Chronic postsurgical pain in Europe: An observational study.

BACKGROUND Chronic postsurgical pain (CPSP) is an important clinical problem. Prospective studies of the incidence, characteristics and risk factors of CPSP are needed. OBJECTIVES The objective of this study is to evaluate the incidence and risk factors of CPSP. DESIGN A multicentre, prospective, observational trial. SETTING Twenty-one hospitals in 11 European countries. PATIENTS Three thousand one hundred and twenty patients undergoing surgery and enrolled in the European registry PAIN OUT. MAIN OUTCOME MEASURES Pain-related outcome was evaluated on the first postoperative day (D1) using a standardised pain outcome questionnaire. Review at 6 and 12 months via e-mail or telephonic interview used the Brief Pain Inventory (BPI) and the DN4 (Douleur Neuropathique four questions). Primary endpoint was the incidence of moderate to severe CPSP (numeric rating scale, NRS ≥3/10) at 12 months. RESULTS For 1044 and 889 patients, complete data were available at 6 and 12 months. At 12 months, the incidence of moderate to severe CPSP was 11.8% (95% CI 9.7 to 13.9) and of severe pain (NRS ≥6) 2.2% (95% CI 1.2 to 3.3). Signs of neuropathic pain were recorded in 35.4% (95% CI 23.9 to 48.3) and 57.1% (95% CI 30.7 to 83.4) of patients with moderate and severe CPSP, respectively. Functional impairment (BPI) at 6 and 12 months increased with the severity of CPSP (P < 0.01) and presence of neuropathic characteristics (P < 0.001). Multivariate analysis identified orthopaedic surgery, preoperative chronic pain and percentage of time in severe pain on D1 as risk factors. A 10% increase in percentage of time in severe pain was associated with a 30% increase of CPSP incidence at 12 months. CONCLUSION The collection of data on CPSP was feasible within the European registry PAIN OUT. The incidence of moderate to severe CPSP at 12 months was 11.8%. Functional impairment was associated with CPSP severity and neuropathic characteristics. Risk factors for CPSP in the present study were chronic preoperative pain, orthopaedic surgery and percentage of time in severe pain on D1. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01467102.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still TOL. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03.

PURPOSE Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. RESULTS One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. CONCLUSION Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.