Objective.: Lowering serum uric acid (SUA) levels can essentially cure gout; however, this is not widely practiced. To summarize epidemiologic evidence related to this causal link, we conducted a systematic review of the published literature reporting the association between SUA level and incident and recurrent gout (i.e., gout flares).Methods.: We systematically searched Medline, EMBASE, and the Cochrane Database of Systematic Reviews using separate search strategies for incident gout and recurrent gout. We screened 646 abstracts to identify 8 eligible articles reporting gout incidence and 913 abstracts to identify 18 articles reporting recurrent gout.Results.: For both gout incidence and recurrence, a graded trend was observed where the risk was increased with higher SUA levels. Gout incidence rates per 1000 person-years from population-based studies ranged from 0.8 (SUA ≤ 6 mg/dl) to 70.2 cases (SUA ≥ 10 mg/dl). Recurrent gout risk in clinical cohorts ranged from 12% (SUA ≤ 6 mg/dl) to 61% (SUA ≥ 9 mg/dl) among those receiving urate-lowering therapy (ULT), and 3.7% (SUA 6–7 mg/dl) to 61% (SUA > 9.3 mg/dl) after successful ULT. Retrospective database studies also showed a graded relationship, although the strength of the association was weaker. Studies reporting mean flares or time-to-flare according to SUA showed similar findings.Conclusion.: This systematic review confirms that higher SUA levels are associated with increased risk of incident and recurrent gout in a graded manner. Although few prospective cohorts have evaluated incident and recurrent gout according to SUA, the existing evidence underscores the need to treat to SUA targets, as recommended by the American College of Rheumatology and the European League Against Rheumatism.

Observational burden of illness studies are used in pharmacoepidemiology to address a variety of objectives, including contextualizing the current treatment setting, identifying important treatment gaps, and providing estimates to parameterize economic models. Methodologies such as retrospective chart review may be utilized in settings for which existing datasets are not available or do not include sufficient clinical detail. While specifying the number of charts to be extracted and/or determining whether the number that can feasibly extracted will be clinically meaningful is an important study design consideration, there is a lack of rigorous methods available for sample size calculation in this setting. The objective of this study was to develop recommended sample size calculations for use in such studies. Calculations for identifying the optimal feasible sample size calculations were derived, for studies characterizing treatment patterns and medical costs, based on the ability to comprehensively observe treatments and maximize precision of resulting 95% confidence intervals. For cost outcomes, if the standard deviation is not known, the coefficient of variation cv can be used as an alternative. A case study of a chart review of advanced melanoma (MELODY) was used to characterize plausible values for cv in a real-world example. Across sample sizes, any treatment given with greater than 1% frequency has a high likelihood of being observed. For a sample of size 200, and a treatment given to 5% of the population, the precision of a 95% confidence interval (CI) is expected to be ±0.03. For cost outcomes, for the median cv value observed in the MELODY study (0.72), a sample size of approximately 200 would be required to generate a 95% CI precise to within ±10% of the mean. This study presents a formal guidance on sample size calculations for retrospective burden of illness studies. The approach presented here is methodologically rigorous and designed for practical application in real-world retrospective chart review studies.

Background: Duchenne muscular dystrophy (DMD) is a severe rare progressive inherited neuromuscular disorder, leading to loss of ambulation (LOA) and premature mortality. The standard of care for patients with DMD has been treatment with corticosteroids for the past decade; however a synthesis of contemporary data describing the clinical course of DMD is lacking. The objective was to summarize age at key clinical milestones (loss of ambulation, scoliosis, ventilation, cardiomyopathy, and mortality) in the corticosteroid-treatment-era.Methods: A systematic review was conducted using MEDLINE and EMBASE. The percentage experiencing key clinical milestones, and the mean or median age at those milestones, was synthesized from studies from North American populations, published between 2007 and 2018.Results: From 5637 abstracts, 29 studies were included. Estimates of the percentage experiencing key clinical milestones, and age at those milestones, showed heterogeneity. Up to 30% of patients lost ambulation by age 10 years, and up to 90% by 15 years of age. The mean age at scoliosis onset was approximately 14 years. Ventilatory support began from 15 to 18 years, and up to half of patients required ventilation by 20 years of age. Registry-based estimates suggest that 70% had evidence of cardiomyopathy by 15 years and almost all by 20 years of age. Finally, mortality rates up to 16% by age 20 years were reported; among those surviving to adulthood mortality was up to 60% by age 30 years.Conclusions: Contemporary natural history studies from North America report that LOA on average occurs in the early teens, need for ventilation and cardiomyopathy in the late teens, and death in the third or fourth decade of life. Variability in rates may be due to differences in study design, treatment with corticosteroids or other disease-modifying agents, variations in clinical practices, and dystrophin mutations. Despite challenges in synthesizing estimates, these findings help characterize disease progression among contemporary North American DMD patients.

BACKGROUND: Heart failure (HF) affects approximately 6 million Americans, with prevalence projected to increase by 46% and direct medical costs to reach $53 billion by 2030. Hospitalizations are th...

Objective To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB). Design A retrospective claims-based study (2007–2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison. Setting United States, commercially and Medicare-insured population. Participants 154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women. Main outcome measures Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index (‘at baseline’) and every 6 months post index. Burden was categorised as no burden (0), low burden (1–89), medium burden (90–499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model. Results Median (IQR) baseline anticholinergic burden was 30 (0.0–314.0) and higher among older (≥65 years, 183 [3.0–713.0]) versus younger (<65 years, 13 [0.0–200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0–3.2) for those with no burden, to 7.4 (95% CI 7.1–7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without). Conclusion Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.