Gabriel Baron

Influence of replacing tuberculin skin test with ex vivo interferon γ release assays on decision to administer prophylactic antituberculosis antibiotics before anti-TNF therapy

Background The recommendations for detecting latent tuberculosis infection (LTBI) before antitumour necrosis factor (anti-TNF) therapy are based on the tuberculin skin test (TST), which lacks both specificity and sensitivity and can lead to unnecessary treatment with antibiotics. A study was undertaken to investigate the effect of replacing TST with interferon γ (IFNγ) release assays (IGRA) in screening for LTBI and deciding to begin prophylactic antituberculosis (TB) antibiotics before anti-TNF therapy in immune-mediated inflammatory diseases. Methods In 15 tertiary care hospitals, consecutive patients with rheumatoid arthritis, spondylarthropathies or Crohns disease were screened for LTBI before anti-TNF therapy with TST, QuantiFERON TB Gold in tube (QTF-Gold IT) and T-SPOT.TB at the same time. The potential diagnosis of LTBI and the effect on the decision to begin antibiotic prophylaxis were assessed. Results Among 429 patients, 392 had results for the three tests. The results for TST, T-SPOT.TB and QTF Gold IT were positive for 35.2%, 15.1% and 9.9% of patients, respectively (p<0.0001). Antibiotics were required for 177 patients (45.2%) if positive TST results were included in the LTBI definition, 107 patients (27.3%) if TST results were replaced with results from one of the IGRA tests and 84 patients (21.4%) if TST results were replaced with QTF-Gold IT results (p<0.0001). The decision on the use of antibiotic prophylaxis was changed for 113 patients (28.8%, 95% CI 24.4% to 33.6%) if TST results were replaced with QTF-Gold IT results. Conclusions Replacing TST with IGRA for determining LTBI allowed the proportion of patients with immune-mediated inflammatory diseases needing prophylactic anti-TB antibiotics before beginning anti-TNF agents to be reduced by half. TrialRegNo: NCT00811343.

Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial

Aim To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA). Methods We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40u2005mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6u2005months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection. Results 99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62u2005years, 85% were women, and mean level of pain was 62u2005mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups. Conclusions Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs. Trials registration number NCT00597623.

Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome ☆

BACKGROUNDnCardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.nnnMETHODSnInclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.nnnRESULTSn214 CHB were included: 202 detected in utero at a median term of 23 weeks gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.nnnCONCLUSIONnIn this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Influence of vertebral fracture assessment by dual-energy X-ray absorptiometry on decision-making in osteoporosis: a structured vignette survey

OBJECTIVEnVertebral fracture assessment (VFA) is a radiographic method using DXA to diagnose vertebral fractures, validated for reproducibility, sensitivity and specificity as compared with spine radiographs. This study was designed to assess the impact of VFA results on decision-marking in osteoporosis, using a clinical vignette-based approach.nnnMETHODSnTwenty-nine rheumatologists provided data on post-menopausal women consulting for BMD measurement: clinical risk factors for osteoporosis, clinical characteristics of patients, BMD, T-score and VFA images. Standardized clinical vignettes were generated from these patients, and each rheumatologist assessed five vignettes assigned at random, in two distinct steps: first step without and second step with VFA data. At each step, they had to answer questions about the prescription of radiographs and treatments, using a yes/no format.nnnRESULTSnA total of 117 vignettes were available [117 patients: mean age 65.1 (10.1) years, lumbar spine T-score: -1.64 (0.92)], 36.7% with a personal history of fracture. Rheumatologists intended to prescribe radiographs in 62.4 and 46.2% cases (P = 0.0206) before and after VFA results, respectively; a change occurred in 36.8% of patients, i.e. a de novo prescription of radiographs in 12 patients, and a deleted prescription in 31 patients. VFA data induced a therapeutic change for 30.8% of patients.nnnCONCLUSIONnThis study shows that VFA results influence patient management, both for radiographs and treatment prescriptions.

Development and validation of a questionnaire assessing fears and beliefs of patients with knee osteoarthritis: the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ).

Objective We aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA. Design We sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique. Results 137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend. Conclusions We propose an 11-item questionnaire assessing patients fears and beliefs concerning knee OA with good content and construct validity.

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors

In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one‐third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).

Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial

Objective To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Design Cohort embedded pragmatic randomized controlled trial. Setting Trials registered on ClinicalTrials.gov. Participants 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). Main outcome measures The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Results Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Conclusions Sending email reminders about the FDA’s legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months. Trial registration ClinicalTrials.gov NCT01658254.

A personalized physical therapy program or usual care for patients with systemic sclerosis: A randomized controlled trial

To compare a physical therapy program to usual care of systemic sclerosis (SSc) patients on disability.

Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy: A Randomized Trial

BackgroundnActive discopathy is associated with a specific phenotype of chronic low back pain (LBP). Local inflammation has a role in active discopathy-associated symptoms.nnnObjectivenTo assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in patients with chronic LBP with active discopathy.nnnDesignnProspective, parallel-group, double-blind, randomized, controlled study. (ClinicalTrials.gov: NCT00804531).nnnSettingn3 tertiary care centers in France.nnnPatientsn135 patients with chronic LBP with active discopathy on magnetic resonance imaging (MRI).nnnInterventionnA single GC IDI (25 mg prednisolone acetate) during discography (nxa0= 67) or discography alone (nxa0= 68).nnnMeasurementsnThe primary outcome was the percentage of patients with LBP intensity less than 40 on an 11-point numerical rating scale (0 [no pain] to 100 [maximum pain] in 10-point increments) in the previous 48 hours at 1 month after the intervention. The main secondary outcomes were LBP intensity and persistent active discopathy on MRI at 12 months and spine-specific limitations in activities, health-related quality of life, anxiety and depression, employment status, and use of analgesics and nonsteroidal anti-inflammatory drugs at 1 and 12 months.nnnResultsnAll randomly assigned patients were included in the primary efficacy analysis. At 1 month after the intervention, the percentage of responders (LBP intensity <40) was higher in the GC IDI group (36 of 65 [55.4%]) than the control group (21 of 63 [33.3%]) (absolute risk difference, 22.1 percentage points [95% CI, 5.5 to 38.7 percentage points]; Pxa0= 0.009). The groups did not differ in LBP intensity at 12 months and in most secondary outcomes at 1 and 12 months.nnnLimitationnTertiary care setting.nnnConclusionnIn chronic LBP associated with active discopathy, a single GC IDI reduces LBP at 1 month but not at 12 months.nnnPrimary Funding SourcenFrench Ministry of Health.

Elaboration and validation of a questionnaire assessing patient expectations about management of knee osteoarthritis by their physicians: the Knee Osteoarthritis Expectations Questionnaire

Objectives To develop a questionnaire assessing the expectations of patients regarding management of osteoarthritis (OA of the knee. Methods A detailed document reporting on a qualitative analysis of interviews of patients with knee OA was sent to experts and a Delphi procedure was adopted for item generation. Eighty physicians (64 general practitioners, 16 rheumatologists) recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. The reliability of the questionnaire was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and the Bland–Altman technique. Results Sixty items were extracted from analysis of the interview data. The experts needed three Delphi rounds to obtain consensus on a 33-item provisional questionnaire. The item reduction process resulted in an 18-item questionnaire. Exploratory factor analysis extracted three main factors: factor 1 represented expectations for education, factor 2 expectations for information on technical and human support, and factor 3 expectations for physician empathy. The Cronbach α coefficient was 0.91 (95% CI 0.89 to 0.92). Expected divergent validity was observed. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good with an ICC of 0.79, and Bland–Altman analysis did not reveal a systematic trend. Conclusions A new 18-item questionnaire assessing patient expectations of management of knee OA by their physicians is proposed. The questionnaire has good content and construct validity.