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      Comorbidities in patients with gout prior to and following diagnosis: case-control study

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          Abstract

          Objectives

          To determine the burden of comorbidities in patients with gout at diagnosis and the risk of developing new comorbidities post diagnosis.

          Methods

          There were 39 111 patients with incident gout and 39 111 matched controls identified from the UK Clinical Practice Research Data-link. The risk of comorbidity before (ORs) and after the diagnosis of gout (HRs) were estimated, adjusted for age, sex, diagnosis year, body mass index, smoking and alcohol consumption.

          Results

          Gout was associated with adjusted ORs (95% CIs) of 1.39 (1.34 to 1.45), 1.89 (1.76 to 2.03) and 2.51 (2.19 to 2.86) for the Charlson index of 1–2, 3–4 and ≥5, respectively. Cardiovascular and genitourinary diseases, in addition to hyperlipidaemia, hypothyroidism, anaemia, psoriasis, chronic pulmonary diseases, osteoarthritis and depression, were associated with a higher risk for gout. Gout was also associated with an adjusted HR (95% CI) of 1.41 (1.34 to 1.48) for having a Charlson index ≥1. Median time to first comorbidity was 43 months in cases and 111 months in controls. Risks for incident comorbidity were higher in cardiovascular, genitourinary, metabolic/endocrine and musculoskeletal diseases, in addition to liver diseases, hemiplegia, depression, anaemia and psoriasis in patients with gout. After additionally adjusting for all comorbidities at diagnosis, gout was associated with a HR (95% CI) for all-cause mortality of 1.13 (1.08 to 1.18; p<0.001).

          Conclusions

          The majority of patients with gout have worse pre-existing health status at diagnosis and the risk of incident comorbidity continues to rise following diagnosis. The range of associated comorbidities is broader than previously recognised and merits further evaluation.

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          Most cited references59

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          Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

          During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
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            Validity of diagnostic coding within the General Practice Research Database: a systematic review.

            The UK-based General Practice Research Database (GPRD) is a valuable source of longitudinal primary care records and is increasingly used for epidemiological research. To conduct a systematic review of the literature on accuracy and completeness of diagnostic coding in the GPRD. Systematic review. Six electronic databases were searched using search terms relating to the GPRD, in association with terms synonymous with validity, accuracy, concordance, and recording. A positive predictive value was calculated for each diagnosis that considered a comparison with a gold standard. Studies were also considered that compared the GPRD with other databases and national statistics. A total of 49 papers are included in this review. Forty papers conducted validation of a clinical diagnosis in the GPRD. When assessed against a gold standard (validation using GP questionnaire, primary care medical records, or hospital correspondence), most of the diagnoses were accurately recorded in the patient electronic record. Acute conditions were not as well recorded, with positive predictive values lower than 50%. Twelve papers compared prevalence or consultation rates in the GPRD against other primary care databases or national statistics. Generally, there was good agreement between disease prevalence and consultation rates between the GPRD and other datasets; however, rates of diabetes and musculoskeletal conditions were underestimated in the GPRD. Most of the diagnoses coded in the GPRD are well recorded. Researchers using the GPRD may want to consider how well the disease of interest is recorded before planning research, and consider how to optimise the identification of clinical events.
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              Elevated uric acid increases the risk for kidney disease.

              Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease, but it is unclear whether uric acid is an independent risk factor. In this study, data from 21,475 healthy volunteers who were followed prospectively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease (estimated GFR [eGFR] or =9.0 mg/dl) was associated with a tripled risk (odds ratio 3.12; 95% confidence interval 2.29 to 4.25). These increases in risk remained significant even after adjustment for baseline eGFR, gender, age, antihypertensive drugs, and components of the metabolic syndrome (waist circumference, HDL cholesterol, blood glucose, triglycerides, and BP). In a fully adjusted spline model, the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men; above these levels, the associated risk increased rapidly. In conclusion, elevated levels of uric acid independently increase the risk for new-onset kidney disease.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann. Rheum. Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                January 2016
                14 November 2014
                : 75
                : 1
                : 210-217
                Affiliations
                [1 ]Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham , Nottingham, UK
                [2 ]Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital , Taoyuan, Taiwan
                [3 ]Division of Epidemiology and Public Health, School of Medicine, University of Nottingham , Nottingham, UK
                [4 ]Arthritis Research UK Primary Care Centre, Keele University , Keele, UK
                Author notes

                Handling editor Tore K Kvien

                [Correspondence to ] Dr Weiya Zhang, Academic Rheumatology, Clinical Sciences Building, City Hospital, Nottingham NG51PB, UK; weiya.zhang@ 123456nottingham.ac.uk

                Joint senior authors: WZ and MD.

                Article
                annrheumdis-2014-206410
                10.1136/annrheumdis-2014-206410
                4717388
                25398375
                4fd51d7a-7482-455d-b6d3-f2c6c09a18dc
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 4 August 2014
                : 13 October 2014
                : 26 October 2014
                Categories
                1506
                Clinical and Epidemiological Research
                Extended report
                Custom metadata
                unlocked

                Immunology
                gout,epidemiology,cardiovascular disease
                Immunology
                gout, epidemiology, cardiovascular disease

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