Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.
WHAT DO WE WANT TO KNOW?: Delayed diagnosis results in serious consequences for patients and healthcare professionals and can incur substantial financial costs. While research focusing upon cancer suggests that late diagnosis leads to increased morbidity and mortality, the evidence for other conditions is less clear. This systematic rapid evidence assessment (SREA) identifies the nature and extent of the literature on late diagnosis across a range of conditions. We wanted to know:
1. What is the prevalence of late diagnosis?
2. What are the determinants of late diagnosis?
3. What are the outcomes of late diagnosis?
4. What are the cost implications of late diagnosis?
5. Which interventions reduce delays in diagnosis?
WHO WANTS TO KNOW?: Policy makers, clinicians, general practitioners and patients. WHAT DID WE FIND?: • Late diagnosis is of most concern for those with chronic obstructive pulmonary disease (COPD), dementia, human immunodeficiency virus (HIV) and type 1 Diabetes.
• COPD has a high prevalence of late diagnosis, with an estimated 80% of cases remaining undiagnosed. Many of these cases are patients in the milder stages of the disease.
• Early dementia is harder to detect, with doctors acknowledging their difficulties in distinguishing between dementia and ‘normal ageing’.
• The evidence suggested that a substantial proportion (16–51%) of children experience delayed diagnosis in type I diabetes.
• Those engaging in high-risk behaviours were more likely to avoid HIV testing due to fear of a positive diagnosis, with worrying implications regarding onward transmission. Data from the Health Protection Agency indicates that 50% of new diagnoses are late in the UK.
• Broadly, late diagnosis affects vulnerable groups such as older people or those living in poverty.
• Patients delayed seeking help from clinicians for a number of conditions including chronic kidney disease, dementia, HIV, stroke, myocardial infarction, epilepsy and tuberculosis. Late presentation was linked to symptom misinterpretation and lack of knowledge.
• Inadequate knowledge and training of doctors were barriers to prompt diagnosis for chronic kidney disease, COPD, dementia and tuberculosis.
• Restricted access, insufficient consultation time and resource constraints hindered diagnosis.
• There was very little material about the cost implications of delayed diagnosis. WHAT ARE THE IMPLICATIONS?: The training of doctors in the early diagnosis of COPD, dementia and tuberculosis has improved detection. Media campaigns to alert the public to the symptoms of stroke, heart attack and psychosis have had mixed results. Overall, public recognition has increased, but this may not have contributed to shortening patient delay.
This study includes information from health care systems outside the UK. However, policy makers may find future reviews of UK primary research into the late diagnosis of these conditions useful to understand the nature of the problem in a UK context. HOW DID WE GET THESE RESULTS?: We examined evidence from 43 systematic reviews for: chronic kidney disease, dementia, depression, type I diabetes, epilepsy, HIV, myocardial infarction, psychosis, stroke and tuberculosis.
We found 606 UK primary studies on late diagnosis, of which 12 investigated COPD, 12 investigated tuberculosis and 4 investigated epilepsy. While there were systematic reviews to draw on for most conditions, this was not the case for COPD (no systematic reviews), tuberculosis (systematic reviews with limited relevance to UK healthcare system) and epilepsy (systematic reviews focused on over-diagnosis), and so we used evidence from the primary studies.
Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.
