353 research outputs found
Population-based study on the epidemiology of gout
No full textPharmacoepidemiology enables researchers to assess the effects of drugs on outcomes, such as diseases, in large study populations. Furthermore, pharmacoepidemiology is gaining importance in the premarketing phase of the drug development process to provide information on the natural history of the disease the respective drug is being tested for.
Gout is a common, excruciatingly painful, long-known and widely spread inflammatory arthritis characterized by increased serum uric acid levels, and uric acid crystals in the joints (typically in the metatarsophalangeal joint, called podagra. Even though the disease has been long-known and affects about 1.4% to 2.5% of the United Kingdom (UK) population, evidence on many risk factors is lacking. Studies that closely describe the affected population and strengthen existing evidence on risk factors such as drug use are needed to improve treatment and care of affected patients.
The aim of this thesis was to increase the knowledge of gout by providing new information and complementing existing data, and by precisely describing the epidemiology of gout and demographic characteristics, comorbidities, and comedication of the affected population. Furthermore, the goal was to assess the impact of long-known and accepted risk factors in a population-based setting.
The gout project consisted of an epidemiological cohort study, a nested case-control study, and three case-control studies, using data from the Clinical Practice Research Datalink (CPRD). The CPRD is a UK-based general practitioner database containing primary-care records directly entered by general practitioners who do not have any study hypothesis in mind when they record the data. The CPRD population is representative of the UK population in terms of age, sex, geographic distribution, and annual turnover rate. The CPRD is a very useful tool to conduct pharmacoepidemiological research due to its large size, the population-based character of the data, and the opportunity for researchers to gain access to original medical records. However, data on some important confounders such as dietary habits are missing.
All case-control populations of the different gout projects were matched on age, sex, general practice, index date, and history on the CPRD. The overall incidence rate of diagnosed gout in the UK per 10,000 person-years (PYs) was 18.0 (95% CI 17.9-18.1), 29.0 (95% CI 28.8-29.2) in men, and 8.6 (95% CI 8.5-8.8) in women; we further stratified by age, calendar time, region, and seasonality. The nested case-control part of the first project described the study population in terms of demographic characteristics, comorbidities, and comedication. The second project assessed the association between different diuretic drug classes and incident gout. Current use of loop diuretics, thiazide diuretics, and thiazide-like diuretics was associated with a substantially increased risk of incident gout. In the third project, the association between different antidiabetic drug classes, diabetes duration, and diabetes severity and the risk of incident gout was investigated. Increasing glycosylated haemoglobin (A1C) levels were associated with a markedly decreased risk of incident gout in patients with type 2 diabetes mellitus. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. The fourth project assessed the association of hormone replacement therapy with gout, and the effect of timing, duration, and route of administration. Current use of oral opposed oestrogens, but not unopposed oestrogens, was associated with a decreased risk of incident gout in patients without renal failure and was more pronounced in patients with hypertension. The observed risk decrease for gout in users of opposed oestrogens may be explained by the progesterone rather than the oestrogen component.
In summary, these large observational studies of this thesis analysed existing hypotheses and contributed to the evidence of different risk factors for gout such as diuretic drug classes, antidiabetic drugs, diabetes duration and severity, and hormone replacement therapy. Furthermore, several interesting ideas developed in the context of this thesis might be studied in association with gout within the CPRD in near future, to further increase evidence on risk factors associated with the disease, and to improve patient care
A genome-wide association analysis reveals new pathogenic pathways in gout*
No full textGout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024
Modulation of genetic associations with serum urate levels by body-mass-index in humans
No full textWe tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.</p
Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes
No full textThe effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between January 1st, 2015 and December 31st, 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. This study included 43201 patients (median age: 63.23 years old [Interquantile range, IQR]: 55.21-71.95, 53.74% males; SGLTI group: n = 16144; DPP4I group: n = 27057) with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout (Incidence rate [IR]: 2.5; 95% CI: 2.2-2.9) among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8-5.8). SGLT2 was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42-0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42-0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications, and laboratory results. The results remained consistent on competing risk and other propensity score approaches. SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use. [Abstract copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].
Diagnostic Strategies for Gout
No full textGout is a complex form of arthritis and is commonly seen and treated by the primary care provider. When a swollen, red, inflamed metatarsophalangeal joint is seen on exam it is easy to jump to the conclusion of a diagnosis of gout. A single clinical finding of gout is not enough information to diagnose gout. It is important to know what type of fluid is causing the inflamed joint in order to treat it appropriately. A literature search was conducted using the Harley French Library at the University of North Dakota. The author began the search by using two of the most familiar lite rapture d a taxbases in health sciences, Medline (PubMed) and CINAHL. The search was narrowed by using Medical Subject I-leadings (MeSH) terms, limiting the search to RCTs, meta-analysis, sys thematic reviews, and elates of publication within the last eight years. The MeSI-1 search included the the terms gout and synovial fluid. The literature continues to affirm that a synovial joint aspiration is the gold standard for diagnosing gout. It is an immediate procedure that primary care providers should be performing if gout is suspected and can be used to diagnose gout during the intercortical period of the disease
Un nouveau contrôleur de débit d'eau
No full textDescription of a controller for the water flow, without any moving metallic piece.Description d'un contrôleur de débit d'eau ne comportant aucune pièce métallique en mouvement.Gout Robert, Harrichoury Jean-Claude, Lurde Claude. Un nouveau contrôleur de débit d'eau. In: Bulletin de Minéralogie, volume 105, 6, 1982. pp. 697-698
Un nouveau contrôleur de débit d'eau
No full textDescription of a controller for the water flow, without any moving metallic piece.Description d'un contrôleur de débit d'eau ne comportant aucune pièce métallique en mouvement.Gout Robert, Harrichoury Jean-Claude, Lurde Claude. Un nouveau contrôleur de débit d'eau. In: Bulletin de Minéralogie, volume 105, 6, 1982. pp. 697-698
[[alternative]]To explore the dietary and lifestyle risk factors associated with gout by caes-control study.
No full text[[abstract]]Abstract
The purpose of this case-control study was to explore potential dietary and lifestyle risk factors associated with gout. Between 1998-1999, we contacted 236 volunteers from the Gout Clinic in Taipei Municipal Ho-Ping Hospital and volunteers’ coworkers for this study. We conducted face-to-face interviews to collect dietary and lifestyle information by structured questionnaires. Final 92 male patients with gout and 92 controls without gout were included in the analysis.
The results showed that systolic blood pressure, diastolic blood pressure, waist girth, hip girth , triceps skinfold, the times of social dinner events after work were significantly higher in cases than controls. Family history of gout and diabetes mellitus were positively correlated with gout. Consumption of vegetables and fruits were significantly lower in cases than controls. Calcium, iron , folic acid and vitamin C intakes were lower in cases than controls. However, alcohol consumption was significantly higher in cases than controls.
Logistic regression analyses showed that hip girth, waist-hip ratio and systolic blood pressure increased risks for gout. The food sources rich in iron, vitamin B2 , vitamin C and folic acid may be protective for gout .After controlling for covariates including age, family history of gout and diabetes mellitus , education level and systolic blood pressure , we found high waist girth group (>84cm) showed an OR=2.414 compare to the lower group(<84cm). In addition, we found total dietary fiber, iron and folic acid may be protective.
In conclusion, this case-control study in Taiwan confirm that alcohol is the most significant risk for gout. Dietary factors such as total dietary fiber and folic acid may be protective. Waist girth shows a more significant effect than body weight, triceps skinfold and body mass index with gout occurrence .
Dietary changes in patients with diabetes mellitus in combination with gout
No full textTo the report experience of author is driven in relation to the dietary changes in patients with diabetes mellitus (DM) and gout. At combination of gout with type 2 DM a ration consists of limitation of meat and increase of dairies, limitation of carbohydrates only due to simple. People with both gout and DM are advised to avoid foods that may affect the levels of uric acid and insulin in the body. An example of menu of feed is made for a week
Comorbidities in patients with gout in rheumatology clinic Dr. Hasan Sadikin general hospital in 2012 - 2013
No full textGout is a metabolic disease manifested
mainly as an intense monoarticular inflammatory
reaction which is strongly associated with
hyperuricemia. Latest evidence showed that uric acid
exerted effects on the development of other diseases.
Many studies in developed countries had estimated the
frequency of comorbidities associated with gout such
as hypertension, obesity, diabetes mellitus, Chronic
Kidney Disease (CKD), and Myocardial Infarct (MCI).
However, no data regarding these frequencies have
been found in Indonesia up to now to the best of the
author?s knowledge. This study aimed to establish the
frequency of these comorbidities in patients with gout in
Rheumatology Clinic Dr. Hasan Sadikin General Hospital,
Bandung, Indonesia
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