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1.
  • Hudson, Thomas J., et al. (författare)
  • International network of cancer genome projects
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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2.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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3.
  • Aalbers, René, et al. (författare)
  • Randomized, Double-Blind, Dose-Finding Study for Tiotropium when Added to Olodaterol, Administered via the Respimat(®) Inhaler in Patients with Chronic Obstructive Pulmonary Disease.
  • 2015
  • Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 32:9, s. 809-822
  • Tidskriftsartikel (refereegranskat)abstract
    • Combining long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) is beneficial in chronic obstructive pulmonary disease (COPD), as the two classes of bronchodilator have complementary modes of action. The optimal dose for the fixed-dose combination of the LAMA tiotropium and the LABA olodaterol needed to be determined. In this phase II trial, the dose response of tiotropium on top of olodaterol was investigated in a free-dose combination, while other phase II studies have explored different doses of olodaterol on top of tiotropium, with both drugs delivered using the Respimat(®) inhaler.
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4.
  • Beeh, Kai Michael, et al. (författare)
  • Author’s reply
  • 2016
  • Ingår i: International Journal of COPD. - 1176-9106. ; 11:1, s. 2910-2911
  • Tidskriftsartikel (refereegranskat)
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5.
  • Beeh, Kai-Michael, et al. (författare)
  • The lung function profile of once-daily tiotropium and olodaterol via Respimat(®) is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler(®) (ENERGITO(®) study).
  • 2016
  • Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 11, s. 193-205
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens. OBJECTIVE: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD. METHODS: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat(®) and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler(®) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks. RESULTS: Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24). CONCLUSION: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.
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6.
  • Buhl, Roland, et al. (författare)
  • Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).
  • 2015
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 45:4, s. 969-979
  • Tidskriftsartikel (refereegranskat)abstract
    • Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.
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7.
  • Cuni-Sanchez, Aida, et al. (författare)
  • High aboveground carbon stock of African tropical montane forests
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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8.
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9.
  • Enciso-Mora, Victor, et al. (författare)
  • A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1126-1130
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.
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10.
  • Halls, Henry C., et al. (författare)
  • A paleomagnetic and U-Pb geochronology study of the western end of the Grenville dyke swarm: Rapid changes in paleomagnetic field direction at ca. 585 Ma related to polarity reversals?
  • 2015
  • Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 257, s. 137-166
  • Tidskriftsartikel (refereegranskat)abstract
    • A paleomagnetic study of the western end of the similar to 585 Ma Grenville dyke swarm shows that individual dykes are characterized by high coercivity and unblocking temperature magnetizations that can differ in direction by as much as 90 degrees. Field tests including baked contact studies and the continuity of paleomagnetic direction along dyke strike, suggest that the magnetizations are primary. Precise U-Pb baddeleyite dating on these dykes indicates that changes in magnetization direction of similar to 90 degrees occur in less than 4 million years, and their close temporal association with reversals of the axial dipole field suggest that certain dykes are recording an equatorial dipole field as a transitional field between opposite polarity states. The documented instability in the Earth's field occurs less than 10 Myr before the first recorded appearance of macroscopic multi-cellular organisms on Earth, inviting speculation that an extended period of frequent magnetic reversals may play a part in faunal evolution. (C) 2014 Elsevier B.V. All rights reserved.
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11.
  • Hamilton, Calum Alexander, et al. (författare)
  • Plasma biomarkers of neurodegeneration in mild cognitive impairment with Lewy bodies
  • 2023
  • Ingår i: PSYCHOLOGICAL MEDICINE. - 0033-2917 .- 1469-8978. ; 53:16, s. 7865-7873
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma A beta 42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.Methods. Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after >= 1 year. Samples were analysed with a Simoa 4-plex assay for A beta 42, A beta 40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.Results. Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower A beta 42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).Conclusion. Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
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13.
  • Herrick, Ariane L, et al. (författare)
  • Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
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14.
  • Lewthwaite, Hayley, et al. (författare)
  • Predicting the rate of oxygen consumption during the 3-minute constant-rate stair stepping and shuttle tests in people with chronic obstructive pulmonary disease
  • 2020
  • Ingår i: Journal of Thoracic Disease. - : AME Publishing Company. - 2072-1439 .- 2077-6624. ; 12:5, s. 2489-2498
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The 3-minute constant-rate stair stepping (3-min CRSST) and constant-speed shuttle tests (3-min CSST) were developed to assess breathlessness in response to a standardized exercise stimulus. Estimating the rate of oxygen consumption (V'O2) during these tests would assist clinicians to relate the stepping/shuttle speeds that elicit breathlessness to daily physical activities with a similar metabolic demand. This study: (I) developed equations to estimate the V'O2 of these tests in people with chronic obstructive pulmonary disease (COPD); and (II) compared the newly developed and American College of Sports Medicine (ACSM) metabolic equations for estimating the V'O2 of these tests. Methods: This study was a retrospective analysis of people with COPD who completed a 3-min CRSST (n=98) or 3-min CSST (n=69). Multivariate linear regression estimated predictors (alpha <0.05) of V'O2 to construct COPD-specific metabolic equations. The mean squared error (MSE) of the COPD-specific and ACSM equations was calculated and compared. Bland-Altman analyses evaluated level of agreement between measured and predicted V'O2 using each equation; limits of agreement (LoA) and patterns of bias were compared. Results: Stepping rate/shuttle speed and body mass were identified as significant predictors of V'O2. The MSE of the COPD-specific equations was 0.05 L.min?1 for both tests. Mean difference between measured and predicted V'O2 was 0.00 L.min?1 (95% LoA ?0.46, 0.46) and 0.00 L.min?1 (95% LoA ?0.44, 0.44) for the 3-min CRSST and 3-min CSST, respectively. For the ACSM metabolic equations, the MSE was 0.10 L.min?1 and 0.18 L.min?1 for the 3-min CRSST and 3-min CSST, respectively. The ACSM metabolic equations underestimated V'O2 of the 3-min CRSST by ?0.18 L.min?1 (95% LoA ?0.68, 0.32), and overestimated V'O2 of the 3-min CSST by 0.35 L.min?1 (95% LoA ?0.14, 0.84). Conclusions: This study presents metabolic equations to predict V'O2 of the 3-min CRSST and 3-min CSST for people with COPD that are more accurate than the ACSM metabolic equations.
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15.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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16.
  • Mullins, Niamh, et al. (författare)
  • GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
  • 2019
  • Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 176:8, s. 651-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.
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17.
  • Peytrignet, Sébastien, et al. (författare)
  • Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.
  • 2018
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 57:2, s. 370-381
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
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18.
  • Stanway, James, et al. (författare)
  • IgA vasculitis nephritis-outcomes in adult-onset disease
  • 2024
  • Ingår i: Rheumatology. - : OXFORD UNIV PRESS. - 1462-0324 .- 1462-0332.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle-aged adults (35-64) and elderly patients (>= 64 years) focusing on kidney outcomes. Methods: We identified patients with renal biopsy-confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. Results: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% elderly (>64 years). Median follow-up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle-aged (13.7%) and younger adults (2.9%) (chi(2 )11.6, P = 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and estimated glomerular filtration rate < 30 ml/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. Conclusion: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.
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