assessed the association between annual number of donations in 5-year windows and donor mortality by means of Poisson regression analysis. The analyses included adjustment for demographic characteristics and for an internal healthy donor effect, estimated among elderly donors exempted from continued donation because of age criteria.RESULTS Statistical analyses included 1,182,495 donors of whom 15,401 died during 9,526,627 person-years of follow-up. Analyses adjusted only for demographic characteristics showed a 18.6% reduction in mortality per additional annual donation (95% confidence interval [CI], 16.8%-20.4%). After additional adjustment for the internal healthy donor effect, each additional annual donation was associated with a 7.5% decreased mortality risk 7.5% (95% CI, 5.7%-9.4%).CONCLUSION We observed an inverse relationship between donation frequency and mortality. The magnitude of the association was reduced after adjustment for an estimate of self-selection in the donor population. Our observations indicate that repeated blood donation is not associated with premature death, but cannot be interpreted as conclusive evidence of a beneficial health effect.
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| 38. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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| 39. |
- Wikman, Agneta Taune, et al.
(författare)
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Noninvasive Single-Exon Fetal RHD Determination in a Routine Screening Program in Early Pregnancy.
- 2012
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Ingår i: Obstetrics and Gynecology. - 1873-233X. ; 120:2, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: : Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: : I.
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