Feasibility of Collecting Multiple Patient-Reported Outcome Measures Alongside the Dutch Arthroplasty Register.

BACKGROUND: Compliance rates with patient-reported outcome measures (PROMs) collected alongside arthroplasty registries vary in the literature. We described the feasibility of a routinely collected set PROMs alongside the Dutch Arthroplasty Register. METHODS: The longitudinal Leiden Orthopaedics Outcomes of OsteoArthritis Study is a multicenter (7 hospitals), observational study including patients undergoing total hip or total knee arthroplasty (THA or TKA). A set of PROMs: Short Form-12, EuroQol 5 Dimensions, Hip/Knee injury and Osteoarthritis Outcome Score, Oxford Hip/Knee Score was collected preoperatively and at 6, 12, 24 months, and every 2 years thereafter. Participation rates and response rates were recorded. RESULTS: Between June 2012 and December 2014, 1796 THA and 1636 TKA patients were invited, of whom 1043 THA (58%; mean age 68 years [standard deviation, SD: 10]) and 970 TKA patients (59%; mean age 71 years [SD 9.5]) participated in the study. At 6 months, 35 THA/38 TKA patients were lost to follow-up. Response rates were 90% for THA (898/1000) and 89% for TKA (827/932) participants. At 1 and 2 years, 8 and 18 THA and 17 and 11 TKA patients were lost to follow-up, respectively. The response rates among those eligible were 87% (866/992) and 84% (812/972) for THA and 84% (771/917) and 83% (756/906) for TKA patients, respectively. The 2-year questionnaire was completed by 78.5% of the included THA patients and by 77.9% of the included TKA patients. CONCLUSIONS: About 60% of patients undergoing THA or TKA complete PROMs preoperatively, with more than 80% returning follow-up PROMs. To increase the participation rates, more efforts concerning the initial recruitment of patients are needed.

Ototopical drops containing a novel antibacterial synthetic peptide: Safety and efficacy in adults with chronic suppurative otitis media.

OBJECTIVE: Chronic suppurative otitis media (CSOM) is a chronic infectious disease with worldwide prevalence that causes hearing loss and decreased quality of life. As current (antibiotic) treatments often unsuccessful and antibiotic resistance is emerging, alternative agents and/or strategies are urgently needed. We considered the synthetic antimicrobial and anti-biofilm peptide P60.4Ac to be an interesting candidate because it also displays anti-inflammatory activities including lipopolysaccharide-neutralizing activity. The aim of the present study was to investigate the safety and efficacy of ototopical drops containing P60.4Ac in adults with CSOM without cholesteatoma. METHODS: We conducted a range-finding study in 16 subjects followed by a randomized, double blinded, placebo-controlled, multicentre phase IIa study in 34 subjects. P60.4Ac-containing ototopical drops or placebo drops were applied twice a day for 2 weeks and adverse events (AEs) and medication use were recorded. Laboratory tests, swabs from the middle ear and throat for bacterial cultures, and audiometry were performed at intervals up to 10 weeks after therapy. Response to treatment was assessed by blinded symptom scoring on otoscopy. RESULTS: Application of P60.4Ac-containing ototopical drops (0.25-2.0 mg of peptide/ml) in the ear canal of patients suffering from CSOM was found to be safe and well-tolerated. The optimal dose (0.5 mg of peptide/ml) was selected for the subsequent phase IIa study. Safety evaluation revealed only a few AEs that were unlikely related to study treatment and all, except one, were of mild to moderate intensity. In addition to this excellent safety profile, P60.4Ac ototopical drops resulted in a treatment success in 47% of cases versus 6% in the placebo group. CONCLUSION: The efficacy/safety balance assessed in the present study provides a compelling justification for continued clinical development of P60.4Ac in therapy-resistant CSOM.

Pre-transplantation Risks and Transplant-Techniques in Haematopoietic Stem Cell Transplantation for Acute Leukaemia.

BACKGROUND: The role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres. METHODS: This Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50 years; 1-75 years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N = 8641; 95%) or matched unrelated donor (N = 462; 5%) for acute myeloid (N = 6432; 71%) or acute lymphoblastic (N = 2671; 29%) leukaemia in first complete remission, and reported by 240 centres in 30 countries to the benchmark database of the European Society for Blood and Marrow Transplantation (EBMT) searched for factors associated with use of transplant techniques (standard N = 6375;70% or reduced intensity conditioning N = 2728;30%, respectively bone marrow N = 1945;21% or peripheral blood N = 7158;79% as stem cell source), and their impact on outcome. FINDINGS: Treatment groups differed significantly from baseline population (p < 0.001), and within groups regarding patient-, disease-, donor-, and centre-related pre-transplantation risk factors (p < 0.001); choice of technique did depend on pre-transplantation risk factors and centre (p < 0.001). Probability of overall survival at 5 years decreased systematically and significantly with increasing pre-transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1-1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3-1·7], p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6-2·2], p < 0.001) with no significant differences between treatment groups (likelihood ratio test on interaction: p = 0.40). Overall survival was significantly associated with selection steps and completeness of information (p < 0.001). INTERPRETATION: Patients' pre-transplantation risk factors determine survival, independent of transplant techniques. Transplant techniques should be regarded as centre policy, not stratification factor in benchmarking. Selection criteria and completeness of data bias outcome. Outcomes may be improved more effectively through better identifying pre-transplantation factors as opposed to refinement of transplant techniques. FUNDING: The study was funded by EBMT.

Percutaneous laser disc decompression versus microdiscectomy for sciatica: Cost utility analysis alongside a randomized controlled trial.

Background Percutaneous laser disc decompression (PLDD) for patients with lumbar disc herniation is believed to be cheaper than surgery. However, cost-effectiveness has never been studied. Materials and Methods A cost utility analysis was performed alongside a randomized controlled trial comparing PLDD and conventional surgery. Patients reported their quality of life using the EuroQol five dimensions questionnaire (EQ-5D), 36-item short form health survey (SF-36 and derived SF-6D) and a visual analogue scale (VAS). Using cost diaries patients reported health care use, non-health care use and hours of absenteeism from work. The 1-year societal costs were compared with 1-year quality adjusted life years (QALYs) based on the United States (US) EQ-5D. Sensitivity analyses were carried out on the use of different utility measures (Netherland (NL) EQ-5D, SF-6D, or VAS) and on the perspective (societal or healthcare). Results On the US EQ-5D, conventional surgery provided a non-significant gain in QALYs of 0.033 (95% confidence interval (CI) -0.026 to 0.093) in the first year. PLDD resulted in significantly lower healthcare costs (difference €1771, 95% CI €303 to €3238) and non-significantly lower societal costs (difference €2379, 95% CI -€2860 to €7618). For low values of the willingness to pay for a QALY, the probability of being cost-effective is in favor of PLDD. For higher values of the willingness to pay, between €30,000 and €70,000, conventional microdiscectomy becomes favorable. Conclusions From a healthcare perspective PLDD, followed by surgery when needed, results in significantly lower 1-year costs than conventional surgery. From a societal perspective PLDD appears to be an economically neutral innovation.

Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).

Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Tubular discectomy versus conventional microdiscectomy for the treatment of lumbar disc herniation: long-term results of a randomised controlled trial.

BACKGROUND: The reference surgical procedure for the treatment of lumbar disc herniation is open microdiscectomy. Minimal invasive discectomy with tubular retractors is hypothesised to cause less tissue damage and result in lower blood loss, less postoperative pain and faster recovery. We previously reported our 1 and 2-year results, and found no better outcomes of tubular discectomy compared with open microdiscectomy. Until now, no studies on tubular discectomy have reported results with more than 2 years of follow-up. Studies with long-term follow-up are required to determine if clinical outcomes are sustained and to assess specific long-term outcomes such as reoperation rate and iatrogenic low back pain due to impaired spinal integrity. The aim of this study is to evaluate the 5-year results of tubular discectomy compared with conventional microdiscectomy. METHODS: The study was designed as a double-blind randomised controlled trial. 325 patients with a symptomatic lumbar disc herniation were randomly allocated to tubular discectomy (166 patients) or conventional microdiscectomy (159 patients). Repeated standardised follow-up measurements were performed at 2, 4, 6, 8, 12, 26, 38, 52, 78, 104, 156, 208 and 260 weeks after randomisation. Main outcomes are the Roland-Morris Disability Questionnaire for Sciatica (RDQ), Visual Analogue Scale for leg pain and low back pain, self-perceived recovery and reoperation incidence. RESULTS: There was no clinically significant difference between tubular discectomy and conventional microdiscectomy regarding the main clinical outcomes at any time point during the 5 years of follow-up. RDQ scores at 5 years were 4.3 (95% CI 3.3 to 5.2) in the tubular discectomy group and 3.4 (95% CI 2.4 to 4.5) in the conventional microdiscectomy group. The mean difference of 0.9 (95% CI -0.6 to 2.2) was not significant. Mean differences for leg pain and back pain were 0.2 (95% CI -5.5 to 6.0) and 0.4 (95% CI -5.9 to 6.7), respectively. 77% of patients allocated to conventional discectomy reported complete or near-complete recovery of symptoms compared with 74% of patients allocated to tubular discectomy (p=0.79). The reoperation rate was 18% in the tubular discectomy group and 13% in the conventional discectomy group (p=0.29). CONCLUSIONS: Long-term functional and clinical outcome did not differ between patients allocated to tubular discectomy and conventional microdiscectomy. Primary and secondary outcome measures did not support the hypothesised advantages of tubular discectomy over conventional microdiscectomy. TRIAL REGISTRATION NUMBER: ISRCTN51857546.

Percutaneous laser disc decompression versus conventional microdiscectomy for patients with sciatica: Two-year results of a randomised controlled trial.

Background Percutaneous laser disc decompression is a minimally invasive treatment, for lumbar disc herniation and might serve as an alternative to surgical management of sciatica. In a randomised trial with two-year follow-up we assessed the clinical effectiveness of percutaneous laser disc decompression compared to conventional surgery. Materials and methods This multicentre randomised prospective trial with a non-inferiority design, was carried out according to an intent-to-treat protocol with full institutional review board approval. One hundred and fifteen eligible surgical candidates, with sciatica from a disc herniation smaller than one-third of the spinal canal, were randomly allocated to percutaneous laser disc decompression ( n = 55) or conventional surgery ( n = 57). The main outcome measures for this trial were the Roland-Morris Disability Questionnaire for sciatica, visual analogue scores for back and leg pain and the patient's report of perceived recovery. Results The primary outcome measures showed no significant difference or clinically relevant difference between the two groups at two-year follow-up. The re-operation rate was 21% in the surgery group, which is relatively high, and with an even higher 52% in the percutaneous laser disc decompression group. Conclusion At two-year follow-up, a strategy of percutaneous laser disc decompression, followed by surgery if needed, resulted in non-inferior outcomes compared to a strategy of microdiscectomy. Although the rate of reoperation in the percutaneous laser disc decompression group was higher than expected, surgery could be avoided in 48% of those patients that were originally candidates for surgery. Percutaneous laser disc decompression, as a non-surgical method, could have a place in the treatment arsenal of sciatica caused by contained herniated discs.

Percutaneous laser disc decompression versus conventional microdiscectomy in sciatica: a randomized controlled trial.

BACKGROUND CONTEXT: Percutaneous laser disc decompression (PLDD) is a minimally invasive treatment for lumbar disc herniation, with Food and Drug Administration approval since 1991. However, no randomized trial comparing PLDD to conventional treatment has been performed. PURPOSE: In this trial, we assessed the effectiveness of a strategy of PLDD as compared with conventional surgery. STUDY DESIGN/SETTING: This randomized prospective trial with a noninferiority design was carried out in two academic and six teaching hospitals in the Netherlands according to an intent-to-treat protocol with full institutional review board approval. PATIENT SAMPLE: One hundred fifteen eligible surgical candidates, with sciatica from a disc herniation smaller than one-third of the spinal canal, were included. OUTCOME MEASURES: The main outcome measures for this trial were the Roland-Morris Disability Questionnaire for sciatica, visual analog scores for back and leg pain, and the patient's report of perceived recovery. METHODS: Patients were randomly allocated to PLDD (n=57) or conventional surgery (n=58). Blinding was impossible because of the nature of the interventions. This study was funded by the Healthcare Insurance Board of the Netherlands. RESULTS: The primary outcome, Roland-Morris Disability Questionnaire, showed noninferiority of PLDD at 8 (-0.1; [95% confidence interval (CI), -2.3 to 2.1]) and 52 weeks (-1.1; 95% CI, -3.4 to 1.1) compared with conventional surgery. There was, however, a higher speed of recovery in favor of conventional surgery (hazard ratio, 0.64 [95% CI, 0.42-0.97]). The number of reoperations was significantly less in the conventional surgery group (38% vs. 16%). Overall, a strategy of PLDD, with delayed surgery if needed, resulted in noninferior outcomes at 1 year. CONCLUSIONS: At 1 year, a strategy of PLDD, followed by surgery if needed, resulted in noninferior outcomes compared with surgery.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Assessment of patient-specific surgery effect based on weighted estimation and propensity scoring in the re-analysis of the sciatica trial.

We consider a re-analysis of the wait-and-see (control) arm of a recent clinical trial on sciatica. While the original randomised trial was designed to evaluate the public policy effect of a conservative wait-and-see approach versus early surgery, we investigate the impact of surgery at the individual patient level in a re-analysis of the wait-and-see group data. Both marginal structural model re-weighted estimates as well as propensity score adjusted analyses are presented. Results indicate that patients with high propensity to receive surgery may have beneficial effects at 2 years from delayed disc surgery.

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages.

Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide.

BACKGROUND: Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. STUDY DESIGN AND METHODS: In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. RESULTS: While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. CONCLUSION: We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

BACKGROUND: The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. METHODS: A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. RESULTS: Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. CONCLUSIONS: We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen.

CASINO: surgical or nonsurgical treatment for cervical radiculopathy, a randomised controlled trial.

BACKGROUND: Cervical radicular syndrome (CRS) due to a herniated disc can be safely treated by surgical decompression of the spinal root. In the vast majority of cases this relieves pain in the arm and restores function. However, conservative treatment also has a high chance on relieving symptoms. The objective of the present study is to evaluate the (cost-) effectiveness of surgery versus prolonged conservative care during one year of follow-up, and to evaluate the timing of surgery. Predisposing factors in favour of one of the two treatments will be evaluated. METHODS/DESIGN: Patients with disabling radicular arm pain, suffering for at least 2 months, and an MRI-proven herniated cervical disc will be randomised to receive either surgery or prolonged conservative care with surgery if needed. The surgical intervention will be an anterior discectomy or a posterior foraminotomy that is carried out according to usual care. Surgery will take place within 2-4 weeks after randomisation. Conservative care starts immediately after randomisation. The primary outcome measure is the VAS for pain or tingling sensations in the arm one year after randomisation. In addition, timing of surgery will be studied by correlating the primary outcome to the duration of symptoms. Secondary outcome measures encompass quality of life, costs and perceived recovery. Predefined prognostic factors will be evaluated. The total follow-up period will cover two years. A sample size of 400 patients is needed. Statistical analysis will be performed using a linear mixed model which will be based on the 'intention to treat' principle. In addition, a new CRS questionnaire for patients will be developed, the Leiden Cervical Radicular Syndrome Functioning (LCRSF) scale. DISCUSSION: The outcome will contribute to better decision making for the treatment of cervical radicular syndrome. TRIAL REGISTRATION: NTR3504.

Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.

Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures.

Patient blood management in elective total hip- and knee-replacement surgery (Part 1): a randomized controlled trial on erythropoietin and blood salvage as transfusion alternatives using a restrictive transfusion policy in erythropoietin-eligible patients.

BACKGROUND: Patient blood management combines the use of several transfusion alternatives. Integrated use of erythropoietin, cell saver, and/or postoperative drain reinfusion devices on allogeneic erythrocyte use was evaluated using a restrictive transfusion threshold. METHODS: In a factorial design, adult elective hip- and knee-surgery patients with hemoglobin levels 10 to 13 g/dl (n = 683) were randomized for erythropoietin or not, and subsequently for autologous reinfusion by cell saver or postoperative drain reinfusion devices or for no blood salvage device. Primary outcomes were mean allogeneic intra- and postoperative erythrocyte use and proportion of transfused patients (transfusion rate). Secondary outcome was cost-effectiveness. RESULTS: With erythropoietin (n = 339), mean erythrocyte use was 0.50 units (U)/patient and transfusion rate 16% while without (n = 344), these were 0.71 U/patient and 26%, respectively. Consequently, erythropoietin resulted in a nonsignificant 29% mean erythrocyte reduction (ratio, 0.71; 95% CI, 0.42 to 1.13) and 50% reduction of transfused patients (odds ratio, 0.5; 95% CI, 0.35 to 0.75). Erythropoietin increased costs by €785 per patient (95% CI, 262 to 1,309), that is, €7,300 per avoided transfusion (95% CI, 1,900 to 24,000). With autologous reinfusion, mean erythrocyte use was 0.65 U/patient and transfusion rate was 19% with erythropoietin (n = 214) and 0.76 U/patient and 29% without (n = 206). Compared with controls, autologous blood reinfusion did not result in erythrocyte reduction and increased costs by €537 per patient (95% CI, 45 to 1,030). CONCLUSIONS: In hip- and knee-replacement patients (hemoglobin level, 10 to 13 g/dl), even with a restrictive transfusion trigger, erythropoietin significantly avoids transfusion, however, at unacceptably high costs. Autologous blood salvage devices were not effective.

Patient blood management in elective total hip- and knee-replacement surgery (part 2): a randomized controlled trial on blood salvage as transfusion alternative using a restrictive transfusion policy in patients with a preoperative hemoglobin above 13 g/dl.

BACKGROUND: Patient blood management is introduced as a new concept that involves the combined use of transfusion alternatives. In elective adult total hip- or knee-replacement surgery patients, the authors conducted a large randomized study on the integrated use of erythropoietin, cell saver, and/or postoperative drain reinfusion devices (DRAIN) to evaluate allogeneic erythrocyte use, while applying a restrictive transfusion threshold. Patients with a preoperative hemoglobin level greater than 13 g/dl were ineligible for erythropoietin and evaluated for the effect of autologous blood reinfusion. METHODS: Patients were randomized between autologous reinfusion by cell saver or DRAIN or no blood salvage device. Primary outcomes were mean intra- and postoperative erythrocyte use and proportion of transfused patients (transfusion rate). Secondary outcome was cost-effectiveness. RESULTS: In 1,759 evaluated total hip- and knee-replacement surgery patients, the mean erythrocyte use was 0.19 (SD, 0.9) erythrocyte units/patient in the autologous group (n = 1,061) and 0.22 (0.9) erythrocyte units/patient in the control group (n = 698) (P = 0.64). The transfusion rate was 7.7% in the autologous group compared with 8.3% in the control group (P = 0.19). No difference in erythrocyte use was found between cell saver and DRAIN groups. Costs were increased by €298 per patient (95% CI, 76 to 520). CONCLUSION: In patients with preoperative hemoglobin levels greater than 13 g/dl, autologous intra- and postoperative blood salvage devices were not effective as transfusion alternatives: use of these devices did not reduce erythrocyte use and increased costs.

Randomized, multicenter trial to assess the efficacy, safety and tolerability of a single dose of a novel AMPA receptor antagonist BGG492 for the treatment of acute migraine attacks.

BACKGROUND: Glutamate is implicated in migraine pathophysiology; amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists represent a potential therapeutic approach because of their anti-excitatory actions. METHODS: This randomized, double-blind, proof-of-concept study assessed the efficacy of the AMPA receptor antagonist, BGG492 (250 mg), vs placebo and sumatriptan (100 mg), in 75 subjects with acute migraine attacks. Efficacy was measured using the Patient Migraine Diary. Pharmacokinetic and safety data were collected. RESULTS: Improvement from severe/moderate to mild/no headache pain (primary response) was reported in 58%, 58%, and 54% of BGG492-treated subjects at 2, 3, and 4 hours post-dose ( P = 0.2, 0.5, and 0.5 vs placebo), respectively, compared with 68%, 84%, and 92% sumatriptan-treated subjects, and 40%, 48%, and 44% in the placebo group. Percentages of subjects with ≥ 2-point improvement in pain score from baseline at 2 hours were 29%, 40%, and 16% for BGG492, sumatriptan, and placebo, respectively. Pain-free response at 2 hours was reported for 25%, 24%, and 16% of BGG492, sumatriptan, and placebo subjects, respectively. Adverse events were reported by 80%, 56%, and 60% of BGG492, sumatriptan, and placebo subjects, respectively. CONCLUSIONS: Proof-of-concept criterion was not met (≥ 25% BGG492 subjects with a primary response vs placebo at two timepoints). BGG492 was comparable to sumatriptan in terms of pain-free response.

Recovery of motor deficit accompanying sciatica--subgroup analysis of a randomized controlled trial.

BACKGROUND CONTEXT: In patients with sciatica due to a lumbar disc herniation, it is generally recommended to reserve surgical treatment for those who suffer from intolerable pain or those who demonstrate persistent symptoms after conservative management. Controversy exists about the necessity of early surgical intervention for those patients that have an additional motor deficit. PURPOSE: The aim of this study was to compare the recovery of motor deficit among patients receiving early surgery to those receiving prolonged conservative treatment. STUDY DESIGN: Subgroup analysis of a randomized controlled trial. PATIENT SAMPLE: This subgroup analysis focuses on 150 (53%) of 283 patients with sciatica due to a lumbar disc herniation and whose symptoms at baseline (before randomization) were accompanied by a motor deficit. OUTCOME MEASURES: Motor deficit was assessed through manual muscle testing and graded according to the Medical Research Council (MRC) scale. METHODS: In total, 150 patients with 6 to 12 weeks of sciatica due to a lumbar disc herniation and whose symptoms were accompanied by a moderate (MRC Grade 4) or severe (MRC Grade 3) motor deficit were randomly allocated to early surgery or prolonged conservative treatment. Repeated standardized neurologic examinations were performed at baseline and at 8, 26, and 52 weeks after randomization. This study was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMW) and the Hoelen Foundation The Hague. RESULTS: Sciatica recovered among seven (10%) of the 70 patients assigned to early surgery before surgery could be performed, and of the 80 patients assigned to conservative treatment, 32 patients (40%) were treated surgically because of intolerable pain. Baseline severity of motor deficit was graded moderate in 84% of patients and severe in 16% of patients. Motor deficit recovered significantly faster among patients allocated to early surgery (p=.01), but the difference was no longer significant at 26 (p=.21) or 52 weeks (p=.92). At 1 year, complete recovery of motor deficit was found in 81% of patients allocated to early surgery and in 80% of patients allocated to prolonged conservative treatment. Perceived overall recovery of sciatica was directly related to the presence of an accompanying motor deficit. Severe motor deficit at baseline (odds ratio, 5.4; confidence interval, 1.7-17.4) and a lumbar disc herniation encompassing ≥25% of the cross-sectional area of the spinal canal (odds ratio, 6.4; confidence interval, 1.3-31.8) were the most important risk factors for persistent deficit at 1 year. CONCLUSIONS: Early surgery resulted in a faster recovery of motor deficit accompanying sciatica compared with prolonged conservative treatment but the difference was no longer significant during the final follow-up examination at 1 year.