Ashley Bonner

Differences in clinical manifestations between childhood-onset lupus and adult-onset lupus: a meta-analysis:

Objective: It is known that age at disease onset has an impact on the clinical course andoutcome of systemic lupus erythematosus (SLE); however, the precise differences in theprevalence of SLE manifestations are debated. Our objective was to conduct a systematicliterature review and meta-analysis of all studies that directly compare childhood-onset lupus with adult-onsetlupus to determine which clinical manifestations vary with age at disease onset. Methods: A comprehensive literature search of the MEDLINE/PubMed,EMBASE, CINAHL, and SCOPUS databases was conducted to identify relevant articles. Study quality was assessed using the STROBE checklist. Study sample characteristics and clinical manifestation event rates were extracted from each study. Pooled odds ratios (ORs) were calculated using the random effects method, and between-study heterogeneity was quantified using the I2 statistic. Results: Of the 484studies identified by the search strategy, 16 were included in this review. The total number of patients was 5993 adults and 905 children with SLE. Study quality was on average 16/32, ranging from 8 to 29. Several statistically significant differences were found: malar rash, ulcers/mucocutaneous involvement, renal involvement, proteinuria, urinary cellular casts, seizures, thrombocytopenia, hemolytic anemia, fever, and lymphadenopathy were more common in childhood-onset SLE with ORs ranging from 1.3 to 3.7; however, Raynauds, pleuritis, and sicca were more common in adult-onset SLE (twice as common). Conclusions: The results of this meta-analysis suggest that some clinical manifestations of lupus are different in childhood-onset SLE and adult-onset SLE.

Association of C-reactive protein with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group.

This study was performed to determine the prevalence of elevated C‐reactive protein (CRP) levels and the significance of CRP in clinical parameters in systemic sclerosis (SSc; scleroderma) patients.

Network meta-analysis using R: a review of currently available automated packages.

Network meta-analysis (NMA) – a statistical technique that allows comparison of multiple treatments in the same meta-analysis simultaneously – has become increasingly popular in the medical literature in recent years. The statistical methodology underpinning this technique and software tools for implementing the methods are evolving. Both commercial and freely available statistical software packages have been developed to facilitate the statistical computations using NMA with varying degrees of functionality and ease of use. This paper aims to introduce the reader to three R packages, namely, gemtc, pcnetmeta, and netmeta, which are freely available software tools implemented in R. Each automates the process of performing NMA so that users can perform the analysis with minimal computational effort. We present, compare and contrast the availability and functionality of different important features of NMA in these three packages so that clinical investigators and researchers can determine which R packages to implement depending on their analysis needs. Four summary tables detailing (i) data input and network plotting, (ii) modeling options, (iii) assumption checking and diagnostic testing, and (iv) inference and reporting tools, are provided, along with an analysis of a previously published dataset to illustrate the outputs available from each package. We demonstrate that each of the three packages provides a useful set of tools, and combined provide users with nearly all functionality that might be desired when conducting a NMA.

Comparison of Anti-TNF Treatment Initiation in Rheumatoid Arthritis Databases Demonstrates Wide Country Variability in Patient Parameters at Initiation of Anti-TNF Therapy

OBJECTIVE Characteristics of Canadian RA patients started on anti-tumor necrosis factor (TNF) treatment were compared with 12 other countries. METHODS Data from the Optimization of HUMIRA trial (OH) were compared with Canadian real world studies [Ontario Biologics Research Initiative (OBRI) and the Real-Life Evaluation of Rheumatoid Arthritis in Canadians Receiving HUMIRA (REACH)], and to data from American, Australian, British, Czech, Danish, Dutch, Finnish, German, Italian, Norwegian, Spanish, and Swedish RA databases. Patient characteristics and temporal trends at initiation of anti-TNF therapy were compared between countries. RESULTS Baseline Disease Activity Scores (DAS28) varied from 5.3 to 6.6. Lower disease severity was noted in databases from countries with less restrictive anti-TNF coverage: Dutch [based on previous disease-modifying antirheumatic drugs (DMARD) use, DAS28, swollen joint count (SJC), tender joint count (TJC), Health Assessment Questionnaire Disability Index (HAQ-DI), Danish (previous DMARD use, DAS28), Norwegian (DAS28, SJC, TJC, visual analog scale (VAS) of global health), and Swedish (DAS28, SJC, TJC, HAQ-DI)]. RA databases showed lower disease scores than did OH (P < 0.05). The US databases also showed lower disease severity (CORRONA: previous DMARD use, SJC, TJC; National Data Bank for Rheumatic Diseases: HAQ, P < 0.001). The UK and Czech Republic had restrictive coverage and higher mean baseline DAS28 than OH (P < 0.001). Baseline DAS28 in the registries with published data lowered over time (British, Norwegian, Danish, and Swedish) but less for the British (P < 0.001). CONCLUSIONS These results confirm that regional variation exists between the 13 countries analyzed in the initiation of treatment with anti-TNF agents among RA patients and suggest that in some cases this variation may be increasing. In some countries the mean baseline disease severity declined over time and regional reimbursement policies and differences in physician preferences may be influencing initiation of anti-TNF therapy in RA.

Differences in Autoantibody Profiles and Disease Activity and Damage Scores Between Childhood- and Adult-Onset Systemic Lupus Erythematosus: A Meta-Analysis

BACKGROUND Age at systemic lupus erythematosus (SLE) onset may impact autoantibodies, disease activity, and damage. A meta-analysis of all studies that directly compared childhood-onset lupus (cSLE) to adult-onset lupus was performed to determine which autoantibodies and whether activity and damage scores vary between adult- and pediatric-onset SLE. METHODS A literature search of the MEDLINE/PubMed, EMBASE, CINAHL, and SCOPUS databases (until January 2011) was conducted to identify relevant articles. Study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two independent reviewers determined eligibility criteria. Pooled odds ratios and mean differences were calculated assuming random effects, and heterogeneity was estimated and presented as (odds ratios; 95% confidence interval). RESULTS Of the 484 studies identified, 19 were eligible. The total number of patients was 7519. Mean trial quality was 18/32, ranging from 8 to 29. Several statistically significant differences were found: more frequently positive anti-dsDNA antibody (1.97; 1.31 to 2.96) and IgG/IgM anticardiolipin antibody (1.66; 1.20 to 2.28), and mean disease activity scores (SLE Disease Activity Index) (4.73; 2.13 to 7.32) were higher in cSLE. Disease damage [SLE damage index (SDI)] was lower in cSLE, but not significantly (0.50; -0.13 to 1.14). Rheumatoid factor was increased in adults (0.53; 0.32 to 0.87). The frequency of the autoantibodies and laboratories was not different between the groups (ANA, anti-Smith, anti-RNP, anti-U1RNP, anti-Ro and anti-La, antiphospholipid, lupus anticoagulant, complements, ssDNA, and Coombs test). CONCLUSIONS The results of this meta-analysis suggest that cSLE may have different autoantibody profiles (increased anti-dsDNA and anticardiolipin antibody, less rheumatoid factor), and more disease activity than adult-onset SLE. Damage may be less in children, but larger studies are needed.

Association of Gastroesophageal Factors and Worsening of Forced Vital Capacity in Systemic Sclerosis

Objective. Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc) and causes death. Once lung fibrosis occurs, disease course may become stable or decline. Little is known about risks for progression. We studied SSc–gastroesophageal (GE) involvement in relation to worsening forced vital capacity (FVC) on pulmonary function tests (PFT) to investigate whether it was related to progression. Our objective was to determine whether GE reflux and dysphagia are associated with progressive moderate/severe ILD as measured by PFT over 3 years. Methods. The Canadian Scleroderma Research Group is a multicenter SSc database that collects data annually. Using indicators of GE involvement and annual PFT, comparisons were made between no/mild ILD, stable moderate/severe ILD, and progressive moderate/severe ILD groups based on changes of FVC. Multivariate analyses determined associations between GE factors and ILD development and progression. Results. There were 1043 patients with SSc (mean age 55.7 yrs, mean disease duration 10.8 yrs); one-quarter had pulmonary fibrosis on chest radiograph that was related to FVC percentage predicted (Spearman’s rho −0.39; p < 0.01). Physician indicators such as esophageal dysmotility (p = 0.009) and postesophageal dilatation (p = 0.041), and patient indicators such as difficulty swallowing (p = 0.016) and waking up choking (p = 0.026) were associated with low FVC. In comparing progressive and stable moderate/severe FVC (< 70% predicted), early satiety (p = 0.018) and a combination term of postdilatation and choking (p = 0.042) increased risk of progression of ILD. Topoisomerase I was not associated with progression over followup. Conclusion. Symptoms of esophageal dysmotility were associated with worsening FVC in SSc, especially if both need for esophageal dilatation and choking were present.

Myopathy is a poor prognostic feature in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG) cohort

Objective: To determine the clinical impact of muscle involvement in a large systemic sclerosis (SSc) cohort. Method: Using the Canadian Scleroderma Research Group (CSRG) database, SSc patients with either elevated creatine kinase (CK) or a prior history of myositis/myopathy were identified. Regression and Kaplan–Meier analyses were performed to determine characteristics associated with muscle involvement in SSc and survival outcome. Results: In 1145 patients with SSc, 5.6% had an elevated CK. This subset was more likely to be male (24.5% in elevated CK vs. 12.6% in normal CK, p < 0.013), younger (52 vs. 56 years, p < 0.045), have diffuse cutaneous SSc (dcSSc; 40.4% vs. 37.9%, p < 0.002), tendon friction rubs (30.0% vs. 13.4%, p < 0.001), and forced vital capacity (FVC) < 70% (23.9% vs. 13.1%, p < 0.039), be ribonucleoprotein (RNP) antibody positive (12.0% vs. 5.0%, p < 0.032), topoisomerase1 (topo1)-antibody positive (26.0% vs. 14.4%, p < 0.026), have a higher modified Rodnan skin score (MRSS; 16.14 vs. 9.81, p < 0.001), and a higher Health Assessment Questionnaire (HAQ) score (0.98 vs. 0.79, p < 0.011). Survival was reduced for patients with elevated CK (p < 0.025). Nearly 10% of patients in the CSRG cohort had a prior history of myositis/myopathy. This subset also had findings similar to those with elevated CK and increased mortality (p < 0.003). Conclusions: Muscle involvement in SSc has a poor prognosis impacting survival, especially in men with early dcSSc with topo1 and RNP autoantibodies and interstitial lung disease (ILD).

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

BackgroundOpioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence.Methods/DesignThe authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse).DiscussionUsing evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine.Systematic review registrationPROSPERO CRD42013006507.

Determining Best Practices in Early Rheumatoid Arthritis by Comparing Differences in Treatment at Sites in the Canadian Early Arthritis Cohort

Objective. To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort. Methods. Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies. Results. The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (−1.82 and −2.09, respectively, at 6 mos, and −2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at the last followup, sites B and H had the most in remission. Subcutaneous methotrexate was used more overall and earlier at sites B and H. Those sites used less steroid therapy, and site B had the second-highest use of triple disease-modifying antirheumatic drugs at any visit. Medications were increased more in 2 of the 3 smallest sites. Biologics were used by 9 months most in the smallest (50.0%) and then largest (19.6%) sites. Conclusion. Sites in an early inflammatory arthritis cohort yielded different outcomes. Better outcomes up to 12 months may result from initial treatment with early combination therapy and/or subcutaneous methotrexate.

Agreement with Guidelines from a Large Database for Management of Systemic Sclerosis: Results from the Canadian Scleroderma Research Group

Objective. We determined congruence with published guidelines from the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trials and Research group, for systemic sclerosis (SSc) investigations and treatment practices within the Canadian Scleroderma Research Group (CSRG). Methods. Investigations and medication use for SSc complications were obtained from records of patients with SSc in the CSRG to determine adherence to guidelines for patients enrolled before and after the guidelines were published. Results. The CSRG database of 1253 patients had 992 patients with SSc enrolled before publication of the guidelines and 261 after. For pulmonary arterial hypertension (PAH) treatment, there were no differences in use before and after the guidelines, yet annual echocardiograms for PAH screening were done in 95% of patients enrolled before the guidelines and in only 86% of those enrolled after (p <0.0001), and fewer followup echocardiograms were done 1 year later in the latter group (88% vs 59%). No differences were found for the frequency of PAH-specific treatment; 60% had ever used calcium channel blockers for Raynaud’s phenomenon, with no differences in the groups before and after the guidelines. But the use of phosphodiesterase type 5 inhibitors (which does not have guidelines) was increased in the after-guidelines group. Proton pump inhibitors were used in > 80% with gastroesophageal reflux disease before and after the guidelines. One-quarter with gastrointestinal symptoms were taking prokinetic drugs. For those with past SSc renal crisis, use of angiotensin-converting enzyme inhibitors was not different before and after the guidelines. For early diffuse SSc < 2 years, ever-use of methotrexate was similar (one-quarter of each group); and for symptomatic interstitial lung disease, 19% had ever used cyclophosphamide before the guidelines and 9% after (p = nonsignificant). CSRG practices were generally comparable to recently published guidelines; however, use of iloprost and bosentan was low for digital ulcers because these drugs are not approved for use in Canada. Conclusion. There did not seem to be an increase in adherence to recommendations once the guidelines were published. For many guidelines, 25% to 40% of patients who would qualify received the recommended treatment.