Scientific
publications

At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Miami, Florida, USA, a trainees symposium was held. Rheumatology and dermatology trainees, engaged in psoriasis or psoriatic arthritis research, presented their work. This report briefly reviews 6 oral presentations and 21 posters presented at that meeting.

Over the last two decades, the use of ADHD medication in US youth has markedly increased. However, less is known about ADHD medication use among European children and adolescents. A repeated cross-sectional design was applied to national or regional data extracts from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The prevalence of ADHD medication use was assessed, stratified by age and sex. Furthermore, the most commonly prescribed ADHD medications were assessed. ADHD medication use prevalence increased from 1.8% to 3.9% in the Netherlands cohort (relative increase: +111.9%), from 3.3% to 3.7% in the US cohort (+10.7%), from 1.3% to 2.2% in the German cohort (+62.4%), from 0.4% to 1.5% in the Danish cohort (+302.7%), and from 0.3% to 0.5% in the UK cohort (+56.6%). ADHD medication use was highest in 10-14-year olds, peaking in the Netherlands (7.1%) and the US (8.8%). Methylphenidate use predominated in Europe, whereas in the US amphetamines were nearly as common as methylphenidate. Although there was a substantially greater use of ADHD medications in the US cohort, there was a relatively greater increase in ADHD medication use in youth in the four European countries. ADHD medication use patterns in the US differed markedly from those in western European countries.

OBJECTIVE: To determine the risk of fracture and osteoporosis among patients with psoriatic arthritis (PsA) and psoriasis, compared with the general population and patients with rheumatoid arthritis (RA). METHODS: A population-based cohort study was performed in The Health Improvement Network in the UK using data from 1994 to 2014. Patients aged 18-89 years with PsA or psoriasis and up to five unexposed controls matched by practice and start date within that practice were included. Patients with RA and matched controls were included for comparison. Severe psoriasis was defined by a code for psoriasis and either phototherapy or a systemic medication for psoriasis. Incidence and adjusted HRs (aHR) for fracture (all, hip, vertebral) were calculated. RESULTS: Patients with PsA (n=9788), psoriasis (n=158 323) and controls (n=821 834) were identified. Patients with PsA had an elevated risk of all fracture aHR 1.26 (1.06 to 1.27). Patients with mild psoriasis had elevated risk of all fractures, vertebral and hip fracture: aHR 1.07 (1.05 to 1.10), 1.17 (1.03 to 1.33) and 1.13 (1.04 to 1.22). Patients with severe psoriasis had significantly elevated risk of all fracture and vertebral fracture: aHR 1.26 (1.15 to 1.39) and 2.23 (1.54 to 3.22). CONCLUSIONS: PsA and psoriasis are associated with an elevated risk for fracture.

Overexpression of VEGF is implicated in the pathogenesis of both renal cell carcinoma (RCC) and age-related macular degeneration (AMD). We evaluated the association between AMD and RCC risk. We conducted a matched case-control study within a population-representative database from the United Kingdom. Study cases were defined as individuals with any diagnostic code of RCC. For every case, four eligible controls were matched on age, sex, practice site, calendar time, and duration of follow-up. Exposure of interest was diagnosis of AMD prior to cancer diagnosis. Adjusted ORs and 95% confidence intervals (CI) for RCC were estimated using conditional logistic regression. In a secondary analysis, we evaluated the association between other retinopathies and RCC and AMD and the hypovascular pancreatic cancer. The study population included 1,547 patients with RCC and 6,066 matched controls. Median follow-up time was 6 years (IQR, 3-9). AMD diagnosis was associated with a significantly increased RCC risk (OR, 1.89; 95% CI, 1.09-3.29). In contrast, there was no association between other retinopathies and RCC risk (OR, 0.8; 95% CI, 0.56-1.15). AMD was associated with a lower risk for pancreatic cancer (OR, 0.47; 95% CI, 0.35-0.64). Patients with AMD may be at higher risk for RCC. Providers should be aware of this potential link and consider screening for RCC within this population. Providers should be aware of the potential link between AMD and RCC. .

OBJECTIVE: To assess clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2) compared with a two-layer compression system (TLCS; KTwo) and a four-layer compression system (FLCS; Profore) in treating newly-diagnosed venous leg ulcers (VLUs) in clinical practice in the UK, from the perspective of the NHS. METHOD: This was a retrospective cohort analysis of the case records of patients with newly-diagnosed VLUs randomly extracted from The Health Improvement Network (THIN) database (a nationally representative database of clinical practice among patients registered with general practitioners in the UK) who were treated with either TLCCB (n=200), TLCS (n=200) or FLCS (n=200). The clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over six months after starting treatment. RESULTS: Patients' mean age was 72 years and 58% were female. Time from wound onset to the start of compression was a mean of two months, and when starting compression the wound size was a mean of 45 cm . The distribution of healing was significantly different between the three groups; 76% of wounds in the TLCCB group healed by six months compared with 70% and 64% in the TLCS and FLCS groups, respectively (p=0.006). Time to healing was significantly less in the TLCCB group compared with the two other groups (p=0.003). Patients in the TLCCB group experienced better health-related quality of life over six months (0.413 quality-adjusted life years (QALYs) per patient), compared with the TLCS and FLCS groups (0.404 and 0.396 QALYs per patient, respectively). The mean six-month NHS management cost was £3045, £3842 and £4480 per patient in the TLCCB, TLCS and FLCS groups, respectively. CONCLUSION: Real-world evidence demonstrates that treating newly-diagnosed VLUs with TLCCB, compared with the other two compression systems, affords a more cost-effective use of NHS-funded resources in clinical practice since it resulted in an increased healing rate, better health-related quality of life and a reduction in NHS management cost.

BACKGROUND: An association between AS03 adjuvanted pandemic influenza vaccine and the occurrence of Bell's palsy was found in a population based cohort study in Stockholm, Sweden. To evaluate this association in a different population, we conducted a self-controlled case series in a primary health care database, THIN, in the United Kingdom. The aim of this study was to determine whether there was an increased risk of Bell's palsy following vaccination with any influenza vaccine containing A/California/7/2009 (H1N1)-like viral strains. Secondly, we investigated whether risks were different following pandemic influenza A(H1N1)pdm09 vaccines and seasonal influenza vaccines containing the influenza A(H1N1)pdm09 strain. METHODS: The study population comprised all incident Bell's palsy cases between 1 June 2009 and 30 June 2013 identified in THIN. We determined the relative incidence (RI) of Bell's palsy during the 6 weeks following vaccination with either pandemic or seasonal influenza vaccine. All analyses were adjusted for seasonality and confounding variables. RESULTS: We found an incidence rate of Bell's palsy of 38.7 per 100,000 person years. Both acute respiratory infection (ARI) consultations and pregnancy were found to be confounders. When adjusted for seasonality, ARI consultations and pregnancies, the RI during the 42 days after vaccination with an influenza vaccine was 0.85 (95% CI: 0.72-1.01). The RI was similar during the 42 days following seasonal vaccine (0.96, 95%CI: 0.82-1.13) or pandemic vaccine (0.73, 95%CI: 0.47-1.12). CONCLUSION: We found no evidence for an increased incidence of Bell's palsy following seasonal influenza vaccination overall, nor for monovalent pandemic influenza vaccine in 2009.

IMPORTANCE: A bidirectional relationship exists between epilepsy and depression. However, any putative biological gradient between depression severity and the risk of epilepsy, and the degree to which depression mediates the influence of independent risk factors for epilepsy, has yet to be examined. OBJECTIVE: To determine the effect of depression on the risk of epilepsy and seizure outcomes. DESIGN, SETTING, AND PARTICIPANTS: An observational study of a population-based primary care cohort (all patients free of prevalent depression and epilepsy at 18-90 years of age who were active after the Acceptable Mortality Reporting date in The Health Improvement Network database) and a prospectively collected tertiary care cohort (all patients whose data were prospectively collected from the Calgary Comprehensive Epilepsy Programme). The analyses were performed on March 16, 2016. MAIN OUTCOME AND MEASURES: The hazard of developing epilepsy after incident depression and vice versa was calculated. In addition, a mediation analysis of the effect of depression on risk factors for epilepsy and the odds of seizure freedom stratified by the presence of depression were performed. RESULTS: We identified 10 595 709 patients in The Health Improvement Network of whom 229 164 (2.2%) developed depression and 97 177 (0.9%) developed epilepsy. The median age was 44 years (interquartile range, 32-58 years) for those with depression and 56 years (interquartile range, 43-71 years) for those with epilepsy. Significantly more patients with depression (144 373 [63%] were women, and 84 791 [37%] were men; P < .001) or epilepsy (54 419 [56%] were women, and 42 758 [44%] were men; P < .001) were female. Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04 [95% CI, 1.97-2.09]; P < .001), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55 [95% CI, 2.49-2.60]; P < .001) There was an incremental hazard according to depression treatment type with lowest risk for those receiving counselling alone (HR, 1.84 [95% CI, 1.30-2.59]; P < .001), an intermediate risk for those receiving antidepressants alone (HR, 3.43 [95% CI, 3.37-3.47]; P < .001), and the highest risk for those receiving both (HR, 9.85 [95% CI, 5.74-16.90]; P < .001). Furthermore, depression mediated the relationship between sex, social deprivation, and Charlson Comorbidity Index with incident epilepsy, accounting for 4.6%, 7.1%, and 20.6% of the total effects of these explanatory variables, respectively. In the Comprehensive Epilepsy Programme, the odds of failing to achieve 1-year seizure freedom were significantly higher for those with depression or treated depression. CONCLUSIONS AND RELEVANCE: Common underlying pathophysiological mechanisms may explain the risk of developing epilepsy following incident depression. Treated depression is associated with worse epilepsy outcomes, suggesting that this may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy.

This cohort study uses UK primary care database data to explore the association between long-term quinine exposure and all-cause mortality.

Though previous studies have demonstrated an increased fracture risk in females with anorexia nervosa (AN), fracture risk in males is not well characterized. The objective of this study was to examine sex differences in fracture risk and site-specific fracture incidence in AN. We performed a population-based retrospective cohort study using The Health Improvement Network (THIN; a large database of anonymized electronic medical records collected at primary care clinics throughout the United Kingdom). The median calendar year for the start of the observation period was 2004-2005. We identified 9239 females and 556 males <60 years of age with AN, and 97,889 randomly selected sex-, age-, and practice-matched participants without eating disorders (92,329 females and 5560 males). Multivariable Cox regression was used to estimate the hazard ratio (HR) for incident fracture. Median age at start of observation was 29.8 years in females and 30.2 years in males. The HR for fracture associated with AN differed by sex and age (interaction p = 0.002). Females with AN had an increased fracture risk at all ages (HR, 1.59; 95% confidence interval [CI], 1.45 to 1.75). AN was associated with a higher risk of fracture among males >40 years of age (HR, 2.54; 95% CI, 1.32 to 4.90; p = 0.005) but not among males ≤40 years. Females with AN had a higher risk of fracture at nearly all anatomic sites. The greatest excess fracture risk was noted at the hip/femur (HR, 5.59; 95% CI, 3.44 to 9.09) and pelvis (HR, 4.54; 95% CI, 2.42 to 8.50) in females and at the vertebrae (HR, 7.25; 95% CI, 1.21 to 43.45) for males with AN. AN was associated with higher incident fracture risk in females across all age groups and in males >40 years old. Sites of highest fracture risk include the hip/femur and pelvis in females and vertebrae in males with AN. © 2016 American Society for Bone and Mineral Research.

CONTEXT: Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. OBJECTIVES: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. DESIGN: General practice, population-based, retrospective cohort study (January 2013 to September 2015). SETTING: The Health Improvement Network database. PARTICIPANTS: A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. RESULTS: Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). CONCLUSIONS: Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.