| 1. |
- Turcot, Valerie, et al.
(author)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Journal article (peer-reviewed)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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| 2. |
- Wessel, Jennifer, et al.
(author)
-
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Journal article (peer-reviewed)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 3. |
- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
-
In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
-
Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 4. |
- Bedard, Annabelle, et al.
(author)
-
Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
- 2019
-
In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
-
Journal article (peer-reviewed)abstract
- Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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| 5. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
-
In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
-
Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 6. |
- Bousquet, J. Jean, et al.
(author)
-
Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
-
In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
-
Research review (peer-reviewed)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 7. |
- Christopoulos, Arthur, et al.
(author)
-
THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
-
In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
-
Research review (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 8. |
- Costa Storti, Claudia, et al.
(author)
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The Double Effect of COVID-19 Confinement Measures and Economic Recession on High-Risk Drug Users and Drug Services.
- 2021
-
In: European Addiction Research. - : S. Karger. - 1022-6877 .- 1421-9891. ; 27, s. 239-241
-
Journal article (other academic/artistic)abstract
- The ongoing COVID-19 pandemic is likely to have a profound impact on the lives of high-risk drug users and on the services responding to their needs in at least two important ways: first, through the restrictive measures introduced to mitigate the spread of the virus and, second, as a result of extensive economic downturn. Currently there is great uncertainty as to the future intensity and duration of the pandemic. In addition, the lessons we have been able to learn from previous economic downturns may be of limited applicability to the current situation, which differs in a number of significant respects. Experience nevertheless suggests that the potential consequences for drug users' health and well-being may be severe. The ongoing uncertainty serves to underline the importance of close monitoring of the drug situation and preparing flexible and innovative solutions to be able to meet new challenges which may arise.
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| 9. |
- Couch, Fergus J., et al.
(author)
-
Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
-
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
-
Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 10. |
- Gao, Hong, et al.
(author)
-
The landscape of tolerated genetic variation in humans and primates
- 2023
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
-
Journal article (peer-reviewed)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 11. |
- Hallan, Andreas, et al.
(author)
-
Risk factors on the development of new-onset gastroesophageal reflux symptoms : a population-based prospective cohort study : the HUNT study
- 2015
-
In: The American Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9270 .- 1572-0241.
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Gastroesophageal reflux disease (GERD) is a highly prevalent disorder. This study assessed the risk factors of new-onset gastroesophageal reflux symptoms (GERS). METHODS: The study was based on the HUNT study, a prospective population-based cohort study conducted in 1995-1997 and 2006-2009 in Nord-Trondelag County, Norway. All inhabitants from 20 years of age were invited. Risk factors of new-onset heartburn or acid regurgitation were examined using logistic regression, providing odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 29,610 individuals were included (61% response rate). Participants reporting no GERS at baseline and severe GERS at follow-up (new-onset GERS; n=510) were compared with participants reporting no complaints at both times (n=14,406). Increasing age (OR 1.01 per year, 95% CI 1.00-1.02) was positively associated, whereas male sex (OR 0.81, 95% CI 0.66-0.98) and higher education (OR 0.69, 95% CI 0.56-0.86) were negatively associated with new-onset GERS. Gain in body mass index (BMI) was dose-dependently associated with new-onset GERS (OR 1.30 per unit increase in BMI, 95% CI 1.25-1.35), irrespective of baseline BMI. Previous and current tobacco smoking were associated with new-onset GERS (OR 1.37, 95% CI 1.07-1.76 and OR 1.29, 95% CI 1.00-1.67, respectively). Tobacco smoking cessation was associated with new-onset GERS among those with gain in BMI upon quitting (OR 2.03, 95% CI 1.31-3.16, with >3.5 BMI units increase). CONCLUSIONS: New-onset GERS were associated with increasing age, female sex, lower education, gain in BMI, and ever tobacco smoking. Tobacco smoking cessation was associated with new-onset GERS among those who gained weight upon quitting.
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| 12. |
- Hellner, Britt Marie, et al.
(author)
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Systematiskt arbete för äldres säkerhet : om fall, trafikolyckor och bränder
- 2007
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Book (peer-reviewed)abstract
- Äldre personer är överrepresenterade i nästan alla olyckor. Förutom stort personligt lidande för individen leder skadorna ofta till omfattande kostnader för samhället. Därför har Räddningsverket och IMS/Socialstyrelsen tilsammans med forskare vid Umeå Universitet, Karlstad Universitet, Krolinska Insitutet, FoU Välfärd Örebro samt Vägverket gemensamt sammaställt denna bok. Syftet är att inspirera och vägleda ett systematiskt arbete i samhället för att öka säkerheten och minska skadorna till följd av olyckor bland äldre. Boken riktar sig till verksamma inom vård och omsorg för äldre, tjänstemän och politiker på olika nivåer i samhället
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| 13. |
- Jensen, Jane, et al.
(author)
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Effects of a fall prevention program including exercise on mobility and falls in frail older people living in residential care facilities
- 2004
-
In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 16:4, s. 283-92
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Impaired mobility is one of the strongest predictors for falls in older people. We hypothesized that exercise as part of a fall prevention program would have positive effects, both short- and long-term, on gait, balance and strength in older people at high risk of falling and with varying levels of cognition, residing in residential care facilities. A secondary hypothesis was that these effects would be associated with a reduced risk of falling. METHODS: 187 out of all residents living in 9 facilities, > or =65 years of age were at high risk of falling. The facilities were cluster-randomized to fall intervention or usual care. The intervention program comprised: education, environment, individually designed exercise, drug review, post-fall assessments, aids, and hip protectors. Data were adjusted for baseline performance and clustering. RESULTS: At 11 weeks, positive intervention effects were found on independent ambulation (FAC, p=0.026), maximum gait speed (p=0.002), and step height (> or =10 cm, p<0.001), but not significantly on the Berg Balance Scale. At 9 months (long-term outcome), 3 intervention and 15 control residents had lost the ability to walk (p=0.001). Independent ambulation and maximum gait speed were maintained in the intervention group but deteriorated in the control group (p=0.001). Residents with both higher and lower cognition benefited in most outcome measures. Noassociation was found between improved mobility and reduced risk of falling.CONCLUSIONS: Exercise, as part of a fall prevention program, appears to preserve the ability to walk, maintain gait speed, ambulate independently, and improve step height. Benefits were found in residents with both lower and higher cognitive impairment, but were not found to be associated with a reduced risk of falling
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| 14. |
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| 15. |
- Jensen, Jane, et al.
(author)
-
Fall and injury prevention in older people living in residential care facilities : A cluster randomized trial
- 2002
-
In: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 136:10, s. 733-41
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Falls and resulting injuries are particularly common in older people living in residential care facilities, but knowledge about the prevention of falls is limited. OBJECTIVE: To investigate whether a multifactorial intervention program would reduce falls and fall-related injuries. DESIGN: A cluster randomized, controlled, nonblinded trial. SETTING: 9 residential care facilities located in a northern Swedish city. PATIENTS: 439 residents 65 years of age or older. INTERVENTION: An 11-week multidisciplinary program that included both general and resident-specific, tailored strategies. The strategies comprised educating staff, modifying the environment, implementing exercise programs, supplying and repairing aids, reviewing drug regimens, providing free hip protectors, having post-fall problem-solving conferences, and guiding staff. MEASUREMENTS: The primary outcomes were the number of residents sustaining a fall, the number of falls, and the time to occurrence of the first fall. A secondary outcome was the number of injuries resulting from falls. RESULTS: During the 34-week follow-up period, 82 residents (44%) in the intervention program sustained a fall compared with 109 residents (56%) in the control group (risk ratio, 0.78 [95% CI, 0.64 to 0.96]). The adjusted odds ratio was 0.49 (CI, 0.37 to 0.65), and the adjusted incidence rate ratio of falls was 0.60 (CI, 0.50 to 0.73). Each of 3 residents in the intervention group and 12 in the control group had 1 femoral fracture (adjusted odds ratio, 0.23 [CI, 0.06 to 0.94]). Clustering was considered in all regression models. CONCLUSION: An interdisciplinary and multifactorial prevention program targeting residents, staff, and the environment may reduce falls and femoral fractures.
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| 16. |
- Jensen, Jane, et al.
(author)
-
Fall and injury prevention in residential care : effects in residents with higher and lower levels of cognition
- 2003
-
In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 51:5, s. 627-35
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the effectiveness of a multifactorial fall and injury prevention program in older people with higher and lower levels of cognition. DESIGN: A preplanned subgroup comparison of the effectiveness of a cluster-randomized, nonblinded, usual-care, controlled trial.SETTING: Nine residential facilities in Umea, Sweden. PARTICIPANTS: All consenting residents living in the facilities, aged 65 and older, who could be assessed using the Mini-Mental State Examination (MMSE; n = 378).An MMSE score of 19 was used to divide the sample into one group with lower and one with higher level of cognition. The lower MMSE group was older (mean +/- standard deviation = 83.9 +/- 5.8 vs 82.2 +/- 7.5) and more functionally impaired (Barthel Index, median (interquartile range) 11 (6-15) vs 17 (13-18)) and had a higher risk of falling (64% vs 36%) than the higher MMSE group. INTERVENTION: A multifactorial fall prevention program comprising staff education, environmental adjustment, exercise, drug review, aids, hip protectors, and postfall problem-solving conferences. MEASUREMENTS: The number of falls, time to first fall, and number of injuries were evaluated and compared by study group (intervention vs control) and by MMSE group. RESULTS: A significant intervention effect on falls appeared in the higher MMSE group but not in the lower MMSE group (adjusted incidence rates ratio of falls P =.016 and P =.121 and adjusted hazard ratio P <.001 and P =.420, respectively). In the lower MMSE group, 10 femoral fractures were found, all of which occurred in the control group (P =.006). CONCLUSION: The higher MMSE group experienced fewer falls after this multifactorial intervention program, whereas the lower MMSE group did not respond as well to the intervention, but femoral fractures were reduced in the lower MMSE group
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| 17. |
- Jensen, Jane, et al.
(author)
-
Falls among frail older people in residential care
- 2002
-
In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 30:1, s. 54-61
-
Journal article (peer-reviewed)abstract
- Aims: A prospective study was carried out to investigate the incidence, circumstances, and injuries from falls among frail older people living in three different types of Swedish residential care settings. Methods: The settings were senior citizens' apartments, an old people's home, and a group dwelling for people with dementia. The falls were registered during the three-year study period on a semi-structured fall report, and injurious falls were categorized according to severity. Results: In total 428 falls occurred among 121 residents. The incidence rate of falls at the group dwelling was twice the rates of the old people's home and senior citizens' apartments (4282 compared with 1709 and 2114 falls per 1000 person-years respectively). Some 27% of the falls occurred during the night (2100 h to 0600 h) and 28% were related to a visit to the lavatory. The presence of acute disease at the time of a fall was diagnosed in 23% of the falls. Some type of injury occurred in 118 falls (28%) and 36 of these (8%) led to moderate or serious injuries. In total 48 fractures were diagnosed. Conclusions: In a preventive programme for falls and injuries in residential care settings, areas of particular interest should include falls after mealtimes and falls at night, conditions of acute diseases, rising up from sitting, walking, and activities in progress, especially visits to the lavatory.
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| 18. |
- Justice, Anne E., et al.
(author)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Journal article (peer-reviewed)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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| 19. |
- Kallin, Kristina, et al.
(author)
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Predisposing and precipitating factors for falls among older people in residential care
- 2002
-
In: Public Health. - 0033-3506 .- 1476-5616. ; 116:5, s. 263-271
-
Journal article (peer-reviewed)abstract
- Falls and their consequences are serious health problems among older populations. To study predisposing and precipitating factors for falls among older people in residential care we used a cross-sectional study design with a prospective follow up for falls. Fifty-eight women and 25 men, with a mean age of 79.6 y, were included and prospectively followed up regarding falls for a period of 1 y after baseline assessments. All those who fell were assessed regarding factors that might have precipitated the fall. The incidence rate was 2.29 falls/person years. Antidepressants (selective serotonin reuptake inhibitors, SSRIs), impaired vision and being unable to use stairs without assistance were independently associated with being a 'faller'. Twenty-eight (53.8%) of the fallers suffered injuries as a result of their falls, including 21 fractures. Twenty-seven percent of the falls were judged to be precipitated by an acute illness or disease and 8.6% by a side effect of a drug. Acute symptoms of diseases or drug side effects were associated with 58% of the falls which resulted in fractures. We conclude that SSRIs seem to constitute one important factor that predisposes older people to fall, once or repeatedly. Since acute illnesses and drug side-effects were important precipitating factors, falls should be regarded as a possible symptom of disease or a side-effect of a drug until it is proven otherwise.
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| 20. |
- Kallin, Kristina, et al.
(author)
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Why the elderly fall in residential care facilities, and suggested remedies.
- 2004
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In: The Journal of family practice. - 0094-3509 .- 1533-7294. ; 53:1, s. 41-52
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To study precipitating factors for falls among older people living in residential care facilities. DESIGN: Prospective cohort study. SETTING: Five residential care facilities. PARTICIPANTS: 140 women and 59 men, mean age +/- SD 82.4 +/- 6.8 (range, 65-97). MEASUREMENTS: After baseline assessments, falls in the population were tracked for 1 year. A physician, a nurse, and a physiotherapist investigated each event, and reached a consensus concerning the most probable precipitating factors for the fall. RESULTS: Previous falls and treatment with antidepressants were found to be the most important predisposing factors for falls. Probable precipitating factors could be determined in 331 (68.7%) of the 482 registered falls. Acute disease or symptoms of disease were judged to be precipitating, alone or in combination in 186 (38.6%) of all falls; delirium was a factor in 48 falls (10.0%), and infection, most often urinary tract infection, was a factor in 38 falls (7.9%). Benzodiazepines or neuroleptics were involved in the majority of the 37 falls (7.7%) precipitated by drugs. External factors, such as material defects and obstacles, precipitated 38 (7.9%) of the falls. Other conditions both related to the individual and the environment, such as misinterpretation (eg, overestimation of capacity or forgetfulness), misuse of a roller walker, or mistakes made by the staff were precipitating factors in 83 (17.2%) of falls. CONCLUSION: Among older people in residential care facilities, acute diseases and side effects of drugs are important precipitating factors for falls. Falls should therefore be regarded as a possible symptom of disease or a drug side effect until proven otherwise. Timely correction of precipitating and predisposing factors will help prevent further falls.
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| 21. |
- Kuderna, Lukas F. K., et al.
(author)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
-
Journal article (peer-reviewed)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 22. |
- Kuderna, Lukas F. K., et al.
(author)
-
Identification of constrained sequence elements across 239 primate genomes
- 2024
-
In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
-
Journal article (peer-reviewed)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 23. |
- Lie, Tina Malene, et al.
(author)
-
Snus and risk of gastroesophageal reflux : a population-based case-control study : the HUNT study
- 2017
-
In: Scandinavian Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0036-5521 .- 1502-7708.
-
Journal article (peer-reviewed)abstract
- Objective: Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS). Material and Methods: The study was based on the third Nord-Trøndelag health study (HUNT3), a population-based study of all adult residents in Nord-Trøndelag County, Norway, performed in 2006−2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression. Results: Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% CI 0.64−0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00−1.46 and 1.41, 95% CI 1.02−1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02−2.16), while those aged between 50−60 and 60−70 years had a reduced risk (OR 0.67, 95% CI 0.49−0.93 and 0.51, 95% CI 0.28−0.94, respectively). Conclusions: Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.
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| 24. |
- Lundin-Olsson, Lillemor, et al.
(author)
-
Predicting falls in residential care by a risk assessment tool, staff judgement, and history of falls
- 2003
-
In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 15:1, s. 51-59
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: It is of great importance to consider whether a tool's predictive value is generalizable to similar samples in other locations. Numerous fall prediction systems have been developed, but very few are evaluated over a different time period in a different location. The purpose of this study was to validate the predictive accuracy of the Mobility Interaction Fall (MIF) chart, and to compare it to staff judgement of fall risk and history of falls. METHODS: The MIF chart, staff judgement, and fall history were used to classify the risk of falling in 208 residents (mean age 83.2 +/- 6.8 years) living in four residential care facilities in northern Sweden. The MIF chart includes an observation of the ability to walk and simultaneously interact with a person or an object, a vision test, and a concentration rating. Staff rated each resident's risk as high or low and reported the resident's history of falls during the past 6 months. Falls were followed up for 6 months. RESULTS: During the follow-up period, 104 residents (50%) fell at least once indoors. Many of the factors commonly associated with falls did not differ significantly between residents who fell at least once and residents who did not fall. In this validating sample the predictive accuracy of the MIF chart was notably lower than in the developmental sample. A combination of any two of the MIF chart, staff judgement, and history of falls was more accurate than any approach alone; more than half of the residents classified as 'high risk' by two approaches sustained a fall within 3 months. CONCLUSIONS: Residents classified as 'high risk' by any two of the MIF chart, staff judgement, and history of falls should be regarded as particularly prone to falling and in urgent need of preventive measures.
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| 25. |
- Machalek, Dorothy A., et al.
(author)
-
Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium : a systematic review and meta-analysis
- 2020
-
In: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 20:11, s. 1302-1314
-
Research review (peer-reviewed)abstract
- BACKGROUND: Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location.METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370.RESULTS: Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8-42·5); prevalence increased from 10·0% (95% CI 2·6-20·1%) before 2010, to 51·4% (40·3-62·4%) in 2016-17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5-11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3-4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region.INTERPRETATION: Global surveillance and measures to optimise the efficacy of treatments-including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches-are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains.
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| 26. |
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| 27. |
- Meng, Weihua, et al.
(author)
-
A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes
- 2018
-
In: Acta Ophthalmologica. - : Wiley. - 1755-375X. ; 96:7, s. 811-819
-
Journal article (peer-reviewed)abstract
- Purpose: Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. Methods: A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts. Results: Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10−9. Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10−8 and 1.23 × 10−8, respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429). Conclusion: This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.
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| 28. |
- Muraro, Antonella, et al.
(author)
-
Managing food allergy: GA2LEN guideline 2022.
- 2022
-
In: The World Allergy Organization journal. - : Elsevier BV. - 1939-4551. ; 15:9
-
Journal article (peer-reviewed)abstract
- Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.
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| 29. |
- Naghavi, Mohsen, et al.
(author)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
-
Journal article (peer-reviewed)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 30. |
- Nordin, Ellinor, et al.
(author)
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Prognostic validity of the Timed Up-and-Go test : a modified Get-Up-and-Go test, staff's global judgement and fall history in evaluating fall risk in residential care facilities
- 2008
-
In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 37:4, s. 442-448
-
Journal article (peer-reviewed)abstract
- Objectives: to evaluate and compare the prognostic validity relative to falls of the Timed Up-and-Go test (TUG), a modified Get-Up-and-Go test (GUG-m), staff's judgement of global rating of fall risk (GLORF) and fall history among frail older people. Design: cohort study, 6-month prospective follow-up for falls. Participants: 183 frail persons living in residential care facilities in Sweden, mean age 84 years, 73% women. Methods: the occurrence of falls during the follow-up period were compared to the following assessments at baseline: the TUG at normal speed; the GUG-m, a rating of fall risk scored from 1 (no risk) to 5 (very high risk); the GLORF, staff's rating of fall risk as 'high' or 'low'; a history of falls in the previous 6 months. These assessment tools were evaluated using sensitivity, specificity and positive and negative likelihood ratios (LR+ to rule in and LR- to rule out a high fall risk). Results: 53% of the participants fell at least once. Various cut-off values of the TUG (12, 15, 20, 25, 30, 35, 40 s) and the GUG-m showed LR+ between 0.9 and 2.6 and LR- between 0.1 and 1.0. The GLORF showed an LR+ of 2.8 and an LR- of 0.6 and fall history showed an LR+ of 2.4 and an LR- of 0.6. Conclusions: in this population of frail older people, staff judgement of their residents' fall risk as well as previous falls both appear superior to the performance-based measures TUG and GUG-m in ruling in a high fall risk. A TUG score of less than 15 s gives guidance in ruling out a high fall risk but insufficient information in ruling in such a risk. The grading of fall risk by GUG-m appears of very limited value.
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| 31. |
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| 32. |
- Nyberg, Lars, et al.
(author)
-
Fall-olyckor kan förebyggas
- 1999
-
In: Sjukgymnasten. - 0037-6019. ; :2, s. 18-24
-
Journal article (other academic/artistic)
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| 33. |
- Prescott, Eva, et al.
(author)
-
Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
- 2022
-
In: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 365, s. 34-40
-
Journal article (peer-reviewed)abstract
- Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.Patients 7-28days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade≥2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200mg or 50mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.Of 129 randomized patients, 128 received treatment (200mg, n=52; 50mg, n=25; placebo, n=51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200mg, 50mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.gov identifier: NCT03317002.
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| 34. |
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| 35. |
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| 36. |
- Rosendahl, Erik, et al.
(author)
-
Prediction of falls among older people in residential care facilities by the Downton index
- 2003
-
In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 15:2, s. 142-7
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Falls are frequent among older people living in residential care facilities. The aim of this study was to investigate the prediction accuracy of the Downton fall risk index among older people living in residential care facilities at 3, 6 and 12 months, and with two different definitions of falls. METHODS: Seventy-eight residents in one residential care facility, 56 women and 22 men, mean +/- SD age 81 +/- 6 years, participated in this study. Forty-seven percent of participants had dementia, 45% depression, and 32% previous stroke. Forty-one percent of participants used a walking device indoors, and the median score of the Barthel ADL Index was 16. At baseline, the Downton fall risk index was scored for each individual. A score of 3 or more was taken to indicate high risk of falls. Participants were followed up prospectively for 12 months, with regard to falls indoors. RESULTS: At 3, 6 and 12 months, and using a fall definition including all indoor falls, sensitivity ranged from 81 to 95% with the highest value at 3 months, and specificity ranged from 35 to 40%. The prognostic separation values ranged from 0.26 to 0.37. Within 3 months, the risk of falling was 36% in the high-risk group (index score > or = 3) and 5% in the low-risk group. The accuracy of predictions did not improve when applying a fall definition in which falls precipitated by acute illness, acute disease, or drug side-effects were excluded. CONCLUSIONS: Already after 3 months, the Downton fall risk index appears to be a useful tool for predicting falls, irrespective of their cause, among older people in residential care facilities
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| 37. |
- Rosendahl, Erik, et al.
(author)
-
Prediction of falls among older people in residential care facilities by the Downton index
- 2002
-
In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 15:2, s. 142-147
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Falls are frequent among older people living in residential care facilities. The aim of this study was to investigate the prediction accuracy of the Downton fall risk index among older people living in residential care facilities at 3, 6 and 12 months, and with two different definitions of falls. METHODS: Seventy-eight residents in one residential care facility, 56 women and 22 men, mean +/- SD age 81 +/- 6 years, participated in this study. Forty-seven percent of participants had dementia, 45% depression, and 32% previous stroke. Forty-one percent of participants used a walking device indoors, and the median score of the Barthel ADL Index was 16. At baseline, the Downton fall risk index was scored for each individual. A score of 3 or more was taken to indicate high risk of falls. Participants were followed up prospectively for 12 months, with regard to falls indoors. RESULTS: At 3, 6 and 12 months, and using a fall definition including all indoor falls, sensitivity ranged from 81 to 95% with the highest value at 3 months, and specificity ranged from 35 to 40%. The prognostic separation values ranged from 0.26 to 0.37. Within 3 months, the risk of falling was 36% in the high-risk group (index score > or = 3) and 5% in the low-risk group. The accuracy of predictions did not improve when applying a fall definition in which falls precipitated by acute illness, acute disease, or drug side-effects were excluded. CONCLUSIONS: Already after 3 months, the Downton fall risk index appears to be a useful tool for predicting falls, irrespective of their cause, among older people in residential care facilities.
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| 38. |
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| 39. |
- Sivertsson, Louise, et al.
(author)
-
Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor
- 2013
-
In: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 22:4, s. 581-594
-
Journal article (peer-reviewed)abstract
- Drug-induced liver injury is a serious and frequently occurring adverse drug reaction in the clinics and is hard to predict during preclinical studies. Today, primary hepatocytes are the most frequently used cell model for drug discovery and prediction of toxicity. However, their use is marred by high donor variability regarding drug metabolism and toxicity, and instable expression levels of liver-specific genes such as cytochromes P450. An in vitro model system based on human embryonic stem cells (hESC), with their unique properties of pluripotency and self-renewal, has potential to provide a stable and unlimited supply of human hepatocytes. Much effort has been made to direct hESC toward the hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results are encouraging, these cells lack important functionality. Here, we investigate if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D) bioreactor system. Human ESCs were differentiated toward the hepatic lineage using the same cells in either the 3D or 2D system. A global transcriptional analysis identified important differences between the 2 differentiation regimes, and we identified 10 pathways, highly related to liver functions, which were significantly upregulated in cells differentiated in the bioreactor compared to 2D control cultures. The enhanced hepatic differentiation observed in the bioreactor system was also supported by immunocytochemistry. Taken together, our results suggest that hepatic differentiation of hESC is improved when using this 3D bioreactor technology as compared to 2D culture systems.
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| 40. |
- Sousa-Pinto, Bernardo, et al.
(author)
-
Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®
- 2021
-
In: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 11:7
-
Research review (peer-reviewed)abstract
- Background: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs.Methods: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or “VAS Work” indicating clinical change.Results: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness.Conclusion: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.
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| 41. |
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| 42. |
- Surendran, Praveen, et al.
(author)
-
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 43. |
- von Heideken Wågert, Petra, et al.
(author)
-
Falls in very old people : the population-based Umeå 85+ Study
- 2009
-
In: Archives of gerontology and geriatrics (Print). - Clare : Elsevier. - 0167-4943 .- 1872-6976. ; 49, s. 390-396
-
Journal article (peer-reviewed)abstract
- The aim of this study was to describe incidences of falls and fall-related injuries, and to identify predisposing factors for falls in very old people in a prospective population-based follow-up study for falls. The study is part of the Umeå 85+ Study which includes half of the population aged 85, and the total population aged 90 and ≥95 (−103), in Umeå, Sweden. Of the 253 people interviewed, 220 (87%) were followed up for falls for 6 months, of whom 109 lived in ordinary and 111 in institutional housing. A comprehensive geriatric baseline assessment was made through interviews and testing during home visits. Forty percent of the participants did fall a total 304 times, corresponding to 2.17 falls per Person Year (PY). It occurred 0.83 injuries per PY, including 0.14 fractures per PY. In a Cox regression analysis, the independent explanatory risk factors for time to first fall were dependency in activities of daily living (ADL), thyroid disorders, treatment with selective serotonin reuptake inhibitors (SSRIs) and occurrence of falls in the preceding year. It could be predicted that every seventh participant and every third of the people who did fall would suffer a fracture within 1 year. ADL, thyroid disorders and treatment with SSRIs should be considered in fall prevention programmes.
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| 44. |
- Weller, David, et al.
(author)
-
An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership : Survey development and implementation
- 2016
-
In: BMJ Open. - : BMJ. - 2044-6055. ; 6:7
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Journal article (peer-reviewed)abstract
- This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses. Design and setting: Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions. Participants: Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients' PCPs and cancer treatment specialists (CTSs) are surveyed, and 'data rules' are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases. Main outcomes: Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types. Conclusion: An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.
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| 45. |
- Winkel, Per, et al.
(author)
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A screening method to spot biomarkers that may warn of serious events in a chronic disease - illustrated by cardiological CLARICOR trial data
- 2021
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 59:11, s. 1852-1860
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker's clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable.METHODS: The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient's entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers.RESULTS: Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes.CONCLUSIONS: For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.
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| 46. |
- Zeng, Chenjie, et al.
(author)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Journal article (peer-reviewed)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 47. |
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- 2019
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Journal article (peer-reviewed)
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