Maureen Dubreuil

Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study

OBJECTIVE The objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population. METHODS We conducted a cohort study using an electronic medical records database representative of the UK general population (1986-2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline. RESULTS Cohorts included 4196 persons with PsA, 59 281 with psoriasis and 11 158 with RA, with mean follow-up times of 5.9, 5.8 and 5.5 years, respectively. Incidence rates for diabetes were 7.3, 6.4 and 6.3 cases per 1000 person-years among individuals with PsA, psoriasis and RA, respectively. Age- and sex-matched HRs for diabetes were 1.72 (95% CI 1.46, 2.02) in PsA, 1.39 (95% CI 1.32, 1.45) in psoriasis and 1.12 (95% CI 1.01, 1.25) in RA. After adjustment for BMI, smoking and alcohol, the HRs were attenuated substantially (1.43, 1.24 and 1.00, respectively). With further adjustment for baseline glucocorticoid use and co-morbidities, the HRs were 1.33 (1.09, 1.61) in PsA, 1.21 (1.15, 1.27) in psoriasis and 0.94 (0.84, 1.06) in RA. CONCLUSION This general population study suggests an increased incidence of diabetes in PsA and RA, which is substantially explained by obesity and lifestyle factors. These findings support the importance of managing such factors in PsA and RA patients.

The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study

Objectives To evaluate the risk of incident myocardial infarction (MI), stroke and peripheral vascular disease (PVD) in individuals with systemic sclerosis (SSc) in a general population context. Methods We conducted a cohort study using a UK primary care database containing records from 1986 to 2011. SSc diagnoses, outcomes and cardiovascular risk factors were identified from electronic medical records. We conducted two cohort analyses: (1) MI and stroke, and (2) PVD, excluding individuals with prevalent disease at baseline for each analysis. We estimated HRs comparing SSc with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. Results Among 865 individuals with SSc (85.8% women, mean age 58.7 years), the incidence rates (IRs) of MI and stroke were 4.4 and 4.8 per 1000 person-years (PY), versus 2.5 and 2.5 per 1000 PY in the comparison cohort. The corresponding adjusted HRs were 1.80 (95% CI 1.07 to 3.05) for MI and 2.61 (95% CI 1.54 to 4.44) for stroke. Among 858 individuals with SSc (85.3% female, mean age 58.9 years), the IR of PVD was 7.6 per 1000 PY versus 1.9 per 1000 PY in the comparison cohort, with an adjusted HR of 4.35 (95% CI 2.74 to 6.93). Conclusions These findings provide the first general population-based evidence that SSc is associated with an increased risk of developing MI, stroke and PVD. Further insight into disease mechanisms, as well as how disease subtype, organ involvement and medication use may alter these increased risks, is needed.

Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study

Objective While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, the antioxidant effects of uric acid may have neuroprotective benefits. We evaluated the potential impact of incident gout on the risk of developing Alzheimers disease (AD) in a general population context. Methods We conducted an age-matched, sex-matched, entry-time-matched and body mass index (BMI)-matched cohort study using data from The Health Improvement Network, an electronic medical record database representative of the UK general population, from 1 January 1995 to 31 December 2013. Up to five non-gout individuals were matched to each case of incident gout by age, sex, year of enrolment and BMI. We compared incidence rates of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline. Multivariate hazard ratios (HRs) were calculated, while adjusting for smoking, alcohol use, physician visits, social deprivation index, comorbidities and medication use. We repeated the same analysis among patients with incident osteoarthritis (OA) as a negative control exposure. Results We identified 309 new cases of AD among 59 224 patients with gout (29% female, mean age 65 years) and 1942 cases among 238 805 in the comparison cohort over a 5-year median follow up (1.0 vs 1.5 per 1000 person-years, respectively). Univariate (age-matched, sex-matched, entry-time-matched and BMI-matched) and multivariate HRs for AD among patients with gout were 0.71 (95% CI 0.62 to 0.80) and 0.76 (95% CI 0.66 to 0.87), respectively. The inverse association persisted among subgroups stratified by sex, age group (<75 and ≥75 years), social deprivation index and history of CV disease. The association between incident OA and the risk of incident AD was null. Conclusions These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, supporting the purported potential neuroprotective role of uric acid.

Allopurinol initiation and all-cause mortality in the general population

Background Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population. Methods We conducted an incident user cohort study with propensity score matching using a UK general population database. The study population included individuals aged ≥40 years who had a record of hyperuricaemia (serum urate level >357 μmol/L for women and >416 μmol/L for men) between January 2000 and May 2010. To closely account for potential confounders of allopurinol use and risk of death, we constructed propensity score matched cohorts of allopurinol initiators and comparators (non-initiators) within 6-month cohort accrual blocks. Results Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92). Conclusions In this general population study, allopurinol initiation was associated with a modestly reduced risk of death in patients with hyperuricaemia and patients with gout. The overall benefit of allopurinol on survival may outweigh the impact of rare serious adverse effects.

Improved survival in rheumatoid arthritis: a general population-based cohort study.

Objective Mortality trends of rheumatoid arthritis (RA) are largely unknown over the past decade when new drugs and management strategies have been adopted to effectively treat RA. Methods Using The Health Improvement Network, an electronic medical record database representative of the UK general population, we identified patients with incident RA and up to five individuals without RA matched for age, sex and year of diagnosis between 1999 and 2014. The RA cohort was divided in two sub-cohorts based on the year of RA diagnosis: the early cohort (1999–2006) and the late cohort (2007–2014). We compared mortality rates, HRs (using a Cox proportional hazard model) and rate differences (using an additive hazard model) between RA and non-RA cohorts adjusting for potential confounders. Results Patients with RA diagnosed between 1999 and 2006 had a considerably higher mortality rate than their comparison cohort (ie, 29.1 vs 18.0 deaths/1000 person-years), as compared with a moderate difference in patients with RA diagnosed between 2007 and 2014 and their comparison cohort (17.0 vs 12.9 deaths/1000 years). The corresponding absolute mortality rate differences were 9.5 deaths/1000 person-years (95% CIs 7.5 to 11.6) and 3.1 deaths/1000 person-years (95% CI 1.5 to 4.6) and the mortality HRs were 1.56 (95% CI 1.44 to 1.69) and 1.29 (95% CI 1.17 to 1.42), respectively (both p values for interaction <0.01). Conclusion This general population-based cohort study indicates that the survival of patients with RA has improved over the past decade to a greater degree than in the general population. Improved management of RA and its associated comorbidities over recent years may be providing a survival benefit.

Ultrasound assessment of subcutaneous compressibility: a potential adjunctive diagnostic tool in eosinophilic fasciitis.

BackgroundEosinophilic fasciitis (EF) is an autoimmune, fibrotic disorder described initially with scleroderma-like skin changes where deep soft tissue sampling that includes fascia is frequently felt to be necessary to confirm the diagnosis. ObjectiveThe objective of this study was to distinguish forearm involvement by EF from other fibrosing diseases and from control subjects with normal skin and fascia using B-mode ultrasound. MethodsA cross-sectional study over a 4-year period in which clinically involved forearm skin of consecutive patients with EF (n = 12), diabetic cheiroarthropathy (n = 8), diffuse systemic sclerosis (n = 23), and control subjects (n = 8) was evaluated by 12-MHz, B-mode ultrasound for degree of subcutaneous tissue compressibility, and this finding was compared with the criterion standard of clinical diagnostic criteria for each disease process. ResultsSubcutaneous compressibility in EF was significantly reduced when compared with diffuse systemic sclerosis and with control subjects. Subcutaneous thinning was observed in some patients with EF (4/12), diabetic cheiroarthropathy (4/8), and diffuse systemic sclerosis (6/23), but not in control subjects. Diabetic cheiroarthropathy and diffuse systemic sclerosis patients with subcutaneous thinning had less than 20% subcutaneous compressibility, whereas only 1 of 12 EF patients had compressibility of more than 20% regardless of subcutaneous thinning. ConclusionsA 12-MHz, B-mode ultrasound may be used to measure subcutaneous compressibility, thereby serving as an adjunct tool in distinguishing EF from diffuse systemic sclerosis, especially when tissue sampling is less feasible or when the result of tissue sampling is equivocal.

The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States

OBJECTIVE Positive HLA-B*5801 carriers are at greater risk of experiencing rare but severe allopurinol hypersensitivity syndrome (AHS) [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)]; however, HLA-B*5801 prevalence and AHS risk vary by race/ethnicity. We evaluated the cost-effectiveness of HLA-B*5801 testing according to race/ethnicity in the United States. METHODS We determined the cost-effectiveness of universal testing for HLA-B*5801 compared to no testing prior to the initiation of allopurinol per US major race/ethnicity groups. Using US-specific data, SJS/TEN risks and HLA-B*5801 prevalences were modeled per race/ethnicity (i.e., 1/3846 and 0.7% among Caucasians and Hispanics, 1/735 and 3.8% among African Americans, and 1/336 and 7.4% among Asians, respectively). Those who tested positive for HLA-B*5801 received febuxostat. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime. RESULTS Compared to no testing, universal testing for HLA-B*5801 costs more and was more effective for all races/ethnicities. The ICERs varied substantially across racial/ethnic groups, following their HLA-B*5801 prevalences. HLA-B*5801 testing was cost-effective for African Americans (ICER

Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study

83,450) and Asians (ICER

Trends in Emergency Department Visits and Charges for Gout in the United States between 2006 and 2012

64,190), but not for Caucasians or Hispanics (ICER

Validity of ankylosing spondylitis diagnoses in The Health Improvement Network.

183,720), using accepted US willingness-to-pay threshold (