Florence Tubach

Excess adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetics consequences. Previous studies have suggested that obesity could negatively affect the response to anti-TNF-α agents, notably infliximab (IFX). We aimed to determine whether body mass index (BMI) is involved in the response to IFX in rheumatoid arthritis (RA). We retrospectively examined data for 76 RA patients receiving IFX. BMI was calculated before treatment, and change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender and swollen joint count was analysed at 6 months after treatment. The primary outcome was decrease in DAS28 ≥1.2. Secondary outcomes were good response and remission according to EULAR. At baseline, the median [interquartile range] BMI was 26.6 [22.6-30.6] kg/m2. The number of patients with normal weight, overweight and obesity was 25, 29 and 22. In multivariable analyses, IFX treated patients with lower BMI showed a more frequent DAS28 decrease ≥1.2 (25.5 [22.3-28.3] vs. 28.0 [23.2-32.5], p=0.02, odds ratio [OR] 0.88 [95% confidence interval 0.79-0.98]), EULAR good response (25.3 [21.9-27.5] vs. 27.5 [24.3-31.2], p=0.03, OR 0.87 [0.76-0.99]) and EULAR remission, although not significant (25.3 [21.9-26.4] vs. 27.5 [23.2-30.9], p=0.14, OR 0.88 [0.75-1.04]). Obesity may negatively influence the response to IFX in RA. These data could help physicians to choose biologic agents for obese RA patients.

There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT. This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the ‘early’ strategy, RRT is initiated immediately. In the ‘delayed’ strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH 5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all. The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT. ClinicalTrials.gov NCT01932190 .

Introduction: Whether the inflammatory biomarker procalcitonin provides prognostic information across clinical settings and different acute respiratory tract infections (ARIs) is poorly understood. In the present study, we investigated the prognostic value of admission procalcitonin levels to predict adverse clinical outcome in a large ARI population. Methods: We analysed data from 14 trials and 4,211 ARI patients to study associations of admission procalcitonin levels and setting specific treatment failure and mortality alone at 30 days. We used multivariable hierarchical logistic regression and conducted sensitivity analyses stratified by clinical settings and ARI diagnoses to assess the results’ consistency. Results: Overall, 864 patients (20.5%) experienced treatment failure and 252 (6.0%) died. The ability of procalcitonin to differentiate patients with from those without treatment failure was highest in the emergency department setting (treatment failure area under the curve (AUC): 0.64 (95% confidence interval (CI): 0.61, 0.67), adjusted odds ratio (OR): 1.85 (95% CI: 1.61, 2.12), P P P <0.001). In primary care and intensive care unit patients, no significant association of initial procalcitonin levels and outcome was found. Conclusions: Admission procalcitonin levels are associated with setting specific treatment failure and provide the most prognostic information regarding ARI in the emergency department setting.

Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336 ), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk. CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems. ClinicalTrials.gov Identifier: NCT00882336

Case-only designs have been used since late 1980’s. In these, as opposed to case-control or cohort studies for instance, only cases are required and are self-controlled, eliminating selection biases and confounding related to control subjects, and time-invariant characteristics. The objectives of this systematic review were to analyze how the two main case-only designs – case-crossover (CC) and self-controlled case series (SCCS) – have been applied and reported in pharmacoepidemiology literature, in terms of applicability assumptions and specificities of these designs. We systematically selected all reports in this field involving case-only designs from MEDLINE and EMBASE up to September 15, 2010. Data were extracted using a standardized form. The analysis included 93 reports 50 (54%) of CC and 45 (48%) SCCS, 2 reports combined both designs. In 12 (24%) CC and 18 (40%) SCCS articles, all applicable validity assumptions of the designs were fulfilled, respectively. Fifty (54%) articles (15 CC (30%) and 35 (78%) SCCS) adequately addressed the specificities of the case-only analyses in the way they reported results. Our systematic review underlines that implementation of CC and SCCS designs needs to be more rigorous with regard to validity assumptions, as well as improvement in results reporting.

Several studies suggest that the number of risk factors rather than their nature is key to mental health disorders in childhood. The objective of this multicentre randomized controlled parallel trial (PROBE methodology) is to assess the impact in a multi-risk French urban sample of a home-visiting program targeting child mental health and its major determinants. This paper describes the protocol of this study. In the study, pregnant women were eligible if they were: living in the intervention area; able to speak French, less than 26 years old; having their first child; less than 27 weeks of amenorrhea; and if at least one of the following criteria were true: less than twelve years of education, intending to bring up their child without the presence of the child’s father, and 3) low income. Participants were randomized into either the intervention or the control group. All had access to usual care in mother-child centres and community mental health services free of charge in every neighbourhood. Psychologists conducted all home visits, which were planned on a weekly basis from the 7^th month of pregnancy and progressively decreasing in frequency until the child’s second birthday. Principle outcome measures included child mental health at 24 months and two major mediating variables for infant mental health: postnatal maternal depression and the quality of the caring environment. A total of 440 families were recruited, of which a subsample of 120 families received specific attachment and caregiver behaviour assessment. Assessment was conducted by an independent assessment team during home visits and, for the attachment study, in a specifically created Attachment Assessment laboratory. The CAPEDP study is the first large-scale randomised, controlled infant mental health promotion programme to take place in France. A major specificity of the program was that all home visits were conducted by specifically trained, supervised psychologists rather than nurses. Significant challenges included designing a mental health promotion programme targeting vulnerable families within one of the most generous but little assessed health and social care systems in the Western World. Current Clinical trial number is NCT00392847.

Objective: To estimate the minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries.Methods: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, and The Netherlands) 4‐week cohort study involving 1,532 patients who were prescribed nonsteroidal antiinflammatory drugs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis, or rheumatoid arthritis. The MCII and PASS values were estimated with the 75th percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability, and physician global assessment, all normalized to a 0–100 score.Results: For the whole sample, the estimated MCII values for absolute change at 4 weeks were −17 (95% confidence interval [95% CI] −18, −15) for pain; −15 (95% CI −16, −14) for patient global assessment; −12 (95% CI −13, −11) for functional disability assessment; and −14 (95% CI −15, −14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (95% CI 40, 44) for pain; 43 (95% CI 41, 45) for patient global assessment; 43 (95% CI 41, 44) for functional disability assessment; and 39 (95% CI 37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups ≥20 patients).Conclusion: This work allows for promoting the use of values of MCII (15 of 100 for absolute improvement, 20% for relative improvement) and PASS (40 of 100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function, or physician global assessment used as outcome criteria.

Introduction: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. Methods: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. Results: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). Conclusions: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.