The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis

BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P=0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, −3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494. opens in new tab; ClinicalTrials.gov number, NCT00987389. opens in new tab.)Michael Walsh, Peter A. Merkel, Chen-Au Peh, Wladimir M. Szpirt, Xavier Puéchal, Shouichi Fujimoto ... et al

Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines

© 2017 The British Infection Association Objectives Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients with prolonged neutropenia. In consideration of a worldwide increase in antibiotic resistance, the issue of FQ prophylaxis during neutropenia was re-evaluated. Methods Literature review of randomised controlled trials (RCT) and observational studies published in years 2006–2014 was performed. Their results were analysed in meta-analysis. Meta-regression model was applied to evaluate whether the rates of FQ resistance in community and hospital settings influenced the efficacy of FQ prophylaxis. The impact of FQ prophylaxis on colonisation and infection with resistant bacteria was reviewed. Results Two RCTs and 12 observational studies were identified. FQ prophylaxis did not have effect on mortality (pooled OR 1.01, 95%CI 0.73–1.41), but was associated with lower rate of bloodstream infections (BSI) (pooled OR 0.57, 95%CI 0.43–0.74) and episodes of fever during neutropenia (pooled OR 0.32, 95%CI 0.20–0.50). No effect of the background rate of FQ resistance on the efficacy of FQ prophylaxis was observed. In few studies, FQ prophylaxis resulted in an increased colonisation or infection with FQ- or multi-drug resistant strains. Conclusions The possible benefits of FQ prophylaxis on BSI rate, but not on overall mortality, should be weighed against its impact in terms of toxicity and changes in local ecology in single centres.status: publishe

Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines

Objectives Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients with prolonged neutropenia. In consideration of a worldwide increase in antibiotic resistance, the issue of FQ prophylaxis during neutropenia was re-evaluated. Methods Literature review of randomised controlled trials (RCT) and observational studies published in years 2006\ue2\u80\u932014 was performed. Their results were analysed in meta-analysis. Meta-regression model was applied to evaluate whether the rates of FQ resistance in community and hospital settings influenced the efficacy of FQ prophylaxis. The impact of FQ prophylaxis on colonisation and infection with resistant bacteria was reviewed. Results Two RCTs and 12 observational studies were identified. FQ prophylaxis did not have effect on mortality (pooled OR 1.01, 95%CI 0.73\ue2\u80\u931.41), but was associated with lower rate of bloodstream infections (BSI) (pooled OR 0.57, 95%CI 0.43\ue2\u80\u930.74) and episodes of fever during neutropenia (pooled OR 0.32, 95%CI 0.20\ue2\u80\u930.50). No effect of the background rate of FQ resistance on the efficacy of FQ prophylaxis was observed. In few studies, FQ prophylaxis resulted in an increased colonisation or infection with FQ- or multi-drug resistant strains. Conclusions The possible benefits of FQ prophylaxis on BSI rate, but not on overall mortality, should be weighed against its impact in terms of toxicity and changes in local ecology in single centres

ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients

The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis

Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up

Introduction: The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Methods: Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Results: Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Discussion: Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial