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Sample records for non-comparative multicenter phase

  1. Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.

    PubMed

    O'Brien, Terence J; Ben-Menachem, Elinor; Bertram, Edward H; Collins, Stephen D; Kokaia, Merab; Lerche, Holger; Klitgaard, Henrik; Staley, Kevin J; Vaudano, Elisabetta; Walker, Matthew C; Simonato, Michele

    2013-08-01

    There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.

  2. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

    PubMed Central

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-01-01

    Background Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. Design and Methods This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1–4, prednisone at a dose of 1.5 mg/kg also on days 1–4 and thalidomide at a dose of 50–100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1–4 and 1.6, 3.2, or 4.8 g on days 5–35. Results Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3–4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. Conclusions This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1–4 followed by 4.8 g p.o. on days 5–35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs (ClinicalTrials.gov Identifier: NCT00406978). PMID:20053869

  3. Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: a multicenter retrospective study.

    PubMed

    Zvulunov, Alex; McCuaig, Catherine; Frieden, Ilona J; Mancini, Anthony J; Puttgen, Kate B; Dohil, Magdalene; Fischer, Gayle; Powell, Julie; Cohen, Bernard; Ben Amitai, Dan

    2011-01-01

    Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting.

  4. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.

    PubMed

    Bringhen, Sara; Petrucci, Maria Teresa; Larocca, Alessandra; Conticello, Concetta; Rossi, Davide; Magarotto, Valeria; Musto, Pellegrino; Boccadifuoco, Luana; Offidani, Massimo; Omedé, Paola; Gentilini, Fabiana; Ciccone, Giovannino; Benevolo, Giulia; Genuardi, Mariella; Montefusco, Vittorio; Oliva, Stefania; Caravita, Tommaso; Tacchetti, Paola; Boccadoro, Mario; Sonneveld, Pieter; Palumbo, Antonio

    2014-07-03

    This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787.

  5. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma.

    PubMed

    Fehniger, Todd A; Larson, Sarah; Trinkaus, Kathryn; Siegel, Marilyn J; Cashen, Amanda F; Blum, Kristie A; Fenske, Timothy S; Hurd, David D; Goy, Andre; Schneider, Stephanie E; Keppel, Catherine R; Wagner-Johnston, Nina D; Carson, Kenneth R; Bartlett, Nancy L

    2011-11-10

    Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

  6. Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

    SciTech Connect

    Muecke, Ralph; Schomburg, Lutz; Glatzel, Michael; Berndt-Skorka, Regina; Baaske, Dieter; Reichl, Berthold; Buentzel, Jens; Kundt, Guenter; Prott, Franz J.; Vries, Alexander de; Stoll, Guenther; Kisters, Klaus; Bruns, Frank; Schaefer, Ulrich; Willich, Norman; Micke, Oliver

    2010-11-01

    Purpose: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. Methods and Materials: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84{mu}g/L were randomized before RT either to receive 500 {mu}g of selenium (in the form of sodium selenite [selenase (registered) , biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 {mu}g of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. Results: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. Conclusions: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

  7. A multicenter phase II study of irinotecan in patients with advanced colorectal cancer previously treated with 5-fluorouracil.

    PubMed

    Méndez, Miguel; Salut, Antonieta; García-Girón, Carlos; Navalon, Marta; Diz, Pilar; García López, Maria José; España, Pilar; de la Torre, Ascensión; Martínez del Prado, Purificación; Duarte, Isabel; Pujol, Eduardo; Arizcun, Alberto; Cruz, Juan Jesús

    2003-11-01

    This multicenter, open-label, phase II study was performed to assess the efficacy and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU). The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient) were administered. The overall objective response rate on an intent-to-treat basis was 18% (with 1 complete response and 20 partial responses), whereas 42 patients (37%) showed stable disease. Median time to progression was 4.8 months and median survival was 13.6 months. Grade 3/4 toxicities included delayed diarrhea (19.1%), nausea/vomiting (10.4%), and neutropenia (8.7%). There were 2 toxic deaths, 1 from delayed diarrhea and 1 from hemorrhage and grade 4 mucositis. In conclusion, the present study confirms the antitumor efficacy of irinotecan monotherapy in patients with CRC pretreated with 5-FU.

  8. 2D harmonic filtering of MR phase images in multicenter clinical setting: toward a magnetic signature of cerebral microbleeds.

    PubMed

    Kaaouana, Takoua; de Rochefort, Ludovic; Samaille, Thomas; Thiery, Nathalie; Dufouil, Carole; Delmaire, Christine; Dormont, Didier; Chupin, Marie

    2015-01-01

    Cerebral microbleeds (CMBs) have emerged as a new imaging marker of small vessel disease. Composed of hemosiderin, CMBs are paramagnetic and can be detected with MRI sequences sensitive to magnetic susceptibility (typically, gradient recalled echo T2* weighted images). Nevertheless, their identification remains challenging on T2* magnitude images because of confounding structures and lesions. In this context, T2* phase image may play a key role in better characterizing CMBs because of its direct relationship with local magnetic field variations due to magnetic susceptibility difference. To address this issue, susceptibility-based imaging techniques were proposed, such as Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM). But these techniques have not yet been validated for 2D clinical data in multicenter settings. Here, we introduce 2DHF, a fast 2D phase processing technique embedding both unwrapping and harmonic filtering designed for data acquired in 2D, even with slice-to-slice inconsistencies. This method results in internal field maps which reveal local field details due to magnetic inhomogeneity within the region of interest only. This technique is based on the physical properties of the induced magnetic field and should yield consistent results. A synthetic phantom was created for numerical simulations. It simulates paramagnetic and diamagnetic lesions within a 'brain-like' tissue, within a background. The method was evaluated on both this synthetic phantom and multicenter 2D datasets acquired in standardized clinical setting, and compared with two state-of-the-art methods. It proved to yield consistent results on synthetic images and to be applicable and robust on patient data. As a proof-of-concept, we finally illustrate that it is possible to find a magnetic signature of CMBs and CMCs on internal field maps generated with 2DHF on 2D clinical datasets that give consistent results with CT-scans in a subsample of 10 subjects

  9. Interventions to Increase Enrollment in a Large Multicenter Phase 3 Trial of Carotid Stenting versus Endarterectomy

    PubMed Central

    Longbottom, Mary E.; Roberts, Jamie N.; Tom, MeeLee; Hughes, Susan E.; Howard, Virginia J.; Sheffet, Alice J.; Meschia, James F.; Brott, Thomas G.

    2012-01-01

    Background Randomized clinical trials often encounter slow enrollment. Failing to meet sample size requirements has scientific, financial, and ethical implications. Aims We report interventions used to accelerate recruitment in a large multicenter clinical trial that was not meeting prespecified enrollment commitments. Methods The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) began randomization in December 2000. To accelerate enrollment, multiple recruitment tactics were initiated, which included expanding the number of sites; hiring a Recruitment Director (May 2003); broadening eligibility criteria (April 2005); branding with a study logo, website, and recruitment materials; increasing site visits by study leadership; sending emails to the site teams after every enrollment; distributing electronic newsletters; and implementing investigator and coordinator conferences. Results From December 2000 through May 2003, 14 sites became active (54 patients randomized); from June 2003 through April 2005, 44 sites were added (404 patients randomized); and from May 2005 through July 2008, 54 sites were added (2044 patients randomized). During these time intervals, the number of patients enrolled per site per year was 1.5, 3.6, and 5.6. For the single years 2004 to 2008, the mean monthly randomization rates per year were 19.7, 38.1, 56.4, 53.0, and 54.7 (annualized), respectively. Enrollment was highest after recruitment tactics were implemented: 677 patients in 2006, 636 in 2007, and 657 in 2008 (annualized). The prespecified sample size of 2502 patients, 47% asymptomatic, was accomplished July 2008. Conclusions Aggressive recruitment tactics and investment in a full-time Recruitment Director who can lead implementation may be effective in accelerating recruitment in multicenter trials. PMID:22631861

  10. Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post–allogeneic HCT

    PubMed Central

    Abu Zaid, Mohammad; Wu, Juan; Wu, Cindy; Logan, Brent R.; Yu, Jeffrey; Cutler, Corey; Antin, Joseph H.; Paczesny, Sophie

    2017-01-01

    A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT. We measured biomarkers from plasma samples collected in 211 patients using enzyme-linked immunosorbent assay (Tac/Sir = 104, Tac/Mtx = 107). High suppression of tumorigenicity-2 (ST2) and T-cell immunoglobulin mucin-3 (TIM3) at day 28 correlated with 2-year nonrelapse mortality in multivariate analysis (P = .0050, P = .0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49–3.95], P = .0038 and 4.87 [2.53–9.34], P < .0001, respectively). High ST2 and TIM3 correlated with overall survival. Chemokine (C-X-C motif) ligand 9 (CXCL9) levels above the median were associated with chronic GVHD compared with levels below the median in a time-dependent proportional hazard analysis (P = .0069). Low L-Ficolin was associated with hepatic veno-occlusive disease (P = .0053, AUC = 0.80). We confirmed the correlation of plasma-derived proteins, previously assessed in single-center cohorts, with clinical outcomes after allogeneic HCT within this prospective, multicenter study. PMID:27827824

  11. Phase 1 Multicenter Study of Vincristine Sulfate Liposomes Injection and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia

    PubMed Central

    Thomas, Deborah A.; Kantarjian, Hagop M.; Stock, Wendy; Heffner, Leonard T.; Faderl, Stefan; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Wierda, William; Pierce, Sherry; Lu, Biao; Deitcher, Steven R.; O’Brien, Susan

    2015-01-01

    BACKGROUND Dose intensification of chemotherapy has improved outcome for younger adults with de novo acute lymphoblastic leukemia (ALL). Novel formulations of standard chemotherapy agents may further reduce the incidence of disease recurrence after frontline chemotherapy. Vincristine (VCR) sulfate liposomes injection (VSLI) is a sphingomyelin/cholesterol nanoparticle encapsulated VCR formulation that improves the pharmacokinetic profile of VCR without augmenting neurotoxicity. METHODS A phase 1 trial of weekly, intravenous VSLI at 1.5 mg/m2, 1.825 mg/m2, 2.0 mg/m2, 2.25 mg/m2, or 2.4 mg/m2 was conducted to determine the maximum tolerated dose (MTD) using a standard, 3 + 3 dose-escalation design. Dexamethasone (40 mg) was given on Days 1 through 4 and on Days 11 through 14 of each 4-week cycle. RESULTS Thirty-six adults with relapsed/refractory ALL, all previously treated with conventional VCR, received at least 1 dose of VSLI. The MTD of VSLI was 2.25 mg/m2 based on dose-limiting toxicities of grade 3 motor neuropathy, grade 4 seizure, and grade 4 hepatotoxicity in 1 patient each at the 2.4 mg/m2 dose level. The most common toxicities attributed to VSLI included peripheral neuropathy (55%) and constipation (53%). A complete response (CR) was achieved in 7 of 36 patients (19%) based on an intent-to-treat analysis; the CR rate was 29% for the 14 patients who underwent therapy as their first salvage attempt. Four of 7 patients who achieved a CR underwent subsequent allogeneic stem cell transplantation in remission. CONCLUSIONS In this study, VSLI plus dexamethasone appeared to be an effective salvage therapy option for relapsed/refractory ALL. A phase 2, international, multicenter clinical trial assessing the efficacy of single-agent VSLI as second salvage therapy for patients with previously treated ALL is underway. PMID:19708032

  12. Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors.

    PubMed

    Minami, Hironobu; Ando, Yuichi; Ma, Brigette Buig Yue; Hsiang Lee, Jih-; Momota, Hiroyuki; Fujiwara, Yutaka; Li, Leung; Fukino, Koichi; Ito, Koji; Tajima, Takeshi; Mori, Asuka; Lin, Chia-Chi

    2016-10-01

    Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose-limiting toxicity (DLT) and the recommended dose (RD) of sonidegib in Asian patients with advanced solid tumors. This was an open-label, single-arm, multicenter, two-group, parallel, dose-escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on DLTs in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the DLT in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The RD of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The RD in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with Clinicaltrials.gov: NCT01208831.).

  13. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection

    PubMed Central

    Nord, Carl Erik; Talbot, George H.; Wilcox, Mark; Gerding, Dale N.; Buitrago, Martha; Kracker, Hilke; Charef, Pascal; Cornely, Oliver A.

    2015-01-01

    Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.) PMID:26248357

  14. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

    PubMed Central

    2014-01-01

    Background In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. Methods/design GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study

  15. A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale

    PubMed Central

    Drabik, Attyla; Hillgruber, Carina

    2014-01-01

    Background Livedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted. Objective The aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy. Methods We performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks. Results Enrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014. Conclusions Livedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa–dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis. Trial Registration Trial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical

  16. Low-level laser therapy in chemo- and radiation-induced mucositis: results of multicenter phase III studies

    NASA Astrophysics Data System (ADS)

    Bensadoun, Rene-Jean

    2001-04-01

    Low of middle energy irradiation with helium-neon laser (LLLT) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings obtained by Ciais et al prompted randomized multi-center, double-blind trials to evaluate LLLT for the prevention of a acute chemo- and radiation- induced stomatitis. Irradiation by LLLT corresponds to local application of a high photon density monochromatic light source. Activation of epithelial healing on LLL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies, and is a function of cell type, wavelength, and energy dose. The mechanism of action at a molecular and enzymatic level is currently being studied (detoxification of free-radicals).

  17. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    PubMed

    Heigener, David F; Pereira, José Rodrigues; Felip, Enriqueta; Mazal, Juraj; Manzyuk, Lyudmila; Tan, Eng Huat; Merimsky, Ofer; Sarholz, Barbara; Esser, Regina; Gatzemeier, Ulrich

    2015-06-01

    The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.

  18. Eligibility for mechanical thrombectomy in acute ischemic stroke: A phase IV multi-center screening log registry.

    PubMed

    Tsivgoulis, Georgios; Goyal, Nitin; Mikulik, Robert; Sharma, Vijay K; Katsanos, Aristeidis H; Zand, Ramin; Paliwal, Prakash R; Roussopoulou, Andromachi; Volny, Ondrej; Pandhi, Abhi; Zompola, Christina; Elijovich, Lucas; Safouris, Apostolos; Chang, Jason; Alexandrov, Andrei V; Alexandrov, Anne W

    2016-12-15

    No eligibility screening logs were kept in recent mechanical thrombectomy (MT) RCTs establishing safety and efficacy of endovascular reperfusion therapies for acute ischemic stroke (AIS). We sought to evaluate the potential eligibility for MT among consecutive AIS patients in a prospective international multicenter study. We prospectively evaluated consecutive AIS patients admitted in four tertiary-care stroke centers during a twelve-month period. Potential eligibility for MT was evaluated using inclusion criteria from MR CLEAN & REVASCAT. Our study population consisted of 1464 AIS patients (mean age 67±14years, 56% men, median admission NIHSS-score: 5, IQR: 3-10). A total of 123 (8%, 95% CI: 7%-10%) and 82 (6%, 95% CI: 5%-7%) patients fulfilled the inclusion criteria for MR CLEAN&REVASCAT respectively. No evidence of heterogeneity (p>0.100) was found in the eligibility for MT across the participating centers. Absence of proximal intracranial occlusion (69%) and hospital arrival outside the eligible time window (38% for MR CLEAN & 35% for REVASCAT) were the two most common reasons for ineligibility for MT. Our everyday clinical practice experience suggests that approximately one out of thirteen to seventeen consecutive AIS may be eligible for MT if inclusion criteria for MR CLEAN and REVASCAT are strictly adhered to.

  19. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  20. Combined-modality therapy for primary central nervous system lymphoma: Long-term data from a Phase II multicenter study (Trans-Tasman Radiation Oncology Group)

    SciTech Connect

    O'Brien, Peter C. . E-mail: Peter.OBrien@mater.health.nsw.gov.au; Roos, Daniel E.; Pratt, Gary; Liew, K.-H.; Barton, Michael B.; Poulsen, Michael G.; Olver, Ian N.; Trotter, Grant E.

    2006-02-01

    Purpose: To assess, in a multicenter setting, the long-term outcomes of a brief course of high-dose methotrexate followed by radiotherapy for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Forty-six patients were entered in a Phase II protocol consisting of methotrexate (1 g/m{sup 2} on Days 1 and 8), followed by whole-brain irradiation (45-50.4 Gy). The median follow-up time was 7 years, with a minimum follow-up of 5 years. Results: The 5-year survival estimate was 37% ({+-}14%, 95% confidence interval [CI]), with progression-free survival being 36% ({+-}15%, 95% CI), and median survival 36 months. Of the original 46 patients, 10 were alive, all without evidence of disease recurrence. A total of 11 patients have developed neurotoxicity, with the actuarial risk being 30% ({+-}18%, 95% CI) at 5 years but continuing to increase. For patients aged >60 years the risk of neurotoxicity at 7 years was 58% ({+-}30%, 95% CI). Conclusion: Combined-modality therapy, based on high-dose methotrexate, results in improved survival outcomes in PCNSL. The risk of neurotoxicity for patients aged >60 years is unacceptable with this regimen, although survival outcomes for patients aged >60 years were higher than in many other series.

  1. Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.

    PubMed

    Watanabe, Shinichi; Kishida, Hiroshi; Okubo, Akihiro

    2017-03-23

    Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

  2. Prospective Multicenter Phase II Trial of Systemic ADH-1 in Combination With Melphalan via Isolated Limb Infusion in Patients With Advanced Extremity Melanoma

    PubMed Central

    Beasley, Georgia M.; Riboh, Jonathan C.; Augustine, Christina K.; Zager, Jonathan S.; Hochwald, Steven N.; Grobmyer, Stephen R.; Peterson, Bercedis; Royal, Richard; Ross, Merrick I.; Tyler, Douglas S.

    2011-01-01

    Purpose Isolated limb infusion (ILI) with melphalan (M-ILI) dosing corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit melanoma with a 29% complete response rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes. In a preclinical animal model, systemic ADH-1 given with regional melphalan demonstrated synergistic antitumor activity, and in a phase I trial with M-ILI it had minimal toxicity. Patients and Methods Patients with American Joint Committee on Cancer (AJCC) stage IIIB or IIIC extremity melanoma were treated with 4,000 mg of ADH-1, administered systemically on days 1 and 8, and with M-ILI corrected for IBW on day 1. Drug pharmacokinetics and N-cadherin immunohistochemical staining were performed on pretreatment tumor. The primary end point was response at 12 weeks determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results In all, 45 patients were enrolled over 15 months at four institutions. In-field responses included 17 patients with complete responses (CRs; 38%), 10 with partial responses (22%), six with stable disease (13%), eight with progressive disease (18%), and four (9%) who were not evaluable. Median duration of in-field response among the 17 CRs was 5 months, and median time to in-field progression among 41 evaluable patients was 4.6 months (95% CI, 4.0 to 7.1 months). N-cadherin was detected in 20 (69%) of 29 tumor samples. Grade 4 toxicities included creatinine phosphokinase increase (four patients), arterial injury (one), neutropenia (one), and pneumonitis (one). Conclusion To the best of our knowledge, this phase II trial is the first prospective multicenter ILI trial and the first to incorporate a targeted agent in an attempt to augment antitumor responses to regional chemotherapy. Although targeting N-cadherin may improve melanoma sensitivity to chemotherapy, no difference in response to treatment was seen in this study. PMID:21343562

  3. Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

    PubMed Central

    Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

    2015-01-01

    BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

  4. Final Results of EFC6663: A Multicenter, International, Phase 2 Study of Alvocidib for Patients with Fludarabine-Refractory Chronic Lymphocytic Leukemia

    PubMed Central

    Lanasa, Mark C.; Andritsos, Leslie; Brown, Jennifer R.; Gabrilove, Janice; Caligaris, Federico -Cappio; Ghia, Paolo; Larson, Richard A.; Kipps, Thomas J.; Leblond, Veronique; Milligan, Donald W.; Janssens, Ann; Johnson, Amy J.; Heerema, Nyla A.; Bühler, Andreas; Stilgenbauer, Stephan; Devin, Jeanne; Hallek, Michael; Byrd, John C.; Grever, Michael R.

    2015-01-01

    Purpose Chronic lymphocytic leukemia (CLL) patients refractory to fludarabine based therapies have poor outcomes with currently available therapies. Early phase studies of alvocidib showed activity in relapsed CLL including patients with high risk genomic features and those refractory to fludarabine. A multi-center, international, phase II study of alvocidib in fludarabine refractory CLL was undertaken to validate these early results. Patients and Methods Patients with fludarabine refractory CLL or prolymphocytic leukemia arising from CLL were treated with single agent alvocidib. The primary outcome measure was overall response rate, with secondary outcomes including survival, toxicity, and response duration. Results One hundred and sixty five patients were enrolled at 34 centers, and 159 patients were treated. The median age was 61 years, the median number of prior therapies was 4, and 96% of patients were fludarabine refractory. The investigator-assessed overall response rate was 25%; the majority of responses were partial. Response rates were lower among patients with del(17p) (14%), but equivalent in patients with del(11q) or bulky lymphadenopathy. Median progression free and overall survival were 7.6 and 14.6 months respectively. Tumor lysis occurred in 39 patients (25%), and 13 received hemodialysis. Diarrhea, fatigue, and hematologic toxicities were common. Conclusion Alvocidib has clinical activity in patients with advanced, fludarabine refractory CLL. Clinical responses were observed in patients with high risk clinical and genomic features. With careful monitoring, alvocidib has a manageable safety profile. Future studies should focus on discovery of biomarkers of clinical response and tumor lysis, and enhanced supportive care measures. PMID:25804339

  5. Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis.

    PubMed

    Deterding, Robin; Retsch-Bogart, George; Milgram, Laura; Gibson, Ron; Daines, Cori; Zeitlin, Pamela L; Milla, Carlos; Marshall, Bruce; Lavange, Lisa; Engels, Jean; Mathews, Dave; Gorden, Joann; Schaberg, Amy; Williams, Judy; Ramsey, Bonnie

    2005-04-01

    Denufosol tetrasodium (INS37217) is a selective P2Y(2) agonist that stimulates ciliary beat frequency and Cl(-) secretion in normal and cystic fibrosis (CF) airway epithelia, and is being investigated as an inhaled treatment for CF. The Cl(-) secretory response is mediated via a non-CFTR pathway, and the driving force for Cl(-) secretion is enhanced by the effect of P2Y(2) activation to also inhibit epithelial Na(+) transport. Denufosol is metabolically more stable and better tolerated, and may enhance mucociliary clearance for a longer period of time than previously investigated P2Y(2) agonists. The goal of this phase 1/phase 2 study was to assess the safety and tolerability of single and repeated doses of aerosolized denufosol in subjects with CF. The study was a double-blind, placebo-controlled, multicenter comparison of ascending single doses of denufosol (10, 20, 40, and 60 mg, administered by inhalation via the Pari LC Star nebulizer) vs. placebo (normal saline), followed by a comparison of twice-daily administration of the maximum tolerated dose (MTD) of denufosol or placebo for 5 days. Thirty-seven adult (18 years of age or older) and 24 pediatric (5-17 years of age) subjects with CF were evaluated in five cohorts. Subjects were randomized in a 3:1 ratio to receive either denufosol or placebo within each cohort. The percent of subjects experiencing adverse events was similar between the denufosol and placebo groups. The most common adverse event in subjects receiving denufosol was chest tightness in adult subjects (39%) and cough in pediatric subjects (56%). Three (7%) subjects receiving denufosol and one (7%) subject receiving placebo experienced a serious adverse event. Forced expiratory volume in 1 sec (FEV(1)) profiles following dosing were similar across treatment groups, with some acute, reversible decline seen in both groups, most notably in subjects with lower lung function at baseline. In conclusion, doses up to 60 mg of denufosol inhalation

  6. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    SciTech Connect

    Yeo, Seung-Gu; Oh, Jae Hwan; Kim, Dae Yong; Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun; Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Nam, Taek-Keun

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  7. A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)

    PubMed Central

    Hutterer, Markus; Nowosielski, Martha; Haybaeck, Johannes; Embacher, Sabine; Stockhammer, Florian; Gotwald, Thaddäus; Holzner, Bernhard; Capper, David; Preusser, Matthias; Marosi, Christine; Oberndorfer, Stefan; Moik, Martin; Buchroithner, Johanna; Seiz, Marcel; Tuettenberg, Jochen; Herrlinger, Ulrich; Wick, Antje; Vajkoczy, Peter; Stockhammer, Günther

    2014-01-01

    Background Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing. Methods This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules. Results Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4–41.4 mo) and a median OS of 46.9 months (range, 21.2–49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity. Conclusion Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov Identifier: NCT00535379. PMID:24311637

  8. Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Investigate the Immunogenicity and Safety of a West Nile Virus Vaccine in Healthy Adults

    PubMed Central

    Biedenbender, Rex; Bevilacqua, Joan; Gregg, Anne M.; Watson, Mike

    2011-01-01

    Background. ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus. This Phase II, randomized, double-blind, placebo–controlled, multicenter study assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine. Methods. The 2-part study included adults in general good health. In part 1, subjects aged 18–40 years were randomized to 1 of 4 treatment groups: ChimeriVax–WN02 3.7- × -105 plaque-forming units (PFU), 3.7 × 104 PFU, 3.7 × 103 PFU, or placebo. In part 2, subjects aged 41–64 and ≥65 years were randomized to receive ChimeriVax-WN02 3.7 × 105 PFU or placebo. Results. In both part 1 and part 2, seroconversion was achieved at day 28 by >96% of subjects in active treatment groups. In part 1, neutralizing antibody titers at day 28 were higher and viremia levels lower with the highest dose, whereas the adverse event profile was similar between the dose groups. In part 2, antibody titers and viremia levels were higher in subjects aged ≥65 years, and more subjects in the 41–64 years cohort experienced adverse events. Conclusions. The ChimeriVax-WN02 vaccine was highly immunogenic in younger adults and the elderly, and it was well tolerated at all dose levels and in all age groups investigated. Clinical Trials.gov identifier: NCT00442169. PMID:21148499

  9. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    SciTech Connect

    Toledano, Alain H. . E-mail: alain.toledano@gmail.com; Bollet, Marc A.; Fourquet, Alain; Azria, David; Gligorov, Joseph; Garaud, Pascal; Serin, Daniel; Bosset, Jean-Francois; Miny-Buffet, Joelle; Favre, Anne; Le Foch, Olivier; Calais, Gilles

    2007-05-01

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair ({kappa} = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.

  10. Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer.

    PubMed

    Lee, Keun Seok; Chung, Hyun Cheol; Im, Seock Ah; Park, Yeon Hee; Kim, Chul Soo; Kim, Sung-Bae; Rha, Sun Young; Lee, Min Young; Ro, Jungsil

    2008-03-01

    Genexol-PM is a novel Cremophor EL-free polymeric micelle formulation of paclitaxel. This single arm, multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM in patients with histologically confirmed metastatic breast cancer (MBC). Forty-one women received Genexol-PM by intravenous infusion at 300 mg/m2 over 3 h every 3 weeks without premedication until disease progression or intolerability. A total of 331 chemotherapy cycles were administered, with a median of 8 cycles per patient (range, 1-16). Overall response rate was 58.5% (95% CI: 43.5-72.3) with 5 complete responses and 19 partial responses. Thirty-seven patients who received Genexol-PM as a first-line therapy for their metastatic disease showed a response rate of 59.5% (95% CI: 43.5-73.7), and two responses were reported in four patients treated in the second-line setting for their metastatic disease. The median time to progression (TTP) for all patients was 9.0 months (range, 1.0-17.0+ months). Grade 3 non-hematologic toxicities included sensory peripheral neuropathy (51.2%), and myalgia (2.4%). Eight patients (19.5%) experienced hypersensitivity reactions, with grade 3 in two patients. Hematologic toxicities were grade 3 and 4 neutropenia (51.2 and 17.1%, respectively), and grade 1 and 2 thrombocytopenia (22.0%). Notably, no febrile neutropenia was observed. Genexol-PM appears a promising new paclitaxel in view of significant efficacies. Further trials with different dosing schedules, durations of delivery, or in combination with other drugs are warranted.

  11. Decreased nonrelapse mortality after unrelated cord blood transplantation for acute myeloid leukemia using reduced-intensity conditioning: a prospective phase II multicenter trial.

    PubMed

    Rio, Bernard; Chevret, Sylvie; Vigouroux, Stéphane; Chevallier, Patrice; Fürst, Sabine; Sirvent, Anne; Bay, Jacques-Olivier; Socié, Gérard; Ceballos, Patrice; Huynh, Anne; Cornillon, Jérôme; Françoise, Sylvie; Legrand, Faezeh; Yakoub-Agha, Ibrahim; Michel, Gérard; Maillard, Natacha; Margueritte, Geneviève; Maury, Sébastien; Uzunov, Madalina; Bulabois, Claude Eric; Michallet, Mauricette; Clement, Laurence; Dauriac, Charles; Bilger, Karin; Gluckman, Eliane; Ruggeri, Annalisa; Buzyn, Agnès; Nguyen, Stéphanie; Simon, Tabassome; Milpied, Nöel; Rocha, Vanderson

    2015-03-01

    A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).

  12. Phase II, randomized, multicenter, double-blind, placebo-controlled trial of a polyclonal anti-Staphylococcus aureus capsular polysaccharide immune globulin in treatment of Staphylococcus aureus bacteremia.

    PubMed

    Rupp, Mark E; Holley, H Preston; Lutz, Jon; Dicpinigaitis, Peter V; Woods, Christopher W; Levine, Donald P; Veney, Naomi; Fowler, Vance G

    2007-12-01

    New treatment modalities are needed for the treatment of infections due to multidrug-resistant Staphylococcus aureus. S. aureus capsular polysaccharide immune globulin (Altastaph) is a polyclonal immune globulin preparation that is being developed as adjunctive therapy for persons with S. aureus infections complicated by bacteremia. In a phase II, multicenter, randomized, double-blind, placebo-controlled trial, 40 subjects with documented S. aureus bacteremia received standard therapy plus either Altastaph at 200 mg/kg of body weight in each of two infusions 24 h apart or placebo. During the 42-day observation period, antibody pharmacokinetics and safety were the primary characteristics studied. Information regarding the resolution of bacteremia and fever was also analyzed. Anti-type-5 and anti-type-8 capsular antibody levels peaked after the second infusion at 550 mug/ml and 419 mug/ml, respectively, and remained above 100 mug/ml at day 28. A total of 316 adverse events were noted in 39 of 40 subjects. Infusion-related adverse events in Altastaph recipients were infrequent and similar to those among recipients of commercial intravenously administered immunoglobulin G products. Five of 21 (23%) subjects in the Altastaph group died, whereas 2 of 18 (11%) subjects in the placebo group died (P = 0.42). Compared to the control patients, the Altastaph recipients had a shorter median time to the resolution of fever (2 days and 7 days, respectively; P = 0.09) and a shorter length of hospital stay (9 days and 14 days, respectively; P = 0.03). However, these findings are exploratory, and there were few differences in the other variables measured. High levels of opsonizing antibodies were maintained for the initial 4 weeks. Although the study was not powered to show efficacy, these preliminary findings and safety profile suggest that Altastaph may be an effective adjunct to antibiotics and warrants further investigation (ClinicalTrials.gov number NCT00063089).

  13. Preoperative Chemotherapy in Patients With Intermediate-Risk Rectal Adenocarcinoma Selected by High-Resolution Magnetic Resonance Imaging: The GEMCAD 0801 Phase II Multicenter Trial

    PubMed Central

    Brown, Gina; Estevan, Rafael; Salud, Antonieta; Montagut, Clara; Maurel, Joan; Safont, Maria Jose; Aparicio, Jorge; Feliu, Jaime; Vera, Ruth; Alonso, Vicente; Gallego, Javier; Martin, Marta; Pera, Miguel; Sierra, Enrique; Serra, Javier; Delgado, Salvadora; Roig, Jose V.; Santos, Jesus; Pericay, Carles

    2014-01-01

    Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. Methods. We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). Results. On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%–89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9–33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%–85%), and the 2-year local relapse rate was 2% (95% CI: 0%–11%). Conclusion. In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials. PMID:25209376

  14. Phase II, multicenter, open-label, randomized study of YM155 plus docetaxel as first-line treatment in patients with HER2-negative metastatic breast cancer.

    PubMed

    Clemens, Michael R; Gladkov, Oleg A; Gartner, Elaina; Vladimirov, Vladimir; Crown, John; Steinberg, Joyce; Jie, Fei; Keating, Anne

    2015-01-01

    The objective of this study was to assess the efficacy and tolerability of YM155, a survivin suppressor, in combination with docetaxel, compared with docetaxel alone in patients with HER2-negative metastatic breast cancer. This phase II, multicenter, open-label, 2-arm study randomized patients (≥18 years) with histologically or cytologically confirmed stage IV HER2-negative metastatic breast cancer and ≥1 measurable lesion, to receive docetaxel alone or docetaxel plus YM155. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR), biomarker assessment, and analysis of circulating tumor cells. Patients were women diagnosed with HER2-negative breast cancer; most had received prior drug therapies. The median PFS was 8.4 months with YM155 plus docetaxel (n = 50) and 10.5 months with docetaxel alone (n = 51; HR 1.53; 95 % CI 0.83, 2.83; P = 0.176). No statistically significant differences were observed for secondary endpoints, although slightly greater OS (630 vs 601 days; P = 0.768), CBR (84.3 vs 82.0 %; P = 0.855), DOR, and TTR were observed with docetaxel alone compared with YM155 plus docetaxel, whereas ORR was similar (25.5 vs 26.0). The most common TEAEs observed with YM155 plus docetaxel compared with docetaxel alone were neutropenia (83.3 vs 84.3 %), alopecia (62.5 vs 52.9 %), fatigue (50 vs 41.2 %), and nausea (37.5 vs 41.2 %). Although YM155 is a novel drug that suppresses survivin, YM155 plus docetaxel exhibited no statistically significant differences in endpoints compared with docetaxel alone. The combination regimen was well tolerated.

  15. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial

    PubMed Central

    von Mehren, Margaret; Jones, Robin L.; Hensley, Martee L.; Schuetze, Scott M.; Staddon, Arthur; Milhem, Mohammed; Elias, Anthony; Ganjoo, Kristen; Tawbi, Hussein; Van Tine, Brian A.; Spira, Alexander; Dean, Andrew; Khokhar, Nushmia Z.; Park, Youn Choi; Knoblauch, Roland E.; Parekh, Trilok V.; Maki, Robert G.; Patel, Shreyaskumar R.

    2016-01-01

    Purpose This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients and Methods Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control—progression-free survival (PFS), time to progression, objective response rate, and duration of response—as well as safety and patient-reported symptom scoring. Results A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Conclusion Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. PMID:26371143

  16. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

    PubMed

    Chen, Robert; Palmer, Joycelynne M; Martin, Peter; Tsai, Nicole; Kim, Young; Chen, Bihong T; Popplewell, Leslie; Siddiqi, Tanya; Thomas, Sandra H; Mott, Michelle; Sahebi, Firoozeh; Armenian, Saro; Leonard, John; Nademanee, Auayporn; Forman, Stephen J

    2015-12-01

    This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

  17. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

    PubMed

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

  18. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

    PubMed Central

    2011-01-01

    Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and

  19. A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 28-Day, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    PubMed Central

    Furey, Sandy A.; Hull, Steven G.; Leibowitz, Mark T.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objective: To evaluate multiple doses of gabapentin 250 mg on polysomnography (PSG) and participant-reported sleep assessments in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 250 mg (n = 128) or placebo (n = 128). On Days 1 and 28, participants received medication 30 min before bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, a post sleep questionnaire, and the Karolinska Sleep Diary. Next-day residual effects and tolerability were evaluated. On Days 2-27, participants took medication at home 30 min before their habitual bedtime. Results: Treatment-group demographics were comparable. Gabapentin resulted in significantly less PSG wake after sleep onset (WASO) compared with placebo on Day 1 (primary endpoint, mean: 107.0 versus 149.1 min, p ≤ 0.001) and Day 28 (113.6 versus 152.3 min, p = 0.002), and significantly greater total sleep time (TST; Day 1: 347.6 versus 283.9 min; Day 28: 335.3 versus 289.1 min) (p ≤ 0.001). Participant-reported WASO and TST also showed significant treatment effects on both days. Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo. During home use, gabapentin resulted in significantly less participant-reported WASO and higher ratings of sleep quality. Gabapentin was well tolerated (most common adverse events: headache, somnolence) with no evidence of next-day impairment. Conclusion: Gabapentin 250 mg resulted in greater PSG and participant-reported sleep duration following a 5-h phase advance on Day 1 and Day 28 of use without evidence of next-day impairment, and greater sleep duration during at-home use. Citation: Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014

  20. A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    PubMed Central

    Rosenberg, Russell P.; Hull, Steven G.; Lankford, D. Alan; Mayleben, David W.; Seiden, David J.; Furey, Sandy A.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objectives: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. Results: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (< 5%). Conclusion: Participants with occasional disturbed sleep treated with gabapentin showed significantly longer sleep duration and greater depth (versus placebo) in response to a phase advance manipulation known to disrupt sleep maintenance. Citation: Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, Jayawardena S, Roth T. A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient

  1. A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

    PubMed

    Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko

    2017-01-01

    Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

  2. High intensity focused ultrasound (HIFU) treatment of BPH: results of a multi-center phase III study

    NASA Astrophysics Data System (ADS)

    Sanghvi, N.; Gardner, T.; Koch, M.; Bihrle, R.; Foster, R.; Resnick, M.; Seftel, A.; Grunberger, I.; Stiedle, C.; Corchan, J.

    2003-04-01

    The five centers phase III trial was to show that HIFU can treat prostate tissue thermally for symptomatic relief of BPH and improve flow rates. At five sites, 68 BPH patients were treated with the Sonablate device (Focus Surgery, Inc. Indianapolis, IN). A urethral Foley catheter was inserted into the urethra to aid in positioning and was kept in-situ during the treatment. A cooling device was used to cool the rectal wall. The patients returned home within a few hours after the procedure. The Foley catheter was kept electively to avoid any incidence of acute urinary retention following the therapy. The catheter was removed after 4-5 days. The average treatment time was 38 minutes. The patients were treated without pain, blood loss or complications. At 90 days post treatment, average Qmax and AUA Symptom Scores improved from 8.7 ml/s to 12.66 ml/s (48%) and 23.06 to 11.62 (52%), respectively. Significant prostate tissue changes took place before and after the treatment. 80% of the patients had cavity formation at the site of treatment at the bladder neck and prostate. Nonsurgical HIFU therapy is safe and effective for providing symptomatic relief of BPH symptoms and the treatment can be performed as an outpatient procedure.

  3. Difluprednate 0.05% Versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: A Phase III, Multicenter, Randomized Study

    PubMed Central

    Sheppard, John D.; Toyos, Melissa M.; Kempen, John H.; Kaur, Paramjit; Foster, C. Stephen

    2014-01-01

    Purpose. Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. Methods. This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. Results. At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (−2.2 vs. −2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate–treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate–treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. Conclusions. Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.) PMID:24677110

  4. A multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma.

    PubMed

    Maruyama, Dai; Hatake, Kiyohiko; Kinoshita, Tomohiro; Fukuhara, Noriko; Choi, Ilseung; Taniwaki, Masafumi; Ando, Kiyoshi; Terui, Yasuhito; Higuchi, Yusuke; Onishi, Yasushi; Abe, Yasunobu; Kobayashi, Tsutomu; Shirasugi, Yukari; Tobinai, Kensei

    2017-03-07

    Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was started in March 2015. We report data obtained at a cutoff of March 16, 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow-up were 7.0 (1.4-10.6) months and 9.8 (6.0-11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4%-96.0%; 13/16 patients), with complete remission and partial remission in four and nine patients, respectively. The overall survival (OS) and progression-free survival (PFS) rates at 6 months were 100% and 60.0% (95% CI: 31.8%-79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AEs) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%), and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AEs, but most AEs were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin. This article is protected by copyright. All rights reserved.

  5. Immunochemotherapy with interleukin-2, interferon- α and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study

    PubMed Central

    Herpen, C M L van; Jansen, R L H; Kruit, W H J; Hoekman, K; Groenewegen, G; Osanto, S; Mulder, P H M De

    2000-01-01

    In patients with metastatic renal cell carcinoma response rates of 7–26% have been achieved with immunotherapy. A high response rate of 48% in 35 patients has been reported for treatment with the combination of interferon-α (IFN-α), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993 a) Eur J Cancer29A: S6–8). We conducted a multicentre phase II study to confirm these results. Metastatic renal cell carcinoma patients were treated as outpatients with an 8-week treatment cycle. Recombinant human IL-2 20 MU m−2was administered subcutaneously (s.c.) three times a week (t.i.w) in weeks 1 and 4 and 5 MU m−2t.i.w. in weeks 2 and 3. Recombinant human IFN-α 2a 6 MU m−2was administered s.c. once in weeks 1 and 4 and t.i.w. in weeks 2 and 3, and 9 MU m−2t.i.w. in weeks 5–8. 5-FU (750 mg m−2) was given as a bolus injection intravenous once a week in weeks 5–8. The treatment cycle was repeated once in case of response or minor response. Fifty-two patients entered the study. All had undergone a nephrectomy and had progressive metastatic disease. The median WHO-performance status was 1, the median number of metastatic sites was 2 (range 1–5) and the median time between the diagnosis of the primary tumour and the start of treatment was 12.9 months (range 1–153). Among the 51 patients, including four patients with early progressive disease, who were evaluable for response, the response rate was 11.8% (95% confidence interval (CI) 2.9–20.7%), with no complete responses. Median duration of response was 8.3 (range 3.8–22.4+) months. Median survival was 16.5 (range 1.8–30.5+) months. Grade 3/4 toxicity (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 (37.5%) of the patients in cycle 2. It consisted mainly of anorexia, fatigue, nausea, fever and leucocytopenia. We cannot confirm the high response rate in patients with metastatic renal cell carcinoma treated with the combination of IFN-α, IL-2 and 5-FU, as described

  6. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study.

    PubMed

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-06-01

    Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy.IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint).The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3 intestinal BD

  7. Paclitaxel injection concentrate for nanodispersion versus nab-paclitaxel in women with metastatic breast cancer: a multicenter, randomized, comparative phase II/III study.

    PubMed

    Jain, Minish M; Gupte, Smita U; Patil, Shekhar G; Pathak, Anand B; Deshmukh, Chetan D; Bhatt, Niraj; Haritha, Chiramana; Govind Babu, K; Bondarde, Shailesh A; Digumarti, Raghunadharao; Bajpai, Jyoti; Kumar, Ravi; Bakshi, Ashish V; Bhattacharya, Gouri Sankar; Patil, Poonam; Subramanian, Sundaram; Vaid, Ashok K; Desai, Chirag J; Khopade, Ajay; Chimote, Geetanjali; Bapsy, Poonamalle P; Bhowmik, Shravanti

    2016-02-01

    Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2

  8. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study

    PubMed Central

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-01-01

    Abstract Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy. IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint). The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3

  9. A Prospective Phase 2 Multicenter Study for the Efficacy of Radiation Therapy Following Incomplete Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

    SciTech Connect

    Choi, Chihwan; Koom, Woong Sub; Kim, Tae Hyun; Yoon, Sang Min; Kim, Jin Hee; Lee, Hyung-Sik; Nam, Taek-Keun; Seong, Jinsil

    2014-12-01

    Purpose: The purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC). Methods and Materials: The study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACE in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT. Results: Between August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS (P=.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure. Conclusions: Early 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.

  10. Bolting multicenter solutions

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Bossard, Guillaume; Katmadas, Stefanos; Turton, David

    2017-01-01

    We introduce a solvable system of equations that describes non-extremal multicenter solutions to six-dimensional ungauged supergravity coupled to tensor multiplets. The system involves a set of functions on a three-dimensional base metric. We obtain a family of non-extremal axisymmetric solutions that generalize the known multicenter extremal solutions, using a particular base metric that introduces a bolt. We analyze the conditions for regularity, and in doing so we show that this family does not include solutions that contain an extremal black hole and a smooth bolt. We determine the constraints that are necessary to obtain smooth horizonless solutions involving a bolt and an arbitrary number of Gibbons-Hawking centers.

  11. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

    PubMed Central

    Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

    2016-01-01

    Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

  12. Treatment of limited stage follicular lymphoma with Rituximab immunotherapy and involved field radiotherapy in a prospective multicenter Phase II trial-MIR trial

    PubMed Central

    2011-01-01

    Background The optimal treatment of early stage follicular Lymphoma is a matter of debate. Radiation therapy has frequently been applied with a curative approach beside watchful waiting. Involved field, extended field and total nodal radiation techniques are used in various protocols, but the optimal radiation field still has to be defined. Follicular lymphoma is characterized by stable expression of the CD20 antigen on the tumour cells surface. The anti CD20 antibody Rituximab (Mabthera®) has shown to be effective in systemic therapy of FL in primary treatment, relapse and maintenance therapy. Methods/design The MIR (Mabthera® and Involved field Radiation) study is a prospective multicenter trial combining systemic treatment with the anti CD20 antibody Rituximab (Mabthera®) in combination with involved field radiotherapy (30 - 40 Gy). This trial aims at testing the combination's efficacy and safety with an accrual of 85 patients. Primary endpoint of the study is progression free survival. Secondary endpoints are response rate to Rituximab, complete remission rate at week 18, relapse rate, relapse pattern, relapse free survival, overall survival, toxicity and quality of life. Discussion The trial evaluates the efficacy of Rituximab to prevent out-filed recurrences in early stage nodal follicular lymphoma and the safety of the combination of Rituximab and involved field radiotherapy. It also might show additional risk factors for a later recurrence (e.g. remission state after Rituximab only). Trial Registration ClinicalTrials (NCT): NCT00509184 PMID:21352561

  13. Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra®, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

    PubMed Central

    Raza, Azra; Galili, Naomi; Callander, Natalie; Ochoa, Leonel; Piro, Lawrence; Emanuel, Peter; Williams, Stephanie; Burris, Howard; Faderl, Stefan; Estrov, Zeev; Curtin, Peter; Larson, Richard A; Keck, James G; Jones, Marsha; Meng, Lisa; Brown, Gail L

    2009-01-01

    Background Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m2) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle. Results 54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed. Conclusion Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development. Trial Registration Clinicaltrials.gov: NCT00035867 PMID:19439093

  14. A Multicenter, Single-Blind, Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of a Cell-Mediated Gene Therapy in Degenerative Knee Arthritis Patients.

    PubMed

    Ha, Chul-Won; Cho, Jung Jong; Elmallah, Randa K; Cherian, Jeffrey J; Kim, Tae Won; Lee, Myung-Chul; Mont, Michael A

    2015-06-01

    Osteoarthritis leads to articular cartilage wear, and newer therapies are aimed at slowing this degeneration. Growth factors and cytokines influence cartilage formation, and researchers are studying their use on cartilage regeneration in osteoarthritis. One method uses genetically engineered cells to deliver growth factors to damaged cartilage. This technique utilizes transforming growth factor-β proteins in modified chondrocytes to stimulate cartilage growth via an intra-articular injection. We evaluated the efficacy and outcomes of this injection on patients who had International Cartilage Repair Society grade 4 knee osteoarthritis. We evaluated 27 patients (6 men, 21 women) who had late-stage knee osteoarthritis. Patients were randomized to receive genetically engineered chondrocytes doses of 6×10(6) cells (group 1) or 1.8×10(7) cells (group 2) at a 1:1 ratio. Primary endpoints were subjective and functional evaluations, assessed by the International Knee Documentation Committee (IKDC) score. Secondary endpoints were pain severity and physical function, using the Western Ontario and McMaster osteoarthritis (WOMAC) index and the 100 mm visual analog scale (VAS). Patients were followed at 2, 4, 12, and 24 weeks postinjection. Both groups had significant improvements in outcomes. Scores improved at 12 and 24 weeks from baseline in IKDC (+10 and +14 points in group 1; +11 and +13 points in group 2), WOMAC (-12 and -13 points in group 1; -10 and -12 points in group 2), and VAS (-19 and -24 points in group 1; -20 and -20 in group 2) scores. Additionally, there were no serious adverse events, and no significant difference in adverse event incidence between the groups. Both groups expressed a mean improvement in pain, function, and physical ability following treatment injection. This modality appears to be a promising treatment for cartilage degeneration. However, further larger, multicenter, randomized studies are needed to truly evaluate the efficacy of this

  15. Multicenter, Single-Arm, Phase IV Study of Combined Aspirin and High-Dose “IVIG-SN” Therapy for Pediatric Patients with Kawasaki Disease

    PubMed Central

    Yoon, Kyung Lim; Lee, Hae Yong; Yu, Jeong Jin; Lee, Jae Young; Han, Mi Young; Kim, Ki Yong

    2017-01-01

    Background and Objectives Intravenous immunoglobulin-SN (IVIG-SN) is a new human immunoglobulin product. Its safety is ensured by pathogen-elimination steps comprising solvent/detergent treatment and a nanofiltration process. This multicenter clinical study was designed to evaluate the efficacy and safety of combined aspirin and high-dose IVIG-SN therapy in pediatric patients with Kawasaki disease (KD). Subjects and Methods We evaluated coronary artery lesions (CALs) at 2 and 7 weeks after administering IVIG-SN; total fever duration; and variations in erythrocyte sedimentation rate, N-terminal pro B-type natriuretic peptide or B-type natriuretic peptide, and creatine kinase-myocardial band level before and after treatment with IVIG-SN (2 g/kg). Adverse events were monitored. Results Forty-five patients were enrolled, three of whom were excluded according to the exclusion criteria; the other 42 completed the study. The male:female ratio was 0.91:1, and the mean age was 29.11±17.23 months. The mean fever duration before IVIG-SN treatment was 6.45±1.30 days. Although most patients had complete KD (40 patients, 90.91%), four had atypical KD (9.09%). After IVIG-SN treatment, one patient (2.38%) had CALs, which was significantly lower than the incidence reported previously (15%) (p=0.022), but not significantly different from recent data (5%). There were no serious adverse events, though 28 patients (63.64%) had mild adverse events. Three adverse drug reactions occurred in 2 patients (eczema, anemia, and increased eosinophil count), all of which were transient. Conclusion IVIG-SN treatment in patients with KD was safe and effective. PMID:28382076

  16. Elliptic genera from multi-centers

    NASA Astrophysics Data System (ADS)

    Gaddam, Nava

    2016-05-01

    I show how elliptic genera for various Calabi-Yau threefolds may be understood from supergravity localization using the quantization of the phase space of certain multi-center configurations. I present a simple procedure that allows for the enumeration of all multi-center configurations contributing to the polar sector of the elliptic genera — explicitly verifying this in the cases of the quintic in {P} 4, the sextic in {W}{P} (2,1,1,1,1), the octic in {W}{P} (4,1,1,1,1) and the dectic in {W}{P} (5,2,1,1,1). With an input of the corresponding `single-center' indices (Donaldson-Thomas invariants), the polar terms have been known to determine the elliptic genera completely. I argue that this multi-center approach to the low-lying spectrum of the elliptic genera is a stepping stone towards an understanding of the exact microscopic states that contribute to supersymmetric single center black hole entropy in {N} = 2 supergravity.

  17. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial

    PubMed Central

    Tang, Chunyuan; Wu, Fang; Wang, Rensheng; Lu, Heming; Li, Guisheng; Liu, Meilian; Zhu, Haisheng; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Metastasis is the major cause of death in NPC patients. Concurrent chemoradiotherapy (CCRT) has been accepted as standard in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, induction chemotherapy (IC) also has benefits in this disease, especially in the patients with certain high-risk factors such as bulky and/or extensive nodal disease. It has been presented that adding IC to CCRT might be a reasonable approach and need more work to confirm. The optimal chemotherapeutic regimen combined with radiotherapy has not been determined so far. It is important to explore high effective and low toxic chemotherapy for the patients. In the multicenter prospective study, 223 patients with locoregionally advanced untreated NPC were randomized into experimental group and control group. The patients received two cycles of induction chemotherapy (IC) with docetaxel (DOC) plus nedaplatin (NDP) in experimental group every 3 weeks, followed by IMRT concurrent with weekly NDP for six cycles, and NDP was replaced by cisplatin (CDDP) in control group. More patients in experimental group could receive full courses of IC and concurrent chemoradiotherapy (CCRT) (P=0.013). There was no significant difference between the two groups in the percentage of reduction of GTVnx and GTVnd after IC (P=0.207 and P=0.107) and CR rate three months after completion of chemoradiotherapy (P=0.565 and P=0.738). With a mean follow-up of 35.1 months, no statistically significant difference in the 3-year OS, LRFS, RRFS, DMFS, and PFS was found. During IC, more patients suffered vomiting in control group (P=0.001). During CCRT, grade 3/4 neutropenia/thrombocytopenia were more common in experimental group (P=0.028 and P=0.035); whereas, severe anemia and vomiting were more common in control group (P=0.0001 and P=0.023). In conclusions, patients with locoregionally advanced NPC showed good

  18. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma.

    PubMed

    Hauschild, Axel; Weichenthal, Michael; Rass, Knuth; Linse, Ruthild; Ulrich, Jens; Stadler, Rudolf; Volkenandt, Matthias; Grabbe, Stephan; Proske, Ulrike; Schadendorf, Dirk; Brockmeyer, Norbert; Vogt, Thomas; Rompel, Rainer; Kaufmann, Roland; Kaatz, Martin; Näher, Helmut; Mohr, Peter; Eigentler, Thomas; Livingstone, Elisabeth; Garbe, Claus

    2009-07-20

    PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.

  19. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.

  20. Randomized, Double-Blind, Multicenter Phase 2 Study Comparing the Efficacy and Safety of Oral Solithromycin (CEM-101) to Those of Oral Levofloxacin in the Treatment of Patients with Community-Acquired Bacterial Pneumonia

    PubMed Central

    Oldach, David; Clark, Kay; Schranz, Jennifer; Das, Anita; Craft, J Carl; Scott, Drusilla; Jamieson, Brian D.

    2013-01-01

    Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.6% for solithromycin versus 86.6% for levofloxacin) and microbiological-intent-to-treat (micro-ITT) (77.8% for solithromycin versus 71.4% for levofloxacin) populations. Early response success rates at day 3, defined as improvement in at least two cardinal symptoms of pneumonia, were also comparable (72.3% for solithromycin versus 71.6% for levofloxacin). More patients treated with levofloxacin than with solithromycin experienced treatment-emergent adverse events (TEAEs) during the study (45.6% versus 29.7%). The majority of TEAEs were mild or moderate gastrointestinal symptoms and included nausea (1.6% for solithromycin; 10.3% for levofloxacin), diarrhea (7.8% for solithromycin; 5.9% for levofloxacin), and vomiting (0% for solithromycin; 4.4% for levofloxacin). Six patients, all of whom received levofloxacin, discontinued the study drug due to an adverse event. Solithromycin demonstrated comparable efficacy and favorable safety relative to levofloxacin. These findings support a phase 3 study of solithromycin for the treatment of CABP. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168713.) PMID:23507282

  1. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

    SciTech Connect

    Bensadoun, Rene-Jean . E-mail: rene-jean.bensadoun@nice.fnclcc.fr; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

    2006-03-15

    Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.

  2. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis

    PubMed Central

    Verstovsek, S; Talpaz, M; Ritchie, E; Wadleigh, M; Odenike, O; Jamieson, C; Stein, B; Uno, T; Mesa, R A

    2017-01-01

    NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK–signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1–2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion. PMID:27479177

  3. A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

    PubMed Central

    2013-01-01

    Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was

  4. A Multicenter, Open Labeled, Randomized, Phase III Study Comparing Lopinavir/Ritonavir Plus Atazanavir to Lopinavir/Ritonavir Plus Zidovudine and Lamivudine in Naive HIV-1-Infected Patients: 48-Week Analysis of the LORAN Trial

    PubMed Central

    Ulbricht, K.U; Behrens, G.M; Stoll, M; Salzberger, B; Jessen, H; Jessen, A.B; Kuhlmann, B; Heiken, H; Trein, A; Schmidt, R.E

    2011-01-01

    Objective: The primary aim of the study was to compare the metabolic side effects of a nucleoside analogue-containing regimen with a nucleoside analogue-sparing double protease inhibitor regimen. A secondary goal was to test for efficacy of a double-PI regimen. Design: Multicenter, randomized, open-label, phase III clinical trial. Subjects: Adult HIV-1-infected individuals naïve to antiretroviral therapy with viral load above 400 HIV-RNA copies/ml were randomized (1:1) to either 400 mg lopinavir /100 mg ritonavir (LPV/r) BID plus 150 mg lamivudine/300 mg zidovudine (CBV) BID versus LPV/r BID plus 300 mg atazanavir (ATV) QD. Main outcome measure was the virologic failure in both groups, defined as viral load ≥50 copies/ml at week 48. Results: In the CBV/LPV/r-arm, 29 out of 35 patients [(83%; 95% confidence interval (CI) 66.9-92.2%] and 18 out of 40 patients (45%; 95% CI 29.7-61.5%) in the ATV/LPV/r-arm had a HIV-RNA level <50 copies/ml at week 48. The intent-to-treat analysis revealed inferior virologic response in the ATV/LPV/r arm (Chi-Q and Fisher´s Exact Test p<0.001) and resulted in premature termination of the trial. Eleven patients in the ATV/LPV/r-arm discontinued therapy because of virological failure. These failures mostly presented with low level replication (<1,000 copies/ml). Increases in CD4 cell counts was significantly more rapid in the ATV/LPV/r arm (p=0.02), but comparable at week 48. Conclusions: ATV/LPV/r had less virologic efficacy than the conventional RTI-based regimen and resulted in a high virological failure rate with low level replication. PMID:21643422

  5. Efficacy and Safety of Gemcitabine (G), Carboplatin (C), Dexamethasone (D), and Rituximab (R) in Patients with Relapsed/Refractory Lymphoma: A Prospective Multi-center Phase II Study of by the Puget Sound Oncology Consortium (PSOC)

    PubMed Central

    Gopal, Ajay K.; Press, Oliver W.; Shustov, Andrei R.; Petersdorf, Stephen H.; Gooley, Ted A.; Daniels, Jasmine T.; Garrison, Mitchell A.; Gjerset, George F.; Lonergan, Matthew; Murphy, Anne E.; Smith, Julie C.; Pagel, John M.

    2010-01-01

    We conducted a multi-center phase II trial of gemcitabine (G), carboplatin (C), dexamethasone (D), and rituximab (R) in order to examine its safety and efficacy as an outpatient salvage regimen for lymphoma. Fifty-one patients received 2–4 21-day cycles of G (1000mg/m2, days 1 and 8), C (AUC=5, day 1), D (40mg daily days 1–4), and R (375mg/m2, day 8 for CD20 positive disease) and were evaluable for response. Characteristics included: median age 58y (19–79y), stage III/IV 88%, elevated LDH 33%, median prior therapies 2, prior stem cell transplant 12%, chemoresistant 62%, median prior remission duration 2.5 months. The overall and complete response rates were 67% (95% confidence interval [CI], 54–80%) and 31% (95% CI 19–44%), respectively, with activity seen in a broad variety of histologies. Responses occurred in 16 of 17 (94%, 95% CI 83–100%) transplant eligible patients and 15 of 28 (54%, 95% CI 34–71%) with chemoresistant disease. The median CD34 yield in patients attempting peripheral blood stem cell (PBSC) collection following this regimen was 10.9 × 106 CD34+ cells/kg (range, 5.0 – 24.1 × 106). Hematologic toxicity was common but febrile neutropenia (2.5%) and grade 4 non-hematologic adverse events (n=2) were rare with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma and successfully mobilizes PBSC. PMID:20578815

  6. A phase III single arm, multicenter, open-label study to assess the immunogenicity and tolerability of a pentavalent DTwP–HepB–Hib vaccine in indian infants

    PubMed Central

    Eregowda, Adarsh; Lalwani, Sanjay; Chatterjee, Sukanta; Vakil, Hoshang; Ahmed, Khaleel; Costantini, Marco; Lattanzi, Maria

    2013-01-01

    Compliance with recommended vaccinations for Indian infants is facilitated by using combination vaccines to minimize the number of required injections. The ready-to-use, preservative free, fully-liquid combination DTwP–HepB–Hib vaccine, Quinvaxem®, offers convenience of administering five important vaccine antigens to infants in a single injection. This phase III, single-arm, multicenter study was designed to assess immunogenicity and safety of three doses of Quinvaxem® to Indian infants administered at 6, 10, and 14 weeks of age. Blood samples were taken prior to the first dose and at one month post last vaccination. Infants were observed clinically for any reaction approximately 30 min following each vaccination, and parents completed subject diaries for solicited local, systemic and any adverse events (AEs) following over a 5 d period. DTwP–HepB–Hib vaccine elicited strong immune responses that exceeded seroprotection/seroconversion thresholds against all vaccine antigens. At one month after third vaccination, percentages of infants achieving predefined protective antibody levels were 99% diphtheria; 100% tetanus; 98% Hepatitis B; 100% Hib short-term (≥ 0.15 µg/mL); 95% Hib long-term (≥ 1.0 µg/mL) protection; and relevant immune response was 99% for pertussis. The vaccine was well tolerated, with no vaccine-related serious AEs. Only one case of high fever (≥ 40°C) was reported. The most frequently reported reactions were mild to moderate tenderness and erythema. Frequencies of all AEs declined with subsequent vaccinations. This study demonstrated that this convenient, fully-liquid DTwP–HepB–Hib vaccine is highly immunogenic and has a acceptable safety profile for use in Indian infants. ClinicalTrials.gov Identifier: NCT01470287. Clinical Trials Registry of India Number: CTRI/2011/11/002118 PMID:23783081

  7. The Effect of Additional Training on Motor Outcomes at Discharge from Recovery Phase Rehabilitation Wards: A Survey from Multi-Center Stroke Data Bank in Japan

    PubMed Central

    Shiraishi, Nariaki; Suzuki, Yusuke; Matsumoto, Daisuke; Jeong, Seungwon; Sugiyama, Motoya; Kondo, Katsunori; Kuzuya, Masafumi

    2014-01-01

    Objectives The purpose of the present study was to examine the potential benefits of additional training in patients admitted to recovery phase rehabilitation ward using the data bank of post-stroke patient registry. Subjects and Methods Subjects were 2507 inpatients admitted to recovery phase rehabilitation wards between November 2004 and November 2010. Participants were retrospectively divided into four groups based upon chart review; patients who received no additional rehabilitation, patients who were added with self-initiated off hours training, patients who were added with off hours training by ward staff, patients who received both self-initiated training and training by ward staff. Parameters for assessing outcomes included length of stay, motor/cognitive subscales of functional independent measures (FIM) and motor benefit of FIM calculated by subtracting the score at admission from that at discharge. Results Participants were stratified into three groups depending on the motor FIM at admission (≦28, 29∼56, 57≦) for comparison. Regarding outcome variables, significant inter-group differences were observed in all items examined within the subgroup who scored 28 or less and between 29 and 56. Meanwhile no such trends were observed in the group who scored 57 or more compared with those who scored less. In a decision tree created based upon Exhaustive Chi-squared Automatic Interaction Detection method, variables chosen were the motor FIM at admission (the first node) additional training (the second node), the cognitive FIM at admission(the third node). Conclusions Overall the results suggest that additional training can compensate for the shortage of regular rehabilitation implemented in recovery phase rehabilitation ward, thus may contribute to improved outcomes assessed by motor FIM at discharge. PMID:24626224

  8. Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial

    PubMed Central

    Neely, E. Kirk; Kletter, Gad B.; Lewis, Katherine; Chitra, Surya; Terleckyj, Oksana; Eugster, Erica A.

    2015-01-01

    Context and Objective: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. Design: This was a phase 3, prospective, open-label study. Setting and Participants: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. Outcome Measures: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. Results: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. Conclusions: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP. PMID:25803268

  9. SHARE: a French multicenter phase III trial comparing accelerated partial irradiation versus standard or hypofractionated whole breast irradiation in breast cancer patients at low risk of local recurrence.

    PubMed

    Belkacemi, Yazid; Bourgier, Céline; Kramar, Andrew; Auzac, Guillaume; Dumas, Isabelle; Lacornerie, Thomas; Mége, Jean-Pierre; Mijonnet, Sylvie; Lemonnier, Jerôme; Lartigau, Eric

    2013-02-01

    The standard treatment for breast cancer patients at low risk of recurrence is based on conservative surgery followed by radiation therapy delivered to the whole breast. The accelerated partial breast irradiation (APBI) concept, developed more than 15 years ago, could be an option in selected patients. However, the ideal patient profile for APBI is still not clearly identified. Recent reports from the American Society for Radiation Oncology (ASTRO) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) have suggested selection criteria for "suitable patients" who could receive APBI outside of clinical trials. Currently, there are 6 ongoing phase III trials. All are characterized by a significant heterogeneity regarding inclusion criteria and stratification factors. The French UNICANCER trial (SHARE; ClinicalTrials.gov identifier NCT01247233) will randomize 2,800 patients in 3 arms: APBI (1 week) using 3-dimensional (3D) conformal radiotherapy, standard radiotherapy (6.5 weeks), and hypofractionated radiotherapy (3 weeks). In this article, we review the reported retrospective studies as well as older randomized trials. We will also describe the differences between the 6 ongoing phase III trials and the particularities of the French SHARE trial.

  10. A National Multicenter Phase 2 Study of Prostate-specific Antigen (PSA) Pox Virus Vaccine with Sequential Androgen Ablation Therapy in Patients with PSA Progression: ECOG 9802

    PubMed Central

    DiPaola, Robert S.; Chen, Yu-Hui; Bubley, Glenn J.; Stein, Mark N.; Hahn, Noah M.; Carducci, Michael A.; Lattime, Edmund C.; Gulley, James; Arlen, Philip M.; Butterfield, Lisa H.; Wilding, George

    2014-01-01

    Background E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. Objective To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Design, setting, and participants Patients had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Outcome measurements and statistical analysis Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. Results and limitations In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48–75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p = 0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57–87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. Conclusions A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients

  11. EXTRA-A Multicenter Phase II Study of Chemoradiation Using a 5 Day per Week Oral Regimen of Capecitabine and Intravenous Mitomycin C in Anal Cancer

    SciTech Connect

    Glynne-Jones, Rob Meadows, Helen; Wan, Susan; Gollins, Simon; Leslie, Martin; Levine, Ed; McDonald, Alec C.; Myint, Sun; Samuel, Les; Sebag-Montefiore, David

    2008-09-01

    Purpose: 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. Methods and Materials: Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m{sup 2}) on Day 1 and capecitabine on each RT treatment day in two divided doses (825 mg/m{sup 2} b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. Results: Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. Conclusions: Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.

  12. The effect of water fluoride concentration on dental caries and fluorosis in five Iran provinces: A multi-center two-phase study

    PubMed Central

    Ramezani, Gholamhossein; Valaie, Nasser; Rakhshan, Vahid

    2015-01-01

    Background: Water fluoride level is unknown in many regions of Iran. Besides, only few non-controlled studies world-wide have assessed the effect of water fluoride on dental fluorosis and caries. We aimed to measure the fluoride level of 76 water supplies in 54 cities and evaluate the effect of fluoride on dental caries and fluorosis in a large multi-project study. Materials and Methods: In the first phase (cross-sectional), fluoride levels of 76 water tanks in 54 cities/villages in five provinces of Iran were randomly evaluated in five subprojects. In the second phase (retrospective cohort), 1127 middle school children (563 cohort and 564 control subjects) in the high and low ends of fluoride concentration in each subproject were visited. Their decayed, missing and filled teeth (DMFT) and fluorosis states were assessed. The data were analyzed using Chi-square, Mann-Whitney U and independent-samples t-test (α = 0.05). Results: Mean fluoride level was 0.298 ± 0.340 mg/L in 54 cities/villages. Only eight water tanks had fluoride levels within the normal range and only one was higher than normal and the rest (67 tanks) were all at low levels. Overall, a significant association was observed between fluoride level and fluorosis. However, this was not the case in all areas, as in 2 of 5 provinces, the effect of fluoride on fluorosis was not confirmed. In 4 of the 5 areas studied, there was a significant link between fluoride level and DMFT. Conclusion: Extremely low fluoride levels in Iran cities are an alarming finding and need attention. Higher fluoride is likely to reduce dental caries while increasing fluorosis. This finding was not confirmed in all the areas studied. PMID:25709672

  13. A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barré Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS)

    PubMed Central

    Yamaguchi, Nobuko; Sato, Yasunori; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kohara, Nobuo; Hirata, Koichi; Nishiyama, Kazutoshi; Yabe, Ichiro; Kaida, Ken-Ichi; Suzuki, Norihiro; Nodera, Hiroyuki; Tsuji, Shoji; Koike, Haruki; Kira, Jun-Ichi; Hanaoka, Hideki; Kusunoki, Susumu; Kuwabara, Satoshi

    2016-01-01

    Background Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation. Objective This clinical trial aims to evaluate the efficacy and safety of eculizumab, a humanized monoclonal antibody directed against complement component 5, for treatment of GBS. Methods The Japanese Eculizumab Trial for GBS (JET-GBS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 33 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3-5) were randomized at a 2:1 ratio to receive either intravenous eculizumab (900 mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow-up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial. Results Enrollment for the trial began in August 2015. This trial is still ongoing. All participants have been enrolled, and follow-up will be completed in October 2016. Conclusions This study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients. ClinicalTrial UMIN Clinical Trials Registry UMIN

  14. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    PubMed

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m(-2) within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.

  15. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

    PubMed Central

    Pugliese, Mariateresa; Gallo, Marco; Brignardello, Enrico; Milla, Paola; Orlandi, Fabio; Limone, Paolo Piero; Arvat, Emanuela; Boccuzzi, Giuseppe; Piovesan, Alessandro

    2016-01-01

    Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11. PMID:27766105

  16. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study.

    PubMed

    Mateos, María-Victoria; Hernández, José-M; Hernández, Miguel-T; Gutiérrez, Norma-C; Palomera, Luis; Fuertes, Marta; Díaz-Mediavilla, Joaquín; Lahuerta, Juan-J; de la Rubia, Javier; Terol, María-José; Sureda, Ana; Bargay, Joan; Ribas, Paz; de Arriba, Felipe; Alegre, Adrian; Oriol, Albert; Carrera, Dolores; García-Laraña, José; García-Sanz, Ramón; Bladé, Joan; Prósper, Felipe; Mateo, Gemma; Esseltine, Dixie-Lee; van de Velde, Helgi; San Miguel, Jesús-F

    2006-10-01

    Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.

  17. A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA–IIIB esophageal squamous cell carcinoma

    PubMed Central

    Zheng, Yan; Liu, Xianben; Zhang, Ruixiang; Wang, Zongfei; Sun, Haibo; Liu, Shilei

    2017-01-01

    Background The survival benefits of neoadjuvant chemotherapy (NAC) for esophagus squamous cell carcinoma (ESCC) remains controversial. The surgical procedure was not well defined in NAC strategy, in past trials. The different surgical procedure and different levels of lymphadenectomy may decrease the survival benefits from NAC. The new chemotherapy regimen with paclitaxel is promising. The purpose of this study is to confirm the superiority of paclitaxel, cisplatin and McKeown esophagectomy with total two-field lymphadenectomy compared with surgery alone for ESCC. Methods A two-arm phase III trial was launched in June 2015. A total of 528 patients will be recruited from eight Chinese institutions within 2.5 years. The overall survival (OS) is the primary endpoint, and the secondary endpoints include disease-free survival (DFS), R0 resection rate, complication rate, perioperation mortality, days of hospitalization, quality of life (QOL), NAC response rate, pathologic response rate, toxicities of NAC, prognostic factors, predictive factors, progression-free survival (PFS), and adverse events. Discussion The study will provide the final conclusion of NAC for ESCC in China. Trial registration NCT02442440 (https://register.clinicaltrials.gov/). PMID:28203424

  18. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia.

    PubMed

    Zeidner, Joshua F; Foster, Matthew C; Blackford, Amanda L; Litzow, Mark R; Morris, Lawrence E; Strickland, Stephen A; Lancet, Jeffrey E; Bose, Prithviraj; Levy, M Yair; Tibes, Raoul; Gojo, Ivana; Gocke, Christopher D; Rosner, Gary L; Little, Richard F; Wright, John J; Doyle, L Austin; Smith, B Douglas; Karp, Judith E

    2015-09-01

    Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m(2) days 1-3, cytarabine 667 mg/m(2)/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m(2) day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011-July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m(2)/day continuous infusion days 1-7 and daunorubicin 90 mg/m(2) days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m(2)/day continuous infusion days 1-5 and daunorubicin 45 mg/m(2) days 1-2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development. This study is registered with clinicaltrials.gov identifier: 01349972.

  19. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

    PubMed Central

    Zeidner, Joshua F.; Foster, Matthew C.; Blackford, Amanda L.; Litzow, Mark R.; Morris, Lawrence E.; Strickland, Stephen A.; Lancet, Jeffrey E.; Bose, Prithviraj; Levy, M. Yair; Tibes, Raoul; Gojo, Ivana; Gocke, Christopher D.; Rosner, Gary L.; Little, Richard F.; Wright, John J.; Doyle, L. Austin; Smith, B. Douglas; Karp, Judith E.

    2015-01-01

    Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m2 days 1–3, cytarabine 667 mg/m2/day continuous infusion days 6–8, and mitoxantrone (FLAM) 40 mg/m2 day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011–July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18–70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m2/day continuous infusion days 1–7 and daunorubicin 90 mg/m2 days 1–3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m2/day continuous infusion days 1–5 and daunorubicin 45 mg/m2 days 1–2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/−5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development. This study is registered with clinicaltrials.gov identifier: 01349972. PMID:26022709

  20. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea

    PubMed Central

    Lee, Hee Seung; Chung, Moon Jae; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Kim, Ho Gak; Noh, Myung Hwan; Lee, Sang Hyub; Kim, Yong-Tae; Kim, Hyo Jung; Kim, Chang Duck; Lee, Dong Ki; Cho, Kwang Bum; Cho, Chang Min; Moon, Jong Ho; Kim, Dong Uk; Kang, Dae Hwan; Cheon, Young Koog; Choi, Ho Soon; Kim, Tae Hyeon; Kim, Jae Kwang; Moon, Jieun; Shin, Hye Jung; Song, Si Young

    2017-01-01

    Abstract Background: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy. Methods: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m2 plus Gem 1000 mg/m2 by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks). Results: Median overall survival (OS) time, the primary end point, was 10.3 and 7.5 months in the GemCap and Gem arms, respectively (P = 0.06). Progression-free survival was 6.2 and 5.3 months in the GemCap and Gem arms, respectively (P = 0.08). GemCap significantly improved overall response rate compared with Gem alone (43.7% vs 17.6%; P = 0.001). Overall frequency of grade 3 or 4 toxicities was similar in each group. Neutropenia was the most frequent grade 3 or 4 toxicity in both groups. Conclusion: GemCap failed to improve OS at a statistically significant level compared to Gem treatment. This study showed a trend toward improved OS compared to Gem alone. GemCap and Gem both exhibited similar safety profiles. PMID:28072706

  1. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

    PubMed Central

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

    2016-01-01

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

  2. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

    PubMed

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I; Fischer, Kathelijn; Gill, Joan C; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St Ledger, Katie; Pabinger, Ingrid

    2016-08-04

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

  3. Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

    SciTech Connect

    Strnad, Vratislav; Hildebrandt, Guido; Poetter, Richard; Hammer, Josef; Hindemith, Marion; Resch, Alexandra; Spiegl, Kurt; Lotter, Michael; Uter, Wolfgang; Bani, Mayada; Kortmann, Rolf-Dieter; Beckmann, Matthias W.; Fietkau, Rainer; Ott, Oliver J.

    2011-05-01

    Purpose: To evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer. Methods and Materials: 274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D{sub ref} = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D{sub ref} = 32.0 Gy). Results: Median follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects {>=}Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%). Conclusions: The long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

  4. A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients

    PubMed Central

    Lee, Eudocia Q.; Kaley, Thomas J.; Duda, Dan G.; Schiff, David; Lassman, Andrew B.; Wong, Eric T.; Mikkelsen, Tom; Purow, Benjamin W.; Muzikansky, Alona; Ancukiewicz, Marek; Huse, Jason T.; Ramkissoon, Shakti; Drappatz, Jan; Norden, Andrew D.; Beroukhim, Rameen; Weiss, Stephanie E.; Alexander, Brian M.; McCluskey, Christine S.; Gerard, Mary; Smith, Katrina H.; Jain, Rakesh K.; Batchelor, Tracy T.; Ligon, Keith L.; Wen, Patrick Y.

    2016-01-01

    Purpose Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM). Experimental Design We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18 years, Karnofsky performance status (KPS) ≥ 60, and not on enzyme-inducing antiepileptics were eligible. Primary end-point was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis. Results The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0–22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9–20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75). Conclusions The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study. PMID:25910950

  5. A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib

    PubMed Central

    Ganjoo, K. N.; Villalobos, V. M.; Kamaya, A.; Fisher, G. A.; Butrynski, J. E.; Morgan, J. A.; Wagner, A. J.; D'Adamo, D.; McMillan, A.; Demetri, G. D.; George, S.

    2014-01-01

    Background Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (−1, −2, and −3), and PDGFR (-α and-β) in patients with advanced GIST following failure of at least imatinib and sunitinib. Methods Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. Results Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2–7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5–37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6–5.2), and the median OS was 10.7 months (95% CI 3.9–NR). Conclusions Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in

  6. A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer

    PubMed Central

    Friess, Helmut; Langrehr, Jan M; Oettle, Helmut; Raedle, Jochen; Niedergethmann, Marco; Dittrich, Christian; Hossfeld, Dieter K; Stöger, Herbert; Neyns, Bart; Herzog, Peter; Piedbois, Pascal; Dobrowolski, Frank; Scheithauer, Werner; Hawkins, Robert; Katz, Frieder; Balcke, Peter; Vermorken, Jan; van Belle, Simon; Davidson, Neville; Esteve, Albert Abad; Castellano, Daniel; Kleeff, Jörg; Tempia-Caliera, Adrien A; Kovar, Andreas; Nippgen, Johannes

    2006-01-01

    Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. Methods A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Results Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. Conclusion There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The

  7. A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation.

    PubMed

    Hari, Parameswaran; Aljitawi, Omar S; Arce-Lara, Carlos; Nath, Rajneesh; Callander, Natalie; Bhat, Gajanan; Allen, Lee F; Stockerl-Goldstein, Keith

    2015-12-01

    Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National

  8. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.

    PubMed

    Lucasti, Christopher; Hershberger, Ellie; Miller, Benjamin; Yankelev, Sara; Steenbergen, Judith; Friedland, Ian; Solomkin, Joseph

    2014-09-01

    Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, -12.4%; 95% CI, -34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, -7.1%; 95% CI, -30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success against Escherichia coli (89.5%), Klebsiella pneumoniae (100%), and P. aeruginosa (100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in

  9. A prospective, non comparative, multicenter study to investigate the effect of cadexomer iodine on bioburden load and other wound characteristics in diabetic foot ulcers.

    PubMed

    Schwartz, Jamie A; Lantis, John C; Gendics, Cynthia; Fuller, Amy M; Payne, Wyatt; Ochs, Diane

    2013-04-01

    Few studies regarding wound treatment with topical antimicrobials evaluate change in the bacterial bioburden of the wound with treatment. This study sought out to determine the in vivo effect of cadexomer iodine antibacterial dressing on diabetic foot ulcers (DFUs) that were infected or achieved a critical level of colonisation, looking specifically at wound progression in relation to bioburden. Fifteen patients corresponding to 16 total DFUs met criteria of displaying clinical signs of infection or critical colonisation and were suitable for a topical antibacterial dressing. They underwent weekly treatment for 6 weeks. Cultures were taken at week 0, 3 and 6 as appropriate. At week 6 median log10 bacterial count reduction of 1.0 was observed from baseline (p = 0·025). At week 3- a median log10 bacterial count reduction of 0.3 was observed from baseline (p = 0·049). Over the study period there was a 53.6% median reduction of the wound surface area. There were no patients that completely healed their ulcer over the 6 week study period. There was a statistically significant median reduction in the bacterial load over the 6 week period (p = 0·025) as well as 3 weeks (p = 0·049). This was accompanied by a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final.

  10. Piperacillin/tazobactam in the treatment of lower respiratory tract infections: an open non-comparative and multicentered trial. Latin American Clinical Research Group.

    PubMed

    Sifuentes-Osornio, J; Ruíz-Palacios, G M; Jakob, E; Rojas, J J; Jáuregui, A; Villalobos, Y

    1994-06-01

    The aim of this study was to determine the clinical and bacteriological efficacy and safety of piperacillin-tazobactam (PT) (4g/500 mg IV tid) in the treatment of 107 adult patients with lower respiratory tract infections (LRTI) requiring hospitalization. Patients included were 66 men and 41 women with a mean age of 55.2 years (range 18-89), enrolled from Mexican (6) and Argentinean (5) hospitals. Ninety-nine clinically evaluable patients (92.5%), 87 with pneumonia and 12 with bronchitis, were treated for a mean period of 9.3 and 7.3 days, respectively. Response to treatment was favorable in 94.3% cases with pneumonia and 100% of cases with bronchitis; 86 cases (80.3%) were bacteriologically evaluable, 77 with pneumonia (eradication 74, persistence 1, superinfection 2), and 9 with bronchitis (eradication in all). Streptococcus pneumoniae was recovered in 24, Klebsiella pneumoniae in 21, Staphylococcus aureus in 8, Haemophilus influenzae in 7, Pseudomonas aeruginosa in 5, Enterobacter spp. in 6, Escherichia coli in 6 and other organisms in 12. Toxicity or intolerance were not observed. Our data suggest that PT is a reliable therapy for severe LRTI.

  11. SALTO: a randomized, multicenter study assessing octreotide LAR in inoperable bowel obstruction.

    PubMed

    Laval, Guillemette; Rousselot, Hubert; Toussaint-Martel, Sophie; Mayer, Françoise; Terrebonne, Eric; François, Eric; Brixi, Hédia; Nguyen, Thierry; Bourdeix, Isabelle; Bisot-Locard, Ségolène; Zelek, Laurent

    2012-02-01

    This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was "success" at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

  12. Euclidean supergravity and multi-centered solutions

    NASA Astrophysics Data System (ADS)

    Sabra, W. A.

    2017-04-01

    In ungauged supergravity theories, the no-force condition for BPS states implies the existence of stable static multi-centered solutions. The first solutions to Einstein-Maxwell theory with a positive cosmological constant describing an arbitrary number of charged black holes were found by Kastor and Traschen. Generalisations to five and higher dimensional theories were obtained by London. Multi-centered solutions in gauged supergravity, even with time-dependence allowed, have yet to be constructed. In this letter we construct supersymmetry-preserving multi-centered solutions for the case of D = 5, N = 2 Euclidean gauged supergravity coupled to an arbitrary number of vector multiplets. Higher dimensional Einstein-Maxwell multi-centered solutions are also presented.

  13. Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

    PubMed

    Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-03-11

    A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris.

  14. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  15. Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001)

    PubMed Central

    Nam, Byung Ho; Reim, Daniel; Eom, Bang Wool; Yu, Wan Sik; Park, Young Kyu; Ryu, Keun Won; Lee, Young Joon; Yoon, Hong Man; Lee, Jun Ho; Jeong, Oh; Jeong, Sang Ho; Lee, Sang Eok; Lee, Sang Ho; Yoon, Ki Young; Seo, Kyung Won; Chung, Ho Young; Kwon, Oh Kyoung; Kim, Tae Bong; Lee, Woon Ki; Park, Seong Heum; Sul, Ji-Young; Yang, Dae Hyun; Lee, Jong Seok

    2013-01-01

    Purpose Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. Materials and Methods Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. Discussion Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea). PMID:24156036

  16. Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

    PubMed Central

    Collaku, Agron; Yue, Yong; Reed, Kenneth

    2017-01-01

    Background/objective Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0=not present to 10=unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. Results A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Conclusion Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed. PMID:28356767

  17. Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

    PubMed

    Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-02-02

    An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris.

  18. Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.

    PubMed

    Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W

    2000-10-01

    Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant

  19. Multicenter Guidelines | Division of Cancer Prevention

    Cancer.gov

    A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

  20. Infliximab-induced autoantibodies: a multicenter study.

    PubMed

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  1. Quality Assurance of 4D-CT Scan Techniques in Multicenter Phase III Trial of Surgery Versus Stereotactic Radiotherapy (Radiosurgery or Surgery for Operable Early Stage (Stage 1A) Non-Small-Cell Lung Cancer [ROSEL] Study)

    SciTech Connect

    Hurkmans, Coen W.; Lieshout, Maarten van; Schuring, Danny; Heumen, Marielle J.T. van; Cuijpers, Johan P.; Lagerwaard, Frank J.; Widder, Joachim; Heide, Uulke A. van der; Senan, Suresh

    2011-07-01

    Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer. Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (Quasar, Modus Medical Devices) in accordance with their in-house imaging protocol for SBRT. A cylindrical cedar wood insert with plastic spheres of 15 mm (o15) and 30 mm (o30) diameter was moved in a cosine-based pattern, with an extended period in the exhale position to mimic the actual breathing motion. A range of motion of R = 15 and R = 25 mm and breathing period of T = 3 and T = 6 s were used. Positional and volumetric imaging accuracy was analyzed using Pinnacle version 8.1x at various breathing phases, including the mid-ventilation phase and maximal intensity projections of the spheres. Results: Imaging using eight CT scanners (Philips, Siemens, GE) and one positron emission tomography-CT scanner (Institution 3, Siemens) was investigated. The imaging protocols varied widely among the institutions. No strong correlation was found between the specific scan protocol parameters and the observed results. Deviations in the maximal intensity projection volumes averaged 1.9% (starting phase of the breathing cycle [o]15, R = 15), 12.3% (o15, R = 25), and -0.9% (o30, R = 15). The end-expiration volume deviations (13.4%, o15 and 2.5%, o30), were, on average, smaller than the end-inspiration deviations (20.7%, o15 and 4.5%, o30), which, in turn, were smaller than the mid-ventilation deviations (32.6%, o15 and 8.0%, o30). A slightly larger variation in the mid-ventilation origin position was observed (mean, -0.2 mm; range, -3.6-4.2) than in the maximal intensity projection origin position (mean, -0.1 mm; range, -2.5-2.5). The range of motion was generally underestimated (mean, -1.5 mm; range, -5.5-1). Conclusions: Notable differences were seen in the 4D-CT imaging protocols

  2. Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized, parallel-group, multicenter, extension clinical trial

    PubMed Central

    Fujishiro, Mitsuhiro; Higuchi, Kazuhide; Kato, Mototsugu; Kinoshita, Yoshikazu; Iwakiri, Ryuichi; Watanabe, Toshio; Takeuchi, Toshihisa; Sugisaki, Nobuyuki; Okada, Yasushi; Ogawa, Hisao; Arakawa, Tetsuo; Fujimoto, Kazuma

    2015-01-01

    A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated. PMID:26060354

  3. Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized, parallel-group, multicenter, extension clinical trial.

    PubMed

    Fujishiro, Mitsuhiro; Higuchi, Kazuhide; Kato, Mototsugu; Kinoshita, Yoshikazu; Iwakiri, Ryuichi; Watanabe, Toshio; Takeuchi, Toshihisa; Sugisaki, Nobuyuki; Okada, Yasushi; Ogawa, Hisao; Arakawa, Tetsuo; Fujimoto, Kazuma

    2015-05-01

    A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.

  4. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial

    PubMed Central

    Al-Ali, Haifa Kathrin; Griesshammer, Martin; le Coutre, Philipp; Waller, Cornelius F.; Liberati, Anna Marina; Schafhausen, Philippe; Tavares, Renato; Giraldo, Pilar; Foltz, Lynda; Raanani, Pia; Gupta, Vikas; Tannir, Bayane; Ronco, Julian Perez; Ghosh, Jagannath; Martino, Bruno; Vannucchi, Alessandro M.

    2016-01-01

    JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis – a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib’s mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov. PMID:27247324

  5. A phase I multicenter study of antroquinonol in patients with metastatic non-small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen

    PubMed Central

    LEE, YU-CHIN; HO, CHING-LIANG; KAO, WOEI-YAU; CHEN, YUH-MIN

    2015-01-01

    Antroquinonol is isolated from Antrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. This first-in-human phase I study of antroquinonol included patients with metastatic non-small-cell lung cancer who had received at least two prior systemic treatment regimens. An open-label, dose escalation, pharmacokinetic (PK) study was conducted to determine the maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), and safety/tolerability and preliminary efficacy profiles of antroquinonol. The patients received escalating doses of once-daily antroquinonol in 4-week cycles (up to 3 cycles). The escalated doses were 50–600 mg. PKs were evaluated on day 1 and 28 of cycle 1. Between January, 2011 and October, 2012, 13 patients with metastatic adenocarcinoma were enrolled. No DLTs occurred in any patient at any dose level. Tmax was observed between 1.00 and 3.70 h under single-dose conditions, and at 1.92–4.05 h under multiple-dose conditions. The mean elimination half-life ranged between 1.30 and 4.33 h, independent of the treatment dose. Antroquinonol at all dose levels had a mild toxicity profile, with no reported treatment-related mortality. The most common treatment-related adverse events were diarrhea, vomiting and nausea. The best tumor response was stable disease in 3 patients. In conclusion, antroquinonol at all dose levels, administered daily for 4 weeks, was generally safe and well tolerated, without DLTs. The recommended dose level for a phase II study is ≥600 mg daily. PMID:26807250

  6. MR-guided focused ultrasound (MRgFUS) is effective for the distinct pattern of uterine fibroids seen in African-American women: data from phase III/IV, non-randomized, multicenter clinical trials

    PubMed Central

    2013-01-01

    Background Uterine fibroids are common among women at the reproductive age. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel and a conservative treatment for symptomatic cases. The aim of the study was to evaluate the efficacy of MRgFUS in African-American (AA) women compared with that in non-African-Americans (non-AA). Methods A single-armed phase IV study was conducted to establish the efficacy of treatment in AA women. Comparison of patient, fibroid, and treatment characteristics from this trial was compared with that of the previously published phase III trial. Both studies were approved by the IRB of each medical center. Results Sixty-three AA and 59 non-AA women were treated with MRgFUS. Although AA women had a different pattern of disease, outcomes were similar in both groups. AA patients had a significant higher total number of fibroids compared with non-AA (median 6.0, interquartile range (IQR) 3.0–10.0 vs. 2.0, IQR 1.0–4.0, respectively, p < 0.001), although their total fibroid volume was significantly smaller (median 196.9 cm3, IQR 112.8–415.3 cm3 vs. 394.8 cm3, IQR 189.8–674.4 cm3, respectively, p < 0.001). AA women were younger compared with non-AA (mean ± SD 43.4 ± 5.1 vs. 46.3 ± 4.1 years of age, respectively, p = 0.001) when they presented for treatment. The rate of alternative treatments as well as fibroid-associated symptoms at follow-up time points (3, 6, 12, 24, and 36 months, period following MRgFUS treatment) did not differ according to race (p ≥ 0.62). Conclusion Despite differences in the pattern of fibroid disease, MRgFUS for uterine fibroids has a similar efficacy for AA women compared with non-AA women. PMID:25232480

  7. Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O(6)-Methylguanine-DNA Methyltransferase Biomarker Analyses.

    PubMed

    Cloughesy, Timothy; Finocchiaro, Gaetano; Belda-Iniesta, Cristóbal; Recht, Lawrence; Brandes, Alba A; Pineda, Estela; Mikkelsen, Tom; Chinot, Olivier L; Balana, Carmen; Macdonald, David R; Westphal, Manfred; Hopkins, Kirsten; Weller, Michael; Bais, Carlos; Sandmann, Thomas; Bruey, Jean-Marie; Koeppen, Hartmut; Liu, Bo; Verret, Wendy; Phan, See-Chun; Shames, David S

    2017-01-20

    Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O(6)-methylguanine-DNA methyltransferase promoter methylation, and glioblastoma subtype. Results Among 129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline characteristics were balanced. The median progression-free survival was 3.9 months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% CI, 0.72 to 1.56; P = .7444). The median overall survival was 8.8 months for Ona + Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37; P = .1389). Grade ≥ 3 adverse events were reported in 38.5% of patients who received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory biomarker analyses suggested that patients with high expression of hepatocyte growth factor or unmethylated O(6)-methylguanine-DNA methyltransferase may benefit from Ona + Bev. Conclusion There was no evidence of further clinical benefit with the addition of onartuzumab to bevacizumab compared with bevacizumab plus placebo in unselected patients with

  8. Safety and Efficacy of Autologous CD34+ Hematopoietic Progenitor Cells Transduced with an Anti-Tat Ribozyme in a Multi-Center, Randomized, Placebo-Controlled, Phase II Gene Therapy Trial for the Human Immunodeficiency Virus

    PubMed Central

    Mitsuyasu, Ronald T; Merigan, Thomas C; Carr, Andrew; Zack, Jerome A; Winters, Mark A; Workman, Cassy; Bloch, Mark; Lalezari, Jacob; Becker, Stephen; Thornton, Lorna; Akil, Bisher; Khanlou, Homayoon; Finlayson, Robert; McFarlane, Robert; Smith, Don E; Garsia, Roger; Ma, David; Law, Matthew; Murray, John M.; von Kalle, Christof; Ely, Julie A; Patino, Sharon M; Knop, Alison E; Wong, Philip; Todd, Alison V; Haughton, Margaret; Fuery, Caroline; Macpherson, Janet L; Symonds, Geoff P; Evans, Louise A; Pond, Susan M; Cooper, David A

    2009-01-01

    SUMMARY Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system, and avoids lifetime highly active antiretroviral therapy. This study, the first randomized, double-blind, placebo-controlled, phase II cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1 infected adults who received a tat/vpr specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistical difference in viral load between the OZ1 and placebo group at the primary end-point (average at weeks 47 and 48) but time weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study provides the first indication that cell-delivered gene transfer is safe and biologically active in HIV patients and can be developed as a conventional therapeutic product. PMID:19219022

  9. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

    PubMed Central

    Greenberg, Richard N; Hurley, Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; Chaplin, Paul

    2015-01-01

    Background Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. Results The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602 PMID:26439129

  10. Multicenter phase II study of infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, plus biweekly cetuximab as first-line treatment in patients with metastatic colorectal cancer (CELINE trial)

    PubMed Central

    Kotake, Masanori; Aoyama, Toru; Munemoto, Yoshinori; Doden, Kenji; Kataoka, Masato; Kobayashi, Kenji; Nishimura, Genichi; Fujita, Hidehito; Nakamura, Keishi; Takehara, Akira; Tanaka, Chihiro; Sakamoto, Junichi; Nagata, Naoki; Oba, Koji; Kondo, Ken

    2017-01-01

    The current phase II study investigated the efficacy and safety of biweekly cetuximab combined with standard oxaliplatin-based chemotherapy [infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX-6)] in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC). Sixty patients with a median age of 64 years (range, 38–82 syears) received a biweekly intravenous infusion of cetuximab (500 mg/m2 on day 1) followed by FOLFOX-6 (2-hour oxaliplatin 85 mg/m2 infusion on day 1 in tandem with a 2-h leucovorin 200 mg/m2 infusion on days 1 and 2, and 5-FU as a 400 mg/m2 bolus followed by a 46-hour 2,400 mg/m2 infusion on days 1–3). Patient response rate was 70%, with 95% disease control rates. The median progression-free survival was 13.8 months. Thirteen patients (21.7%) were able to undergo resection of previously unresectable metastases, with the aim of curing them. The median follow-up was 22.7 months, and median overall survival was 31.0 months. Cetuximab did not increase FOLFOX-6 toxicity and was generally well tolerated. The results of the current study demonstrate that the combination of biweekly cetuximab with FOLFOX-6 was well tolerated and had a manageable safety profile for the first-line treatment of KRAS wild-type metastatic colorectal cancer. Efficacy was comparable to other treatment regimens. The results support the administration of biweekly cetuximab in combination with FOLFOX-6, which may be more convenient and provide treatment flexibility in this setting for patients with metastatic colorectal cancers.

  11. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

    SciTech Connect

    Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.; Zalupski, Mark M.; Kim, Edward J.; Bekaii-Saab, Tanios S.; Ben-Josef, Edgar; Dawson, Laura A.; Ringash, Jolie; Wei, Alice C.

    2014-10-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  12. A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis.

    PubMed

    Viljoen, J; Azie, N; Schmitt-Hoffmann, A-H; Ghannoum, M

    2015-03-01

    Esophageal candidiasis is a frequent cause of morbidity in immunocompromised patients. Isavuconazole is a novel, broad-spectrum antifungal developed for the treatment of opportunistic fungal infections. This phase 2 trial compared the efficacy and safety of three oral dosing regimens of isavuconazole with an oral fluconazole regimen in the primary treatment of uncomplicated esophageal candidiasis. The isavuconazole regimens were as follows: 200 mg on day 1 and then 50 mg once daily (arm A), 400 mg on day 1 and then 400 mg once-weekly (arm B), and 400 mg on day 1 and then 100 mg once daily (arm C). Patients in arm D received fluconazole at 200 mg on day 1 and then 100 mg once daily. The minimum treatment duration was 14 days. The primary endpoint was the rate of endoscopically confirmed clinical response at end of therapy. Safety and tolerability were also assessed. Efficacy was evaluated in 153 of 160 enrolled patients. Overall, 146 (95.4%) achieved endoscopically confirmed clinical success. Each of the isavuconazole regimens was shown to be not inferior to fluconazole, i.e., arm A versus D, -0.5% (95% confidence interval [CI] -10.0 to 9.4), arm B versus D, 3.5% (95% CI, -5.6 to 12.7), and arm C versus D, -0.2% (95% CI, -9.8 to 9.4). The frequency of adverse events was similar in arm A (n = 22; 55%), arm B (n = 18; 45%), and arm D (n = 22; 58%), but higher in arm C (n = 29; 71%). In summary, efficacy and safety of once-daily and once-weekly isavuconazole were comparable with once-daily fluconazole in the primary treatment of uncomplicated esophageal candidiasis.

  13. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

    PubMed Central

    Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

    2015-01-01

    Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

  14. A Bayesian Approach to Multicenter Trials and Metaanalysis.

    ERIC Educational Resources Information Center

    Berry, Donald A.

    The use of a Bayesian approach in evaluating data from clinical trials with many treatment centers and from many studies is discussed. The main distinction between a metaanalysis and an analysis of a multicenter trial is that different studies may have very different designs, while the centers in a multicenter trial usually follow the same…

  15. Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

    PubMed Central

    Puhalla, Shannon; Wilks, Sharon; Brufsky, Adam M; O’Shaughnessy, Joyce; Schwartzberg, Lee S; Berrak, Erhan; Song, James; Vahdat, Linda

    2016-01-01

    Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg) on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant) trastuzumab treatment. Fifty-two patients (median age: 59.5 years) received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21) had been previously treated with neo/adjuvant trastuzumab prior to treatment with eribulin plus trastuzumab for metastatic disease (median time between neo/adjuvant and study treatment: 23 months). In trastuzumab-naïve patients (n=31) compared with those who had received prior trastuzumab, objective response rate was 77.4% versus 61.9%, respectively; duration of response was 11.8 versus 9.5 months, respectively; clinical benefit rate was 87.1% versus 81.0%, respectively; and median progression-free survival was 12.2 versus 11.5 months, respectively. The most common grade 3/4 treatment-emergent adverse events (occuring in ≥5% of patients) in patients who received prior trastuzumab versus trastuzumab naïve patients, respectively, were neutropenia (47.6% vs 32.3%), peripheral neuropathy (14

  16. OnWARD: ontology-driven web-based framework for multi-center clinical studies.

    PubMed

    Tran, Van-Anh; Johnson, Nathan; Redline, Susan; Zhang, Guo-Qiang

    2011-12-01

    With a large percentage of clinical trials still using paper forms as the primary data collection tool, there is much potential for increasing efficiency through web-based data collection systems, especially for large-scale multi-center trials. This paper presents OnWARD, an ontology-driven, secure, rapidly-deployed, web-based framework supporting data capture for large-scale multi-center clinical research. Our approach is developed using the agile methodology to provide a flexible, user-centered dynamic form generator, which can be quickly deployed and customized for any clinical study without the need of deep technical expertise. Because of the flexible framework, the data management system can be extended to accommodate a large variety of data types, including genetic, genomic and proteomic data. In this paper, we demonstrate the initial deployment of OnWARD for a Phase II multi-center clinical trial after a development period of merely three months. The study utilizes 23 clinical report forms containing more than 1500 data points. Preliminary evaluation results show that OnWARD exceeded expectations of the clinical investigators in efficiency, flexibility and ease in setting up.

  17. Multicenter Epidemiological Studies of Atherosclerosis Imaging

    PubMed Central

    Liu, Songtao; Bluemke, David A.

    2011-01-01

    Cardiovascular disease is the leading course of death and disability. Conventional cardiac risk factors do not fully explain the level of cardiovascular risk, incidence of coronary artery disease, and coronary events. Risk stratification and therapy based solely on these conventional risk factors may overlook a population who would benefit from lifestyle and risk factor modification. Thus, research has recently focused on improving risk assessment with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging, both in coronary and extracoronary arterial beds, has proven to be very helpful in this regard. In this article, we review the current literature from multicenter epidemiology studies on the utility of noninvasive imaging modalities for risk stratification in the context of conventional risk factor evaluation. PMID:20805734

  18. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-10-1-0894 TITLE: Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration PRINCIPAL...DATES COVERED 15Sep2010 - 14Sep2015 4. TITLE AND SUBTITLE Multicenter Clinical Trial of Keratin Biomaterial for 5a. CONTRACT NUMBER W81XWH-10-1-0894... clinical trial was to be initiated as soon as the FDA provided an IND for the keratin biomaterial hydrogel. However, due to delays in the FDA approval

  19. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2014-10-01

    AD_________________ Award Number: W81XWH-10-1-0894 TITLE: Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration...DATES COVERED 15 Sep 2013 - 14 Sep 2014 4. TITLE AND SUBTITLE Multicenter Clinical Trial of Keratin Biomaterial for 5a. CONTRACT NUMBER Peripheral...has developed a keratin biomaterial hydrogel that can be used as luminal filler in nerve guidance conduits to facilitate nerve regeneration

  20. Acute necrotizing pancreatitis: a multicenter study.

    PubMed

    Fernández-Cruz, L; Navarro, S; Valderrama, R; Sáenz, A; Guarner, L; Aparisi, L; Espi, A; Jaurietta, E; Marruecos, L; Gener, J

    1994-04-01

    A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

  1. Wandering spleen in children: multicenter retrospective study.

    PubMed

    Fiquet-Francois, Caroline; Belouadah, Mohamed; Ludot, Hugues; Defauw, Benoit; Mcheik, Jiad Noel; Bonnet, Jean Paul; Kanmegne, Charly Udozen; Weil, Dominique; Coupry, Lionel; Fremont, Benjamin; Becmeur, Francois; Lacreuse, Isabelle; Montupet, Philippe; Rahal, Eliane; Botto, Nathalie; Cheikhelard, Alaa; Sarnacki, Sabine; Petit, Thierry; Poli Merol, Marie Laurence

    2010-07-01

    Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

  2. A Guide on Organizing a Multicenter Clinical Trial: the WRIST study group

    PubMed Central

    Chung, Kevin C.; Song, Jae W.

    2010-01-01

    Multicenter clinical trials (MCCTs) are an important research tool. Planning a MCCT is a long and arduous task that requires substantial preparation time. In this guide, we discuss the steps to plan a MCCT. A pre-planning phase, which involves formulating and refining a research question and conducting pilot studies, is detailed as well as the planning phase, which involves the acquisition of funding to support the coordination and preparation of a MCCT, culminating in the submission of an R01 grant. An essential asset to planning a MCCT is the fluidity with which all collaborators work together towards a common vision. The philosophy among collaborators should be consensus and commitment and is emphasized by the development of a consensus-assisted study protocol and the recruitment of centers and co-investigators who are dedicated, collaborative and selfless in this team effort to achieve goals that cannot be reached by a single center effort. PMID:20375760

  3. Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

    ClinicalTrials.gov

    2017-03-28

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  4. Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus

    PubMed Central

    Arendrup, M.C.; Warris, A.; Lagrou, K.; Pelloux, H.; Hauser, P.M.; Chryssanthou, E.; Mellado, E.; Kidd, S.E.; Tortorano, A.M.; Dannaoui, E.; Gaustad, P.; Baddley, J.W.; Uekötter, A.; Lass-Flörl, C.; Klimko, N.; Moore, C.B.; Denning, D.W.; Pasqualotto, A.C.; Kibbler, C.; Arikan-Akdagli, S.; Andes, D.; Meletiadis, J.; Naumiuk, L.; Nucci, M.; Melchers, W.J.G.; Verweij, P.E.

    2015-01-01

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. PMID:25988348

  5. Multicenter patient records research: security policies and tools.

    PubMed

    Behlen, F M; Johnson, S B

    1999-01-01

    The expanding health information infrastructure offers the promise of new medical knowledge drawn from patient records. Such promise will never be fulfilled, however, unless researchers first address policy issues regarding the rights and interests of both the patients and the institutions who hold their records. In this article, the authors analyze the interests of patients and institutions in light of public policy and institutional needs. They conclude that the multicenter study, with Institutional Review Board approval of each study at each site, protects the interests of both. "Anonymity" is no panacea, since patient records are so rich in information that they can never be truly anonymous. Researchers must earn and respect the trust of the public, as responsible stewards of facts about patients' lives. The authors find that computer security tools are needed to administer multicenter patient records studies and describe simple approaches that can be implemented using commercial database products.

  6. Multi-Center Traffic Management Advisor Operational Field Test Results

    NASA Technical Reports Server (NTRS)

    Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

    2005-01-01

    The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

  7. The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease

    PubMed Central

    Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.

    2017-01-01

    Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. PMID:26196261

  8. Multicenter evaluation of crystal violet decolorization assay (CVDA) for rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis

    PubMed Central

    Coban, Ahmet Yilmaz; Akbal, Ahmet Ugur; Bicmen, Can; Albay, Ali; Sig, Ali Korhan; Uzun, Meltem; Selale, Deniz Sertel; Ozkutuk, Nuri; Surucuoglu, Suheyla; Albayrak, Nurhan; Ucarman, Nilay; Ozkutuk, Aydan; Esen, Nuran; Ceyhan, Ismail; Ozyurt, Mustafa; Bektore, Bayhan; Aslan, Gonul; Delialioğlu, Nuran; Alp, Alpaslan

    2016-01-01

    The aim of this multicenter study was to evaluate the performance of the crystal violet decolorization assay (CVDA) for detection of multidrug resistant tuberculosis (MDR-TB). This study was performed in 11 centers in two phases. A total of 156 isolates were tested for INH and RIF resistance. In the phase I, 106 clinical isolates were tested in the Center 1–7. In the phase 2, 156 clinical isolates were tested in the center 1–6, center 8–11. Eighty six of 156 tested isolates were the same in phase I. Agreements were 96.2–96.8% for INH and 98.1–98.7% for RIF in the phase I-II, respectively. Mean time to obtain the results in the phase I was 14.3 ± 5.4 days. In the phase II, mean time to obtain the results was 11.6 ± 3.5 days. Test results were obtained within 14days for 62.3% (66/106) of isolates in the phase I and 81.4% (127/156) of isolates in the phase II. In conclusion, CVDA is rapid, reliable, inexpensive, and easy to perform for rapid detection of MDR-TB isolates. In addition, it could be adapted for drug susceptibility testing with all drugs both in developed and developing countries. PMID:27982061

  9. [Multicenter trial for sudden hearing loss therapy - planning and concept].

    PubMed

    Plontke, S K; Girndt, M; Meisner, C; Probst, R; Oerlecke, I; Richter, M; Steighardt, J; Dreier, G; Weber, A; Baumann, I; Plößl, S; Löhler, J; Laszig, R; Werner, J A; Rahne, T

    2016-04-01

    Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

  10. Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

    PubMed Central

    Ugurluer, Gamze; Miller, Robert C.; Li, Yexiong; Thariat, Juliette; Ghadjar, Pirus; Schick, Ulrike; Ozsahin, Mahmut

    2016-01-01

    Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions. Liver function tests were elevated in 56.1% of patients. The most common histopathological diagnosis was diffuse large B-cell lymphoma (65.9%). Most of the patients received Chop-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens; 4 patients received radiotherapy (dose range, 30.6-40.0 Gy). Median survival was 163 months, and 5- and 10-year overall survival rates were 77 and 59%, respectively. The 5- and 10-year disease-free and lymphoma-specific survival rates were 69, 56, 87 and 70%, respectively. Multivariate analysis revealed that fever, weight loss, and normal hemoglobin level were the independent factors influencing the outcome. In this retrospective multicenter RCN study, patients with PHL had a relatively better prognosis than that reported elsewhere. Multicenter prospective studies are still warranted to establish treatment guidelines, outcome, and prognostic factors. PMID:27746888

  11. MAIN ETHICAL BREACHES IN MULTICENTER CLINICAL TRIALS REGULATIONS OF TURKEY

    PubMed Central

    Ekmekci, P. Elif

    2017-01-01

    Turkey has been a growing market for multicenter clinical trials for the last ten years and is considered among the top ten countries in terms of potential study subject populations. The objective of increasing the share of Turkey in multicenter clinical trials is strongly supported. This ambitious goal of Turkey raises the need to have regulations in compliance with other leading countries conducting clinical trials. The latest published Turkish regulations on clinical trials are structured in compliance with the International Conference on Harmonization (ICH) Guidelines and in harmony with the regulations of other leading countries in clinical research, such as the US. There are still flaws in Turkish regulation with the risk of violating human subjects’ rights and issues with responsible conduct of research. The aim of this article is to compare Turkish clinical trials regulations with those of the US, to determine if there exists any incompatibility between the countries’ regulations and, if so, how to ameliorate these. The main flaws in Turkish clinical trials regulations are identified as follows: lack of definition of the term “human subject; absence of explicit referral to the unacceptability of Conflict of Interest (COI) and taking measures to avoid it; exiguity of emphasis on plurality of the IRB members; nonexistence of a clear expression that this is research; and clinical equipoise, regarding the treatment of the existing clinical problem and lack of integration with international accreditation systems for Institutional Review Boards.

  12. Research and operational applications in multi-center ensemble forecasting

    NASA Astrophysics Data System (ADS)

    Zhu, Y.; Toth, Z.

    2009-05-01

    The North American Ensemble Forecast System (NAEFS) was built up in 2004 by the Meteorological Service of Canada (MSC), the National Meteorological Service of Mexico (NMSM), and the US National Weather Service (NWS) as an operational multi-center ensemble forecast system. Currently it combines the 20-member MSC and NWS ensembles to form a joint ensemble of 40 members twice a day. The joint ensemble forecast, after bias correction and statistical downscaling, is used to generate a suite of products for CONUS, North America and for other regions of the globe. The THORPEX Interactive Grand Global Ensemble (TIGGE) project has been established a few years ago to collect operational global ensemble forecasts from world centers, and distribute to the scientific community, to encourage research leading to the acceleration of improvements in the skill and utility of high impact weather forecasts. TIGGE research is expected to advise the development of the operational NAEFS system and eventually the two projects are expected to converge into a single operational system, the Global Interactive Forecast System (GIFS). This presentation will review recent developments, the current status, and plans related to the TIGGE research and NAEFS operational multi-center ensemble projects.

  13. Computational method for general multicenter electronic structure calculations.

    PubMed

    Batcho, P F

    2000-06-01

    Here a three-dimensional fully numerical (i.e., chemical basis-set free) method [P. F. Batcho, Phys. Rev. A 57, 6 (1998)], is formulated and applied to the calculation of the electronic structure of general multicenter Hamiltonian systems. The numerical method is presented and applied to the solution of Schrödinger-type operators, where a given number of nuclei point singularities is present in the potential field. The numerical method combines the rapid "exponential" convergence rates of modern spectral methods with the multiresolution flexibility of finite element methods, and can be viewed as an extension of the spectral element method. The approximation of cusps in the wave function and the formulation of multicenter nuclei singularities are efficiently dealt with by the combination of a coordinate transformation and a piecewise variational spectral approximation. The complete system can be efficiently inverted by established iterative methods for elliptical partial differential equations; an application of the method is presented for atomic, diatomic, and triatomic systems, and comparisons are made to the literature when possible. In particular, local density approximations are studied within the context of Kohn-Sham density functional theory, and are presented for selected subsets of atomic and diatomic molecules as well as the ozone molecule.

  14. Hydrogen multicenter bond in oxide and nitride semiconductors

    NASA Astrophysics Data System (ADS)

    Janotti, Anderson

    2009-03-01

    Hydrogen is a very reactive atom, occurring in virtually all organic and in many inorganic compounds. It can form a purely covalent bond, in which two hydrogen atoms share a pair of electrons in a two-electron two-center bond, as well as polar covalent bonds, such as in an H2O molecule. In solids, hydrogen is usually considered as an interstitial impurity. In elemental semiconductors, such as silicon, hydrogen forms a three-center bond when located at the bond center. In compound semiconductors, hydrogen bonds to the anionic species in p-type material, and to the cationic species in n-type. Thus far, hydrogen in solids has been found to form chemical bonds with one, two, or at most three other atoms. Higher coordination numbers are exceedingly rare and have been reported only for clusters. In this talk we will show that hydrogen is capable of forming multicenter bonds in solids, occupying substitutional sites. As examples, we discuss substitutional hydrogen impurities in oxides (ZnO, MgO, SnO2, TiO2) [1,2] and nitrides (InN, AlN, GaN) [3]. Based on first-principles calculations we show that hydrogen replaces oxygen (nitrogen) and forms genuine chemical bonds with multiple metal atoms, in truly multicoordinated configurations. These multicenter bonds are surprisingly strong despite the large hydrogen-metal distances when compared to typical values in hydrogen two-center bonds. Hydrogen in the multicenter bond configuration is a shallow donor in a number of materials. In conducting oxides, it provides a consistent explanation for the observed dependence of electrical conductivity on oxygen partial pressure, thus resolving a long-standing controversy on the role of point defects in unintentional n-type conductivity [1,2]. [4pt] [1] A. Janotti and C. G Van de Walle, Nature Materials 6, 44 (2007). [0pt] [2] A. K. Singh, A. Janotti, M. Scheffler, and C. G. Van de Walle, Phys. Rev. Lett. 101, 055502 (2008). [0pt] [3] A. Janotti and C. G. Van de Walle, Appl. Phys. Lett. 92

  15. Implementation of the exception from informed consent regulations in a large multicenter emergency clinical trials network: the RAMPART experience.

    PubMed

    Silbergleit, Robert; Biros, Michelle H; Harney, Deneil; Dickert, Neal; Baren, Jill

    2012-04-01

    Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks.

  16. Factors predicting survival in ALS: a multicenter Italian study.

    PubMed

    Calvo, Andrea; Moglia, Cristina; Lunetta, Christian; Marinou, Kalliopi; Ticozzi, Nicola; Ferrante, Gianluca Drago; Scialo, Carlo; Sorarù, Gianni; Trojsi, Francesca; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Chiò, Adriano; Sansone, Valeria Ada; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Monsurrò, Maria Rosaria; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fini, Nicola; Mandrioli, Jessica

    2017-01-01

    The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

  17. The addition of granulocyte-colony stimulating factor shifts the dose limiting toxicity and markedly increases the maximum tolerated dose and activity of the kinesin spindle protein inhibitor SB-743921 in patients with relapsed or refractory lymphoma: results of an international, multicenter phase I/II study.

    PubMed

    O'Connor, Owen A; Gerecitano, John; Van Deventer, Henrik; Hainsworth, John; Zullo, Kelly M; Saikali, Khalil; Seroogy, Joseph; Wolff, Andrew; Escandón, Rafael

    2015-01-01

    This was a phase I study of SB-743921 (SB-921) in patients with relapsed/refractory lymphoma. Previous studies established that neutropenia was the only dose limiting toxicity (DLT). The primary objective was to determine the DLT, maximum tolerated dose (MTD) and efficacy of SB-921 with and without granulocyte-colony stimulating factor (G-CSF). Sixty-eight patients were enrolled, 42 without G-CSF, 26 with G-CSF. In the cohort without G-CSF, SB-921 doses ranged from 2 to 7 mg/m(2), with 6 mg/m(2) being the MTD. In the cohort with G-CSF support, doses of 6-10 mg/m(2) were administered, with 9 mg/m(2) being the MTD, representing a 50% increase in dose density. Fifty-six patients were evaluable for efficacy. Four of 55 patients experienced a partial response (three in Hodgkin lymphoma and one in non-Hodgkin lymphoma, all at doses ≥ 6 mg/m(2)); 19 patients experienced stable disease, 33 patients developed progression of disease. G-CSF shifted the DLT from neutropenia to thrombocytopenia, allowing for a 50% increase in dose density. Responses were seen at higher doses with G-CSF support.

  18. Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

    PubMed Central

    Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

    2015-01-01

    Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

  19. An open multicenter comparative randomized clinical study on chitosan.

    PubMed

    Mo, Xiaohui; Cen, John; Gibson, Elaine; Wang, Robin; Percival, Steven L

    2015-01-01

    Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next-generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management

  20. The Development of the Multi-Center Traffic Management Advisor (MCTMA): Traffic Flow Management Research in a Multi-Facility Environment

    NASA Technical Reports Server (NTRS)

    Lee, Katharine K.; Davis, Thomas J.; Levin, Kerry M.; Rowe, Dennis W.

    2001-01-01

    The Traffic Management Advisor (TMA) is a decision-support tool for traffic managers and air traffic controllers that provides traffic flow visualization and other flow management tools. TMA creates an efficiently sequenced and safely spaced schedule for arrival traffic that meets but does not exceed specified airspace system constraints. TMA is being deployed at selected facilities throughout the National Airspace System in the US as part of the FAA's Free Flight Phase 1 program. TMA development and testing, and its current deployment, focuses on managing the arrival capacity for single major airports within single terminal areas and single en route centers. The next phase of development for this technology is the expansion of the TMA capability to complex facilities in which a terminal area or airport is fed by multiple en route centers, thus creating a multicenter TMA functionality. The focus of the multi-center TMA (McTMA) development is on the busy facilities in the Northeast comdor of the US. This paper describes the planning and development of McTMA and the challenges associated with adapting a successful traffic flow management tool for a very complex airspace.

  1. Low intensity vs. self-guided Internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study

    PubMed Central

    2013-01-01

    Background Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. Methods The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. Discussion The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. Trial registration Clinical Trials NCT01611818 PMID:23312003

  2. A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer.

    PubMed

    Thomas, M; Sadjadian, P; Kollmeier, J; Lowe, J; Mattson, P; Trout, J R; Gargano, M; Patchen, M L; Walsh, R; Beliveau, M; Marier, J F; Bose, N; Gorden, K; Schneller, F

    2017-03-16

    Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m(2) and subsequent doses 250 mg/m(2), weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m(2), Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles; patients who responded or remained stable received maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control arm). Investigator and blinded central radiology reviews were conducted. Efficacy assessments included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, time-to-progression and overall survival (OS); safety was assessed by adverse events (AEs). Potential biomarker analysis for BTH1677 response was also conducted. Results Compared to control treatment, the addition of BTH1677 numerically increased ORR by both investigator (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No other endpoints differed between arms. PK was consistent with previous studies. BTH1677 was well tolerated, with AEs expected of the backbone therapy predominating. Biomarker-positive patients displayed better ORR and OS than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy ClinicalTrials.gov Identifier: NCT

  3. Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study

    PubMed Central

    Cabibbe, Andrea M.; Feuerriegel, Silke; Casali, Nicola; Drobniewski, Francis; Rodionova, Yulia; Bakonyte, Daiva; Stakenas, Petras; Pimkina, Edita; Augustynowicz-Kopeć, Ewa; Degano, Massimo; Ambrosi, Alessandro; Hoffner, Sven; Mansjö, Mikael; Werngren, Jim; Rüsch-Gerdes, Sabine; Niemann, Stefan; Cirillo, Daniela M.

    2014-01-01

    ABSTRACT Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZAr). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZAr strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZAr strains, (iii) mutations with an unclear role found in less than 70% of PZAr strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZAr; the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. PMID:25336456

  4. Emergency Care for Homeless Patients: A French Multicenter Cohort Study

    PubMed Central

    Feral-Pierssens, Anne-Laure; Aubry, Adeline; Truchot, Jennifer; Raynal, Pierre-Alexis; Boiffier, Mathieu; Hutin, Alice; Leleu, Agathe; Debruyne, Geraud; Joly, Luc-Marie; Juvin, Philippe; Riou, Bruno

    2016-01-01

    Objectives. To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. Methods. We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. Results. A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. Conclusions. We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients. PMID:26985613

  5. The Multi-Center Airborne Coherent Atmospheric Wind Sensor, MACAWS

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1997-01-01

    In 1992 the atmospheric lidar remote sensing groups of the NASA Marshall Space Flight Center, NOAA Environmental Technology Laboratory, and Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor, MACAWS, which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in the troposphere and lower stratosphere. A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise which were developed for previous atmospheric research by the respective institutions. The motivation for the MACAWS program Is three-fold: to obtain fundamental measurements of sub-synoptic scale processes and features which may be used as a basis to improve sub-grid scale parameterizations in large-scale models; to obtain similar datasets in order to improve the understanding and predictive capabilities on the mesoscale; and to validate (simulate) the performance of existing (planned) satellite-borne sensors. Examples of the latter include participation in the validation of the NASA Scatterometer and the assessment of prospective satellite Doppler lidar for global tropospheric wind measurement. Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  6. Uterine rupture in pregnancies following myomectomy: A multicenter case series

    PubMed Central

    Kim, Hee-Sun; Oh, Soo-Young; Choi, Suk-Joo; Park, Hyun-Soo; Cho, Geum-Joon; Chung, Jin-Hoon; Seo, Yong-Soo; Jung, Sun-Young; Kim, Jung-Eun; Chae, Su-Hyun

    2016-01-01

    Objective The purpose of this case series was to retrospectively examine records of cases with uterine rupture in pregnancies following myomectomy and to describe the clinical features and pregnancy outcomes. Methods This study was conducted as a multicenter case series. The patient databases at 7 tertiary hospitals were queried. Records of patients with a diagnosis of uterine rupture in the pregnancy following myomectomy between January 2012 and December 2014 were retrospectively collected. The uterine rupture cases enrolled in this study were defined as follows: through-and-through uterine rupture or tear of the uterine muscle and serosa, occurrence from 24+0 to 41+6 weeks’ gestation, singleton pregnancy, and previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status. Results Fourteen pregnant women experienced uterine rupture during their pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks’ gestation occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases had fetal distress. Of the 14 uterine rupture cases, none occurred during labor. All mothers survived and had no sequelae, unlike the perinatal outcomes, although they were receiving blood transfusion or treatment for uterine artery embolization because of uterine atony or massive hemorrhage. Conclusion In women of childbearing age who are scheduled to undergo LTM or LSM, the potential risk of uterine rupture on subsequent pregnancy should be explained before surgery. Pregnancy in women after myomectomy should be carefully observed, and they should be adequately counseled during this period. PMID:27896247

  7. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.

    PubMed

    O'Connell, P J; Holmes-Walker, D J; Goodman, D; Hawthorne, W J; Loudovaris, T; Gunton, J E; Thomas, H E; Grey, S T; Drogemuller, C J; Ward, G M; Torpy, D J; Coates, P T; Kay, T W

    2013-07-01

    Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.

  8. The current state of facial prosthetics – A multicenter analysis.

    PubMed

    Thiele, Oliver C; Brom, Jörn; Dunsche, Anton; Ehrenfeld, Michael; Federspil, Philippe; Frerich, Bernhard; Hölzle, Frank; Klein, Martin; Kreppel, Matthias; Kübler, Alexander C; Kübler, Norbert R; Kunkel, Martin; Kuttenberger, Johannes; Lauer, Günter; Mayer, Boris; Mohr, Christopher; Neff, Andreas; Rasse, Michael; Reich, Rudolf H; Reinert, Siegmar; Rothamel, Daniel; Sader, Robert; Schliephake, Henning; Schmelzeisen, Rainer; Schramm, Alexander; Sieg, Peter; Terheyden, Hendrik; Wiltfang, Jörg; Ziegler, Christoph M; Mischkowski, Robert A; Zöller, Joachim E

    2015-09-01

    Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

  9. [National multicenter survey: the use of intravenous antimicrobial agents].

    PubMed

    Gutiérrez Zufiaurre, M N; García-Rodríguez, J A

    2006-12-01

    Infectious diseases are currently one of the major health problems worldwide. As a consequence, both nosocomial and community-acquired infections are responsible for a significant increase in workload and health costs for hospitals, particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The use of intravenous antimicrobial agents is common in hospitalized patients. In order to determine the use of antimicrobial agents and the most frequent procedures used for their administration in Spanish hospitals, a national multicenter survey was undertaken among ICU, Internal Medicine and Surgery health staff from 63 hospitals, in which data were collected on central and peripheral catheter manipulation and intravenous administration. Results showed that, in Spain, both catheter manipulation (insertion, maintenance and removal) and administration of antimicrobial agents are performed by the nursing staff following established protocols, particularly for central catheters. Moreover, the ICUs had the highest rates of catheter-bearing patients, as well as patients undergoing antimicrobial treatment, sometimes in combination. The use of intravenous antimicrobial agents in Spanish hospitals results in an increased workload for the nursing staff and higher health costs, not to mention the risk involved with the use of vascular catheters.

  10. Multi-center airborne coherent atmospheric wind sensor (MACAWS)

    SciTech Connect

    Rothermel, J.; Menzies, R.T.; Tratt, D.M.

    1996-11-01

    The Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS) is an airborne scanning coherent Doppler lidar designed to acquire remote multi-dimensional measurements of winds and absolute aerosol backscatter in the troposphere and lower stratosphere. These measurements enable study of atmospheric dynamic processes and features at scales of motion that may be undersampled by, or may be beyond the capability of, existing or planned sensors. MACAWS capabilities enable more realistic assessments of concepts in global tropospheric wind measurement with satellite Doppler lidar, as well as a unique capability to validate the NASA Scatterometer currently scheduled for launch in late 1996. MACAWS consists of a Joule-class CO{sub 2} coherent Doppler lidar on a ruggedized optical table, a programmable scanner to direct the lidar beam in the desired direction, and a dedicated inertial navigation system to account for variable aircraft attitude and speed. MACAWS was flown for the first time in September 1995, over the eastern Pacific Ocean and western US. 33 refs., 2 figs.

  11. Cardiac bioassist: results of the French multicenter cardiomyoplasty study.

    PubMed

    Chachques, Juan C; Jegaden, Olivier; Mesana, Thierry; Glock, Yves; Grandjean, Pierre A; Carpentier, Alain F

    2009-12-01

    The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic (48%), idiopathic (45%) or other (7%). Cardiomyoplasty was performed using the latissimus dorsi muscle which was electrostimulated after surgery. During follow-up, 88% of patients improved clinically. Hospital death occurred in 29 (14%) patients and was related to the severity of preoperative heart failure symptoms. Late mortality occurred in 99 patients due to heart failure (44%), sudden death (37%), or noncardiac causes (18%). Combined dynamic cardiomyoplasty and implantation of a cardiac rhythm management system was safely achieved in 22 patients, and 26 underwent heart transplantation for recurrent heart failure. Long-term functional improvements were observed in most patients, and the best outcome was achieved in those with isolated right ventricular failure. Dynamic cardiomyoplasty can be considered as a destination therapy or a mid- to long-term biological bridge to heart transplantation.

  12. Comprehensive assessment of long-term effects of reducing intake of energy phase 2 (CALERIE Phase 2) screening and recruitment: Methods and results

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized con...

  13. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    PubMed Central

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, p<0.001). Moreover, 51.0% of participants experienced a response at week 12. Premature discontinuation of blonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Conclusion Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP. PMID:27482249

  14. Regional Gray Matter Atrophy in Relapsing Remitting Multiple Sclerosis: Baseline Analysis of Multi-Center Data

    PubMed Central

    Datta, Sushmita; Staewen, Terrell D.; Cofield, Stacy S.; Cutter, Gary R.; Lublin, Fred D.; Wolinsky, Jerry S.; Narayana, Ponnada A.

    2015-01-01

    Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson’s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r = −0.133; p < 0.001) and DD (r = −0.098; p = 0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r = −0.492; p-value < 0.001), T1 LL (r = −0.473; p-value < 0.001) and nCSF (r = −0.367; p-value < 0.001). PMID:25787188

  15. Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

    PubMed Central

    Tura, Bernardo R; Martino, Helena F; Gowdak, Luis H; dos Santos, Ricardo Ribeiro; Dohmann, Hans F; Krieger, José E; Feitosa, Gilson; Vilas-Boas, Fábio; Oliveira, Sérgio A; Silva, Suzana A; Bozza, Augusto Z; Borojevic, Radovan; de Carvalho, Antonio C Campos

    2007-01-01

    Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT

  16. Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

    PubMed Central

    Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

    2011-01-01

    Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

  17. A modular informatics platform for effective support of collaborative and multicenter studies in cardiology.

    PubMed

    Marinelli, Martina; Positano, Vincenzo; Lorenzoni, Valentina; Caselli, Chiara; Mangione, Maurizio; Marcheschi, Paolo; Puzzuoli, Stefano; Esposito, Natalia; L'Abbate, Giuseppe Andrea; Neglia, Danilo

    2016-12-01

    Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease.

  18. Research priorities for a multi-center child abuse pediatrics network - CAPNET.

    PubMed

    Lindberg, Daniel M; Wood, Joanne N; Campbell, Kristine A; Scribano, Philip V; Laskey, Antoinette; Leventhal, John M; Pierce, Mary Clyde; Runyan, Desmond K

    2017-03-01

    Although child maltreatment medical research has benefited from several multi-center studies, the new specialty of child abuse pediatrics has not had a sustainable network capable of pursuing multiple, prospective, clinically-oriented studies. The Child Abuse Pediatrics Network (CAPNET) is a new multi-center research network dedicated to child maltreatment medical research. In order to establish a relevant, practical research agenda, we conducted a modified Delphi process to determine the topic areas with highest priority for such a network. Research questions were solicited from members of the Ray E. Helfer Society and study authors and were sorted into topic areas. These topic areas were rated for priority using iterative rounds of ratings and in-person meetings. The topics rated with the highest priority were missed diagnosis and selected/indicated prevention. This agenda can be used to target future multi-center child maltreatment medical research.

  19. Managing Multi-center Flow Cytometry Data for Immune Monitoring.

    PubMed

    White, Scott; Laske, Karoline; Welters, Marij Jp; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21-23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables automated

  20. Managing Multi-center Flow Cytometry Data for Immune Monitoring

    PubMed Central

    White, Scott; Laske, Karoline; Welters, Marij JP; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1–5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21–23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables

  1. Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

    NASA Astrophysics Data System (ADS)

    Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; McCaul, E. W., Jr.

    1993-01-01

    This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall

  2. The Multi-center Airborne Coherent Atmospheric Wind Sensor.

    NASA Astrophysics Data System (ADS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James N.; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1998-04-01

    In 1992 the atmospheric lidar remote sensing groups of the National Aeronautics and Space Administration Marshall Space Flight Center, the National Oceanic and Atmospheric Administration/Environmental Technology Laboratory (NOAA/ETL), and the Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in three-dimensional volumes in the troposphere and lower stratosphere.A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise that were developed for previous atmospheric research by the respective institutions. For example, the laser transmitter is that of the mobile ground-based Doppler lidar system developed and used in atmospheric research for more than a decade at NOAA/ETL.The motivation for MACAWS is threefold: 1) to obtain fundamental measurements of subsynoptic-scale processes and features to improve subgrid-scale parameterizations in large-scale models, 2) to obtain datasets in order to improve the understanding of and predictive capabilities for meteorological systems on subsynoptic scales, and 3) to validate (simulate) the performance of existing (planned) satellite-borne sensors.Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following system improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  3. Influenza vaccination coverage among medical residents: an Italian multicenter survey.

    PubMed

    Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele

    2014-01-01

    Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

  4. Multicenter Comparison of Seven 25OH Vitamin D Automated Immunoassays

    PubMed Central

    Lippi, Giuseppe; Salvagno, Gian Luca; Fortunato, Antonio; Dipalo, Mariella; Aloe, Rosalia; Da Rin, Giorgio; Giavarina, Davide

    2015-01-01

    Summary Background The measurement of 25OH vitamin D continues to grow in clinical laboratories. The aim of this multi-center study was to compare the results of seven automated commercial immunoassays with a reference HPLC technique. Methods One hundred and twenty consecutive outpatient serum samples were centrifuged, divided in aliquots, frozen and shipped to the participating laboratories. 25OH Vitamin D was measured with a reference HPLC system and with seven automated commercial immunoassays (Roche Cobas E601, Beckman Coulter Unicel DXI 800, Ortho Vitros ES, DiaSorin Liaison, Siemens Advia Centaur, Abbott Architect i System and IDS iSYS). Results Compared to the reference method, the regression coefficients ranged from 0.923 to 0.961 (all p<0.001). The slope of Deming fit ranged from 0.95 to 1.06, whereas the intercept was comprised between −15.2 and 9.2 nmol/L. The bias from the reference HPLC technique varied from −14.5 to 8.7 nmol/L. The minimum performance goal for bias was slightly exceeded by only one immunoassay. The agreement between HPLC and the different immunoassays at 50 nmol/L 25OH Vitamin D varied between 0.61 and 0.85 (all p<0.001). The percentage of samples below this cut-off was significantly different with only one immunoassay. Conclusions The excellent correlation with the reference HPLC technique attests that all seven automated immunoassays may be reliably used for routine assessment of 25OH-D in clinical laboratories. The significant bias among the different methods seems mostly attributable to the lack of standardization and calls for additional efforts for improving harmonization of 25OH-D immunoassays. PMID:28356846

  5. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study

    PubMed Central

    Halbach, Nicky; Julu, Peter; Witt‐Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F.; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-01-01

    Many studies have attempted to establish the genotype–phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well‐defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype–phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non‐invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence‐based management in RTT. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:27354166

  6. Reducing between scanner differences in multi-center PET studies.

    PubMed

    Joshi, Aniket; Koeppe, Robert A; Fessler, Jeffrey A

    2009-05-15

    This work is part of the multi-center Alzheimer's Disease Neuroimaging Initiative (ADNI), a large multi-site study of dementia, including patients having mild cognitive impairment (MCI), probable Alzheimer's disease (AD), as well as healthy elderly controls. A major portion of ADNI involves the use of [(18)F]-fluorodeoxyglucose (FDG) with positron emission tomography (PET). The objective of this paper is the reduction of inter-scanner differences in the FDG-PET scans obtained from the 50 participating PET centers having fifteen different scanner models. In spite of a standardized imaging protocol, systematic inter-scanner variability in PET images from various sites is observed primarily due to differences in scanner resolution, reconstruction techniques, and different implementations of scatter and attenuation corrections. Two correction steps were developed by comparison of 3-D Hoffman brain phantom scans with the 'gold standard' digital 3-D Hoffman brain phantom: i) high frequency correction; where a smoothing kernel for each scanner model was estimated to smooth all images to a common resolution and ii) low frequency correction; where smooth affine correction factors were obtained to reduce the attenuation and scatter correction errors. For the phantom data, the high frequency correction reduced the variability by 20%-50% and the low frequency correction further reduced the differences by another 20%-25%. Correction factors obtained from phantom studies were applied to 95 scans from normal control subjects obtained from the participating sites. The high frequency correction reduced differences similar to the phantom studies. However, the low frequency correction did not further reduce differences; hence further refinement of the procedure is necessary.

  7. The Global Enteric Multicenter Study (GEMS): Impetus, Rationale, and Genesis

    PubMed Central

    Levine, Myron M.; Kotloff, Karen L.; Nataro, James P.; Muhsen, Khitam

    2012-01-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12 600 analyzable cases and 12 600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467 000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease. PMID:23169934

  8. The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis.

    PubMed

    Levine, Myron M; Kotloff, Karen L; Nataro, James P; Muhsen, Khitam

    2012-12-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12,600 analyzable cases and 12,600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467,000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease.

  9. A Multicenter Reference Intervals Study for Specific Proteins in China

    PubMed Central

    Qin, Xuzhen; Tang, Guodong; Qiu, Ling; Li, Peng Chang; Xia, Liangyu; Chen, Ming; Tao, Zhihua; Li, Shijun; Liu, Min; Wang, Liang; Gao, Shang; Yu, Songlin; Cheng, Xinqi; Han, Jianhua; Hou, Li’an; Kawano, Reo; Ichihara, Kiyoshi

    2015-01-01

    Abstract A multicenter study conducted in healthy population of 6 cities from the 4 corners and central China for 7 serum-specific proteins to identify the sources of variation and establish the reference intervals on 2 automation platforms. A total of 3148 subjects aged 19 to 64 years old were enrolled in this study to ensure at least 120 participants in each 10-year age group and each city. The majority of samples were transported to central laboratory and measured on both Beckman AU5800 and Immage 800 analytical systems. Three-level nested ANOVA, multiple regression analysis, and the scatter plot were used to explore the variations from sex, age, region, BMI, cigarette smoking, and so on. The latent abnormal value exclusion (LAVE) method was applied at the time of computing RIs as a method for secondary exclusion. Regionality was not observed in any of the immunoassay in China. Variations for sex were significant for IgM among the immune analytes. For CRP and hsCRP results with turbidimetry method (Beckman Coulter AU5800) were lower than the nephelometry method (Beckman Immage). The LAVE method did not affect the RIs computed for the majority of analytes except C4, CRP, and hsCRP. In the scatter plot at the age of 45 years old C3, C4, and IgM reached an inflection point, accordingly RIs were separated by the age group. With the lack of regional differences and the well-standardized status of test results, the RIs of C3, IgG, IgA, IgM derived from this nationwide study can be used for the entire Chinese population. C4, CRP, and hsCRP were affected by different platforms and gender was a significant source of variation for IgM, so they had separated RIs. PMID:26656356

  10. WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: Results of an open label, non-comparative, multi-centric, post marketing observational study

    PubMed Central

    Kumbla, D.K.; Kumar, S.; Reddy, Y.V.; Trailokya, A.; Naik, M.

    2014-01-01

    Background Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. Objective To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. Material and methods An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to <140 mmHg and diastolic BP (DBP) to <90 mmHg at 3 and 6 months after initiation of treatment with olmesartan. All reported adverse events were recorded. Results A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p < 0.0001) with olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Conclusion Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. PMID:24973841

  11. Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation.

    PubMed

    Alexander, B D; Dodds Ashley, E S; Addison, R M; Alspaugh, J A; Chao, N J; Perfect, J R

    2006-03-01

    Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.

  12. Analytically reduced form of multicenter integrals from Gaussian transforms. [in atomic and molecular physics

    NASA Technical Reports Server (NTRS)

    Straton, Jack C.

    1989-01-01

    The four-dimensional Fourier-Feynman transformations previously used in analytically reducing the general class of integrals containing multicenter products of 1s hydrogenic orbitals, Coulomb or Yukawa potentials, and plane waves, are replaced by the one-dimensional Gaussian transformation. This reduces the previously required double-diagonalization of the quadratic form of the multicenter integrals to only one diagonalization, yielding a simpler reduced form of the integral. The present work also extends the result to include all s states and pairs of states with l not equal to zero summed over the m quantum number.

  13. Detection of hepatocellular carcinoma and liver metastases with BR14: a multicenter phase IIA study.

    PubMed

    Hohmann, Joachim; Müller, Anja; Skrok, Jan; Wolf, Karl-Jürgen; Martegani, Alberto; Dietrich, Christoph F; Albrecht, Thomas

    2012-03-01

    The study was designed primarily to find the optimal dosage range of BR14 contrast-enhanced ultrasonography (CEUS) to detect malignant focal liver lesions. Secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced MRI (CE MRI). We studied 25 patients (9 females, 16 males, mean age, 66 years) with known hepatocellular carcinoma or liver metastases at 3 centers over a 3-month period. Each patient underwent a baseline examination and at least 3 CEUS examinations with ascending dose levels (0.25 mL; 1.0 mL; 4.0 mL) of BR14. CE MRI was performed 4 weeks before or after the CEUS examination. Dedicated liver maps were used to record the location, size, and type of detected lesions. Examination quality was documented and safety parameters were assessed. The number of lesions detected by BR14 CEUS increased with dosage, whereas the number of missed lesions and the lesion sizes decreased. Despite the increasing contrast enhancement, substantial differences among dosages were not seen for other image quality parameters. No significant changes were noted in safety parameters and no serious adverse events were reported. We conclude that the recommended dose level of BR14 is between 1 mL and 4 mL; at this dosage, lesion detection is comparable to that of CE MRI.

  14. NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research

    PubMed Central

    Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D

    2015-01-01

    Background A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. Objective This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. Methods NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f 1, f 2, ..., f k. The input for each function f i has 3 components: a random number r, an integer n, and input data m. The result, f i(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f 1(r 1, n 1, m 1), f 2(r 2, n 2, m 2), ..., f k(r k, n k, m k). In the second phase, the intermediate string generated in Phase 1 is encrypted

  15. A Multicenter Evaluation of Blood Culture Practices, Contamination Rates, and the Distribution of Causative Bacteria

    PubMed Central

    Altindis, Mustafa; Koroglu, Mehmet; Demiray, Tayfur; Dal, Tuba; Ozdemir, Mehmet; Sengil, Ahmet Zeki; Atasoy, Ali Riza; Doğan, Metin; Cicek, Aysegul Copur; Ece, Gulfem; Kaya, Selcuk; Iraz, Meryem; Gultepe, Bilge Sumbul; Temiz, Hakan; Kandemir, Idris; Aksaray, Sebahat; Cetinkol, Yeliz; Sahin, Idris; Guducuoglu, Huseyin; Kilic, Abdullah; Kocoglu, Esra; Gulhan, Baris; Karabay, Oguz

    2016-01-01

    Background: The prognostic value of blood culture testing in the diagnosis of bacteremia is limited by contamination. Objectives: In this multicenter study, the aim was to evaluate the contamination rates of blood cultures as well as the parameters that affect the culture results. Materials and Methods: Sample collection practices and culture data obtained from 16 university/research hospitals were retrospectively evaluated. A total of 214,340 blood samples from 43,254 patients admitted to the centers in 2013 were included in this study. The blood culture results were evaluated based on the three phases of laboratory testing: the pre-analytic, the analytic, and the post-analytic phase. Results: Blood samples were obtained from the patients through either the peripheral venous route (64%) or an intravascular catheter (36%). Povidone-iodine (60%) or alcohol (40%) was applied to disinfect the skin. Of the 16 centers, 62.5% have no dedicated phlebotomy team, 68.7% employed a blood culture system, 86.7% conducted additional studies with pediatric bottles, and 43.7% with anaerobic bottles. One center maintained a blood culture quality control study. The average growth rate in the bottles of blood cultures during the defined period (1259 - 26,400/year) was 32.3%. Of the growing microorganisms, 67% were causative agents, while 33% were contaminants. The contamination rates of the centers ranged from 1% to 17%. The average growth time for the causative bacteria was 21.4 hours, while it was 36.3 hours for the contaminant bacteria. The most commonly isolated pathogens were Escherichia coli (22.45%) and coagulase-negative staphylococci (CoNS) (20.11%). Further, the most frequently identified contaminant bacteria were CoNS (44.04%). Conclusions: The high contamination rates were remarkable in this study. We suggest that the hospitals’ staff should be better trained in blood sample collection and processing. Sterile glove usage, alcohol usage for disinfection, the presence of

  16. Management of Pneumothorax in Emergency Medicine Departments: Multicenter Trial

    PubMed Central

    Ince, Abdulkadir; Ozucelik, Dogac Niyazi; Avci, Akkan; Nizam, Ozgur; Dogan, Halil; Topal, Mehmet Ali

    2013-01-01

    Background: Pneumothorax is common and life-threatening clinical condition which may require emergency treatment in Emergency Medicine Departments. Objectives: We aimed to reveal the epidemiological analysis of the patients admitted to the Emergency Department with pneumothorax. Material and Methods: This case-control and multi-center study was conducted in the patients treated with the diagnosis of pneumothorax between 01.01.2010-31.12.2010. Patient data were collected from hospital automation system. According to the etiology of the pneumothorax, study groups were arranged like spontaneous pneumothorax and traumatic pneumothorax. Results: 82.2% (n = 106) of patients were male and 17.8% (n = 23) of patients were female and mean age were 31.3 ± 20,2 (Minimum: 1, Maximum: 87). 68.2% (n = 88) of patients were spontaneous pneumothorax (61.36%, n=79 were primary spontaneous pneumothorax) and 31.8% (n = 41) of patients were traumatic pneumothorax (21.95% were iatrogenic pneumothorax). Main complaint is shortness of breath (52.3%, n=67) and 38% (n=49) of patients were smokers. Posteroanterior (PA) Chest X-Ray has been enough for 64.3% (n = 83) of the patients' diagnosis. Tube thoracostomy is applied to 84.5% (n = 109) of patients and surgery is applied to 9.3% (n = 12) of patients and 6.2% (n = 8) of patients were discharged with conservative treatment. Spontaneous pneumothorax showed statistically significant high recurrence compared with traumatic pneumothorax (P = 0.007). 4.65% of (n = 6) patients died. The average age of those who died (9.3 ± 19.9), statistically were significantly lower the mean age of living patients (32.4 ± 19.7) (t test, P = 0,006). 83.33% of the patients who died were neonatals and in the 0-1 years age group, and five of these patients were secondary spontaneous pneumothorax, and one of these patients were iatrogenic pneumothorax due to mechanical ventilation. Conclusions: Pneumothorax in adults can be treated by tube thoracostomy or

  17. Prospective Multicenter Study of Children With Bronchiolitis Requiring Mechanical Ventilation

    PubMed Central

    Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Forgey, Tate F.; Clark, Sunday; Espinola, Janice A.; Camargo, Carlos A.

    2012-01-01

    OBJECTIVE: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS: There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7–11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1–1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0–2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2–2.1), presence of apnea (OR 4.8; 95% CI 2.5–8.5), inadequate oral intake (OR 2.5; 95% CI 1.3–4.3), severe retractions (OR 11.1; 95% CI 2.4–33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0–4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began. PMID:22869823

  18. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  19. [Use of amantadine sulfate (PK-MERZ) during emergence from coma: results of a multicenter study].

    PubMed

    Belkin, A A; Shchegolev, A V; Kondrat'ev, A N; Bubnova, I D

    2008-01-01

    The paper gives the results of the first multicenter study of the efficiency of using amantadine sulfate (PK-Merz) in patients with acute cerebral disease during coma emergence. The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease. Full objectivism of the findings requires further studies.

  20. Holmium:YAG laser coronary angioplasty: results of a multicenter registry

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1994-07-01

    To date, 1201 symptomatic patients with significant coronary artery disease were treated with the mid IR holmium:YAG (2.1 micron) laser in a multicenter study. Updated results of this study, as presented herein, substantiate the important role of this laser in treatment of lesions not ideal for conventional balloon angioplasty. This device is a safe and effective means of coronary revascularization.

  1. Enhanced Pair Production in Multicenter Systems by SuperIntense Lasers

    NASA Astrophysics Data System (ADS)

    Bandrauk, Andre

    2014-03-01

    Electron-positron(e-e +) pair production is considered for many-center systems with multiple bare nuclei immersed in intense static electric fields corresponding to the extrema of electric fields planned by future super intense laser pulse sources with intensities I > 1024 W/cm2. It is shown analytically using an exactly solvable 1-D delta potential model in a multicenter Dirac equation that there are two distinct regimes where pair production rates are enhanced.At small internuclear distances, the effective nuclear charge approaches the critical charge where the ground state dives into the negative continuum of the Dirac equation. At large atomic distances a new mechanism is predicted, similar to Charge Resonance Enhanced Ionization of molecules by intense, I ~ 1024 W/cm2, laser pulses. Multicenter resonances from the negative energy states are shown to cross into the positive energy states due to large field induced Stark shifts thus resulting in a resonantly enhanced pair production mechanism. A numerical method is developed to calculate the pair production rates from the multicenter Dirac equation. The latter is evaluated for systems (clusters) up to five nuclei of large charge. It is shown that the pair production rate for multicenter systems in superintense electric fields generally exceeds by orders of magnitudes the Schwinger tunneling rate which requires intensities of ~ 1029 W''/cm2. Funded by Canada Research Chair Program.

  2. Who Donates Their Body to Science? An International, Multicenter, Prospective Study

    ERIC Educational Resources Information Center

    Cornwall, Jon; Perry, Gary F.; Louw, Graham; Stringer, Mark D.

    2012-01-01

    The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of…

  3. MULTI-CENTER PRECISION OF CORTICAL AND TRABECULAR BONE QUALITY MEASURES ASSESSED BY HR-PQCT

    PubMed Central

    Burghardt, Andrew J.; Pialat, Jean-Baptiste; Kazakia, Galateia J.; Boutroy, Stephanie; Engelke, Klaus; Patsch, Janina M.; Valentinitsch, Alexander; Liu, Danmei; Szabo, Eva; Bogado, Cesar E.; Zanchetta, Maria Belen; McKay, Heather A.; Shane, Elizabeth; Boyd, Steven K.; Bouxsein, Mary L.; Chapurlat, Roland; Khosla, Sundeep; Majumdar, Sharmila

    2012-01-01

    High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technique to address important skeletal health questions requires translation to standardized multi-center data pools. Our goal was to evaluate the feasibility of pooling data in multi-center HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short (<72hrs), intermediate (3–5mo), and long-term intervals (28mo). Multi-center precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were <1% for all parameters except Ct.Th (1.1%), Ct.Th.SD (2.6%), Tb.Sp.SD (1.8%), and porosity measures (6–8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7–2.0%; p < 0.05 vs. short-term) and several structure measures: Ct.Th (3.4%; p < 0.01 vs. short-term), Ct.Po (15.4%; p < 0.01 vs. short-term), and Tb.Th (2.2%; p < 0.01 vs. short-term). Multi-center RMSCVs were also significantly higher than short-term values: 2–4% for density and µFE measures (p < 0.0001), 2.6–5.3% for morphometric measures (p < 0.001), while Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multi-center precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multi-center precision was comparable to previously reported in vivo single-center precision errors, although this was approximately 2–5 times worse than ex vivo short

  4. A multicenter prospective cohort study of volume management after subarachnoid hemorrhage: circulatory characteristics of pulmonary edema after subarachnoid hemorrhage.

    PubMed

    Obata, Yoshiki; Takeda, Junichi; Sato, Yohei; Ishikura, Hiroyasu; Matsui, Toru; Isotani, Eiji

    2016-08-01

    OBJECT Subarachnoid hemorrhage (SAH) is often accompanied by pulmonary complications, which may lead to poor outcomes and death. This study investigated the incidence and cause of pulmonary edema in patients with SAH by using hemodynamic monitoring with PiCCO-plus pulse contour analysis. METHODS A total of 204 patients with SAH were included in a multicenter prospective cohort study to investigate hemodynamic changes after surgical clipping or coil embolization of ruptured cerebral aneurysms by using a PiCCO-plus device. Changes in various hemodynamic parameters after SAH were analyzed statistically. RESULTS Fifty-two patients (25.5%) developed pulmonary edema. Patients with pulmonary edema (PE group) were significantly older than those without pulmonary edema (non-PE group) (p = 0.017). The mean extravascular lung water index was significantly higher in the PE group than in the non-PE group throughout the study period. The pulmonary vascular permeability index (PVPI) was significantly higher in the PE group than in the non-PE group on Day 6 (p = 0.029) and Day 10 (p = 0.011). The cardiac index of the PE group was significantly decreased biphasically on Days 2 and 10 compared with that of the non-PE group. In the early phase (Days 1-5 after SAH), the daily water balance of the PE group was slightly positive. In the delayed phase (Days 6-14 after SAH), the serum C-reactive protein level and the global end-diastolic volume index were significantly higher in the PE group than in the non-PE group, whereas the PVPI tended to be higher in the PE group. CONCLUSIONS Pulmonary edema that occurs in the early and delayed phases after SAH is caused by cardiac failure and inflammatory (i.e., noncardiogenic) conditions, respectively. Measurement of the extravascular lung water index, cardiac index, and PVPI by PiCCO-plus monitoring is useful for identifying pulmonary edema in patients with SAH.

  5. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life.

    PubMed

    Saccardi, Riccardo; Mancardi, Gian Luigi; Solari, Alessandra; Bosi, Alberto; Bruzzi, Paolo; Di Bartolomeo, Paolo; Donelli, Amedea; Filippi, Massimo; Guerrasio, Angelo; Gualandi, Francesca; La Nasa, Giorgio; Murialdo, Alessandra; Pagliai, Francesca; Papineschi, Federico; Scappini, Barbara; Marmont, Alberto M

    2005-03-15

    Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.

  6. Multicenter clinical trials in sepsis: understanding the big picture and building a successful operation at your hospital.

    PubMed

    Dellinger, R Phillip; Schorr, Christa; Trzeciak, Stephen

    2011-03-01

    Only through adequately designed and adequately conducted clinical trials can new treatments be found for the benefit of the septic patient. Over the past 20 years, tens of thousands of patients have been enrolled in sepsis clinical trials with little success. These efforts, however, have not been without worth. Much has been learned and the knowledge gained has changed our approach to trial design in this very difficult field. Animal studies are better designed to match the clinical picture of severe sepsis. Phase II studies are more carefully engineered to answer questions about the most suitable target population and end points. Trial conduct likely benefits from use of CROs and a CCC. The future of clinical trials may include more standardization of sepsis management across investigative sites. Before the decision is made to become an investigative site in a multicenter industry-sponsored clinical trial in sepsis or severe sepsis, it is important to recognize what is required to succeed. Once these key-to-success elements are in place, members of the investigative team are more likely to realize the satisfaction and career growth from becoming a successful site. The most professional satisfaction comes from the knowledge of contributing to original science in the field of the sepsis.

  7. A new design of a polysomnography-based multi-center treatment study for the restless legs syndrome.

    PubMed

    Penzel, T; Brandenburg, U; Peter, J H; Otto, R; Hundemer, H P; Lledo, A; Wetter, T C; Trenkwalder, C

    2002-04-01

    Periodic limb movements (PLM) cause sleep disorders and daytime symptoms and are frequently associated with restless legs syndrome (RLS). Treatment of RLS with increased PLM during sleep (PLMS) has been evaluated in studies limited in size, methodology and study length. This long-term, placebo-controlled, multi-center, study with polysomnography (PSG) recordings has been designed in order to assess efficacy and safety parameters of pergolide treatment in RLS. This novel approach for a study was created to assure consistently high quality of sleep recording and analysis. Using defined criteria, 21 sleep centers were approved for the study after a pilot phase. Seventeen centers with 16 different PSG systems randomized 100 patients. Digital sleep recordings from 4 visits (baseline, 6 weeks, 6 months, 1 year) were submitted to one central evaluation center following previously defined standardized operating procedures. Visual scoring of all recordings was performed by one independent scorer. Reliability of scoring was evaluated for 20 randomly selected baseline recordings. The mean epoch by epoch agreement for sleep stages was 88% (range 81-96%), mean arousal re-scoring differed by 0.5 (range: -16 to 20), and mean PLM index re-scoring differed by 0.1 (range: -1.5 to 2.1). Using one scorer with a demonstrated high reliability in PSG scoring for all sleep recordings was very effective in terms of study cost, study duration, and data quality.

  8. Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study

    PubMed Central

    Bosca-Watts, Marta Maia; Cortes, Xavier; Iborra, Marisa; Huguet, Jose Maria; Sempere, Laura; Garcia, Gloria; Gil, Rafa; Garcia, MariFe; Muñoz, Marga; Almela, Pedro; Maroto, Nuria; Paredes, Jose Maria

    2016-01-01

    AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response. METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at week 0 and 14 with the physician’s global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database. RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naïve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at week 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at week 14. Being anti-TNF treatment naïve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of follow-up. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted. CONCLUSION This real-life practice study endorses golimumab’s promising results, demonstrating its short-term effectiveness and confirming

  9. A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2)

    PubMed Central

    2012-01-01

    Background Computed tomography (CT) scanning has become essential in the early diagnostic phase of trauma care because of its high diagnostic accuracy. The introduction of multi-slice CT scanners and infrastructural improvements made total-body CT scanning technically feasible and its usage is currently becoming common practice in several trauma centers. However, literature provides limited evidence whether immediate total-body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total-body CT scanning in trauma patients. Methods/design The REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. Patients in whom direct scanning will hamper necessary cardiopulmonary resuscitation or who require an immediate operation because of imminent death (both as judged by the trauma team leader) are excluded. Randomization will be computer assisted. The intervention group will receive a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness. Discussion The REACT-2 trial is a multicenter randomized clinical trial that will provide evidence on the value of immediate total-body CT scanning during the primary

  10. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  11. Multicenter airborne coherent atmospheric wind sensor (MACAWS) instrument: recent upgrades and results

    NASA Astrophysics Data System (ADS)

    Howell, James N.; Rothermel, Jeffrey; Tratt, David M.; Cutten, Dean; Darby, Lisa S.; Hardesty, R. Michael

    1999-10-01

    The Multicenter Airborne Coherent Atmospheric Wind Sensor instrument is an airborne coherent Doppler laser radar (Lidar) capable of measuring atmospheric wind fields and aerosol structure. Since the first demonstration flights onboard the NASA DC-8 research aircraft in September 1995, two additional science flights have been completed. Several system upgrades have also bee implemented. In this paper we discuss the system upgrades and present several case studies which demonstrate the various capabilities of the system.

  12. Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1: A Multicenter Project With 3 Clinical Trials

    DTIC Science & Technology

    2006-06-01

    Tumors in Neurofibromatosis Type 1: A Multicenter Project with 3 Clinical Trials PRINCIPAL INVESTIGATOR: David Viskochil, M.D., Ph.D...Trials 5b. GRANT NUMBER W81XWH-04-1-0502 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Viskochil, M.D., Ph.D. 5d. PROJECT...submission of a clinical trial for neoadjuvant chemotherapy in MPNST (DAMD-NF043129; PI- David Viskochil). This proposal was not funded, however it was

  13. Feasibility and variability of measuring the Lung Clearance Index in a multi-center setting.

    PubMed

    Fuchs, Susanne I; Ellemunter, Helmut; Eder, Johannes; Mellies, Uwe; Grosse-Onnebrink, Jörg; Tümmler, Burkhard; Staab, Doris; Jobst, Andrea; Griese, Matthias; Ripper, Jan; Rietschel, Ernst; Zeidler, Susanne; Ahrens, Frank; Gappa, Monika

    2012-07-01

    The Lung Clearance Index (LCI) is superior to spirometry in detecting early lung disease in cystic fibrosis (CF) and correlates with structural lung changes seen on CT scans. The LCI has the potential to become a novel outcome parameter for clinical and research purposes. However longitudinal studies are required to further prove its prognostic value. Multi-center design is likely to facilitate realization of such studies. Therefore the aim of the present study was to assess multi-center feasibility and inter-center variability of LCI measurements in healthy children and adolescents. Comparative measurements were performed in unselected patients with CF to confirm previous single-center results. LCI measurements were performed in eight centers using the EasyOne Pro, MBW Module (ndd Medical Technologies, Zurich, Switzerland). The overall success rate for LCI measurements was 75.5%, leaving 102/151 measurements in healthy volunteers and 139/183 measurements in patients with CF for final analysis. Age ranged between 4 and 24 years. Mean LCI (range of means among centers) was 6.3 (6.0-6.5) in healthy volunteers and thus normal. Inter-center variability of center means was 2.9%, ANOVA including Schffé procedure demonstrated no significant inter-center differences (P > 0.05). Mean LCI (range of means among centers) was 8.2 (7.4-8.9) in CF and thus abnormal. Our study demonstrates good multi-center feasibility and low inter-center variability of the LCI in healthy volunteers when measured with the EasyOne Pro MBW module. Our data confirm published LCI data in CF. However, central coordination, quality control, regular training, and supervision during the entire study appear essential for successfully performing multi-center trials.

  14. Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

    SciTech Connect

    Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

    2013-10-01

    Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

  15. LORIS: a web-based data management system for multi-center studies

    PubMed Central

    Das, Samir; Zijdenbos, Alex P.; Harlap, Jonathan; Vins, Dario; Evans, Alan C.

    2012-01-01

    Longitudinal Online Research and Imaging System (LORIS) is a modular and extensible web-based data management system that integrates all aspects of a multi-center study: from heterogeneous data acquisition (imaging, clinical, behavior, and genetics) to storage, processing, and ultimately dissemination. It provides a secure, user-friendly, and streamlined platform to automate the flow of clinical trials and complex multi-center studies. A subject-centric internal organization allows researchers to capture and subsequently extract all information, longitudinal or cross-sectional, from any subset of the study cohort. Extensive error-checking and quality control procedures, security, data management, data querying, and administrative functions provide LORIS with a triple capability (1) continuous project coordination and monitoring of data acquisition (2) data storage/cleaning/querying, (3) interface with arbitrary external data processing “pipelines.” LORIS is a complete solution that has been thoroughly tested through a full 10 year life cycle of a multi-center longitudinal project1 and is now supporting numerous international neurodevelopment and neurodegeneration research projects. PMID:22319489

  16. Multicenter surveillance of species distribution and antifungal susceptibilities of Candida bloodstream isolates in South Korea.

    PubMed

    Jung, Sook-In; Shin, Jong Hee; Song, Jae-Hoon; Peck, Kyong Ran; Lee, Kyungwon; Kim, Mi-Na; Chang, Hyun Ha; Moon, Chi Sook

    2010-06-01

    Multicenter data on in vitro susceptibility of Candida bloodstream isolates to echinocandin antifungal agents is still lacking in South Korea. We performed a prospective multicenter study to determine the species distribution of Candida bloodstream isolates and their susceptibility to five antifungal agents, including caspofungin and micafungin. A total of 639 isolates were collected from 20 tertiary hospitals between September 2006 and August 2007. Antifungal susceptibilities were determined through the use of the CLSI broth microdilution method M27-A3. The overall species distribution was as follows; Candida albicans (38%), Candida parapsilosis (26%), Candia tropicalis (20%), Candida glabrata (11%), and miscellaneous Candida species (5%). Although C. parapsilosis and miscellaneous Candida species were less susceptible to both echinocandins, all 639 isolates were susceptible to both caspofungin and micafungin (MIC, multicenter candidemia study conducted in South Korea and shows that non-C. albicans Candida species, including C. parapsilosis, constitutes over 60% of all Candida species isolates recovered from the bloodstream. In addition, the rates of resistance to all five antifungals, including two echinocandins, are still low among bloodstream isolates in South Korea.

  17. Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

    NASA Technical Reports Server (NTRS)

    Landry, Steven J.; Farley, Todd; Hoang, Ty

    2005-01-01

    Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

  18. Laparoscopic Radiofrequency Fibroid Ablation: Phase II and Phase III Results

    PubMed Central

    Pemueller, Rodolfo Robles; Garza Leal, José Gerardo; Abbott, Karen R.; Falls, Janice L.; Macer, James

    2014-01-01

    Background and Objectives: To review phase II and phase III treatments of symptomatic uterine fibroids (myomas) using laparoscopic radiofrequency volumetric thermal ablation (RFVTA). Methods: We performed a retrospective, multicenter clinical analysis of 206 consecutive cases of ultrasound-guided laparoscopic RFVTA of symptomatic myomas conducted on an outpatient basis under two phase II studies at 2 sites (n = 69) and one phase III study at 11 sites (n = 137). Descriptive and exploratory, general trend, and matched-pair analyses were applied. Results: From baseline to 12 months in the phase II study, the mean transformed symptom severity scores improved from 53.9 to 8.8 (P < .001) (n = 57), health-related quality-of-life scores improved from 48.5 to 92.0 (P < .001) (n = 57), and mean uterine volume decreased from 204.4 cm3 to 151.4 cm3 (P = .008) (n = 58). Patients missed a median of 4 days of work (range, 2–10 days). The rate of possible device-related adverse events was 1.4% (1 of 69). In the phase III study, approximately 98% of patients were assessed at 12 months, and their transformed symptom severity scores, health-related quality-of-life scores, mean decrease in uterine volume, and mean menstrual bleeding reduction were also significant. Patients in phase III missed a median of 5 days of work (range, 1–29 days). The rate of periprocedural device-related adverse events was 3.5% (5 of 137). Despite the enrollment requirement for patients in both phases to have completed childbearing, 4 pregnancies occurred within the first year after treatment. Conclusions: RFVTA does not require any uterine incisions and provides a uterine-sparing procedure with rapid recovery, significant reduction in uterine size, significant reduction or elimination of myoma symptoms, and significant improvement in quality of life. PMID:24960480

  19. Phases and Phase Transitions

    NASA Astrophysics Data System (ADS)

    Gitterman, Moshe

    2014-09-01

    In discussing phase transitions, the first thing that we have to do is to define a phase. This is a concept from thermodynamics and statistical mechanics, where a phase is defined as a homogeneous system. As a simple example, let us consider instant coffee. This consists of coffee powder dissolved in water, and after stirring it we have a homogeneous mixture, i.e., a single phase. If we add to a cup of coffee a spoonful of sugar and stir it well, we still have a single phase -- sweet coffee. However, if we add ten spoonfuls of sugar, then the contents of the cup will no longer be homogeneous, but rather a mixture of two homogeneous systems or phases, sweet liquid coffee on top and coffee-flavored wet sugar at the bottom...

  20. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial

    PubMed Central

    Levkovitz, Yechiel; Isserles, Moshe; Padberg, Frank; Lisanby, Sarah H; Bystritsky, Alexander; Xia, Guohua; Tendler, Aron; Daskalakis, Zafiris J; Winston, Jaron L; Dannon, Pinhas; Hafez, Hisham M; Reti, Irving M; Morales, Oscar G; Schlaepfer, Thomas E; Hollander, Eric; Berman, Joshua A; Husain, Mustafa M; Sofer, Uzi; Stein, Ahava; Adler, Shmulik; Deutsch, Lisa; Deutsch, Frederic; Roth, Yiftach; George, Mark S; Zangen, Abraham

    2015-01-01

    Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p+0.013; remission: 32.6 vs. 14.6%, p+0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment. PMID:25655160

  1. Late outcomes after acute pulmonary embolism: rationale and design of FOCUS, a prospective observational multicenter cohort study.

    PubMed

    Konstantinides, Stavros V; Barco, Stefano; Rosenkranz, Stephan; Lankeit, Mareike; Held, Matthias; Gerhardt, Felix; Bruch, Leonard; Ewert, Ralf; Faehling, Martin; Freise, Julia; Ghofrani, Hossein-Ardeschir; Grünig, Ekkehard; Halank, Michael; Heydenreich, Nadine; Hoeper, Marius M; Leuchte, Hanno H; Mayer, Eckhard; Meyer, F Joachim; Neurohr, Claus; Opitz, Christian; Pinto, Antonio; Seyfarth, Hans-Jürgen; Wachter, Rolf; Zäpf, Bianca; Wilkens, Heinrike; Binder, Harald; Wild, Philipp S

    2016-11-01

    Acute pulmonary embolism (PE) is a frequent cause of death and serious disability. The risk of PE-associated mortality and morbidity extends far beyond the acute phase of the disease. In earlier follow-up studies, as many as 30 % of the patients died during a follow-up period of up to 3 years, and up to 50 % of patients continued to complain of dyspnea and/or poor physical performance 6 months to 3 years after the index event. The most feared 'late sequela' of PE is chronic thromboembolic pulmonary hypertension (CTEPH), the true incidence of which remains obscure due to the large margin of error in the rates reported by mostly small, single-center studies. Moreover, the functional and hemodynamic changes corresponding to early, possibly reversible stages of CTEPH, have not been systematically investigated. The ongoing Follow-Up after acute pulmonary embolism (FOCUS) study will prospectively enroll and systematically follow, over a 2-year period and with a standardized comprehensive program of clinical, echocardiographic, functional and laboratory testing, a large multicenter prospective cohort of 1000 unselected patients (all-comers) with acute symptomatic PE. FOCUS will possess adequate power to provide answers to relevant remaining questions regarding the patients' long-term morbidity and mortality, and the temporal pattern of post-PE abnormalities. It will hopefully provide evidence for future guideline recommendations regarding the selection of patients for long-term follow-up after PE, the modalities which this follow-up should include, and the findings that should be interpreted as indicating progressive functional and hemodynamic post-PE impairment, or the development of CTEPH.

  2. QIN DAWG Validation of Gradient Nonlinearity Bias Correction Workflow for Quantitative Diffusion-Weighted Imaging in Multicenter Trials

    PubMed Central

    Malyarenko, Dariya I.; Wilmes, Lisa J.; Arlinghaus, Lori R.; Jacobs, Michael A.; Huang, Wei; Helmer, Karl G.; Taouli, Bachir; Yankeelov, Thomas E.; Newitt, David; Chenevert, Thomas L.

    2017-01-01

    Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, −35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI. PMID:28105469

  3. A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis‐Related Arthritis

    PubMed Central

    Tse, Shirley M. L.; Horneff, Gerd; Pangan, Aileen L.; Kalabic, Jasmina; Goss, Sandra; Unnebrink, Kristina; Anderson, Jaclyn K.

    2015-01-01

    Objective Enthesitis‐related arthritis (ERA) is a juvenile idiopathic arthritis (JIA) category, primarily affecting entheses and peripheral joints. This study evaluated efficacy, safety, and pharmacokinetics of adalimumab versus placebo in patients with ERA. Methods This is a phase III, multicenter, randomized double‐blind study in patients ages ≥6 to <18 years with ERA treated with adalimumab (24 mg/m2, maximum dose 40 mg every other week) or placebo for 12 weeks, followed by up to 192 weeks of open‐label adalimumab. The primary end point was percent change from baseline in number of active joints with arthritis (AJC) at week 12. Samples were collected to determine adalimumab serum concentrations. Adverse events (AEs) were assessed throughout the study. Results Forty‐six patients were randomized (31 adalimumab/15 placebo). At baseline, mean age was 12.9 years, mean duration of ERA symptoms was 2.6 years, mean AJC was 7.8, and mean enthesitis count was 8.1. Mean percent change from baseline in AJC at week 12 was greater in the adalimumab group versus placebo (−62.6% versus −11.6%; P = 0.039). Most secondary variables favored adalimumab versus placebo at week 12. Treatment response further increased with continued adalimumab therapy through week 52. Mean steady‐state adalimumab serum concentrations were 7.5–11.8 μg/ml, similar to patients age ≥2 years with polyarticular JIA. AE rates were similar between placebo and adalimumab: any AE (53.3% versus 67.7%), serious AEs (0% versus 3.2%), and infectious AEs (20.0% versus 29.0%). Conclusion Adalimumab reduced signs and symptoms of ERA at week 12, with improvement sustained through week 52. The safety profile was consistent with previous adalimumab studies. PMID:26223543

  4. Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial

    PubMed Central

    Hyun, Jong Jin; Lee, Hong Sik; Kim, Chang Duck; Dong, Seok Ho; Lee, Seung-Ok; Ryu, Ji Kon; Lee, Don Haeng; Jeong, Seok; Kim, Tae Nyeun; Lee, Jin; Koh, Dong Hee; Park, Eun Taek; Lee, Inseok; Yoo, Byung Moo; Kim, Jin Hong

    2015-01-01

    Background/Aims Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. Methods A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. Results A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Conclusions Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies. PMID:26087862

  5. Oral mifepristone 600 mg and vaginal gemeprost for mid-trimester induction of abortion. An open multicenter study. UK Multicenter Study Group.

    PubMed

    1997-12-01

    This open multicenter study was performed in 20 hospital gynecological units in the UK. The effects of 600 mg oral mifepristone as pretreatment to vaginal prostaglandin induction of second trimester abortion was studied in 267 women. The primary efficacy variable was the abortion induction interval, defined as the time taken to expel the fetus from the time of administration of the first prostaglandin pessary. Induction was commenced 36 to 48 hours following mifepristone intake. The mean abortion induction interval was 7 h. A total of 81.9% of women aborted within 12 h. There was a significant relationship between abortion induction interval and age of gestation, and a significant inverse relationship between abortion induction interval and parity. Vomiting, pelvic pain, and nausea were the most frequently reported adverse events. Two patients required transfusion and one patient with a uterine scar from a previous cesarean section suffered a ruptured uterus and hysterotomy.

  6. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    SciTech Connect

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  7. Extremal multicenter black holes: nilpotent orbits and Tits Satake universality classes

    NASA Astrophysics Data System (ADS)

    Fré, Pietro; Sorin, Alexander S.

    2013-01-01

    Four dimensional supergravity theories whose scalar manifold is a symmetric coset manifold UD=4/Hc are arranged into a finite list of Tits Satake universality classes. Stationary solutions of these theories, spherically symmetric or not, are identified with those of an euclidian three-dimensional σ-model, whose target manifold is a Lorentzian coset UD=3/H* and the extremal ones are associated with H* nilpotent orbits in the K* representation emerging from the orthogonal decomposition of the algebra {U} D=3 with respect to H*. It is shown that the classification of such orbits can always be reduced to the Tits-Satake projection and it is a class property of the Tits Satake universality classes. The construction procedure of Bossard et al of extremal multicenter solutions by means of a triangular hierarchy of integrable equations is completed and converted into a closed algorithm by means of a general formula that provides the transition from the symmetric to the solvable gauge. The question of the relation between H* orbits and charge orbits W of the corresponding black holes is addressed and also reduced to the corresponding question within the Tits Satake projection. It is conjectured that on the vanishing locus of the Taub-NUT current the relation between H*-orbit and W-orbit is rigid and one-to-one. All black holes emerging from multicenter solutions associated with a given H* orbit have the same W-type. For the S 3 model we provide a complete survey of its multicenter solutions associated with all of the previously classified nilpotent orbits of {s}{l}(2)× {s}{l}(2) within {{{g}}_{2,2 }} . We find a new intrinsic classification of the W-orbits of this model that might provide a paradigm for the analogous classification in all the other Tits Satake universality classes.

  8. Suicide prevention by lithium SUPLI--challenges of a multi-center prospective study.

    PubMed

    Lauterbach, Erik; Ahrens, Bernd; Felber, Werner; Oerlinghausen, Bruno Muller; Kilb, Birgit; Bischof, Gerd; Heuser, Isabella; Werner, Petra; Hawellek, Barbara; Maier, Wolfgang; Lewitzka, Ute; Pogarell, Oliver; Hegerl, Ulrich; Bronisch, Thomas; Richter, Kneginja; Niklewski, Günther; Broocks, Andreas; Hohagen, Fritz

    2005-01-01

    Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented.

  9. Design and methods in a multi-center case-control interview study.

    PubMed Central

    Hartge, P; Cahill, J I; West, D; Hauck, M; Austin, D; Silverman, D; Hoover, R

    1984-01-01

    We conducted a case-control study in ten areas of the United States in which a total of 2,982 bladder cancer patients and 5,782 population controls were interviewed. We employed a variety of existing and new techniques to reduce bias and to monitor the quality of data collected. We review here many of the design elements and field methods that can be generally applied in epidemiologic studies, particularly multi-center interview studies, and explain the reasons for our selection of the methods, instruments, and procedures used. PMID:6689843

  10. Open, multicenter study to evaluate the tolerability and efficacy of Echinaforce Forte tablets in athletes.

    PubMed

    Schoop, Ronald; Büechi, Samuel; Suter, Andy

    2006-01-01

    This open, multicenter study investigated the tolerability and efficacy of a new tablet formulation of Echinacea purpurea extract (Echinaforce Forte; A. Vogel, Bioforce AG, Roggwil, Switzerland) in 80 subjects actively involved in sports. Most investigators (97.5%) rated the treatment as having "very good" or "good" tolerability. About 75% of patients and investigators rated its efficacy during a common cold as "very good" or "good," and 71% of subjects were free of cold episodes. This study is the first to suggest that Echinaforce is effective in the prophylaxis, as well as the treatment, of the common cold in persons who actively participate in sports.

  11. Multicenter molecular integrals for Slater orbitals of higher principal quantum numbers

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    As was shown earlier by Tai (1979), by using the Fourier-transform technique and properly coupling a pair of two-center exchange integrals, the multicenter molecular integrals can be cast into a simple expression upon which numerical procedures can be directly applied. In this paper, the procedure of Tai is extended to integrals involving orbitals with arbitrarily higher principal quantum number. The derivation is outlined, and the explicit expressions are presented for a three-center nuclear attraction integral and a four-center two-electron Coulomb repulsion integral of arbitrary higher states.

  12. Calculation of multicenter electric field gradient integrals over Slater-type orbitals using unsymmetrical one-range addition theorems.

    PubMed

    Guseinov, Israfil I; Görgün, Nurşen Seçkin

    2011-06-01

    The electric field induced within a molecule by its electrons determines a whole series of important physical properties of the molecule. In particular, the values of the gradient of this field at the nuclei determine the interaction of their quadrupole moments with the electrons. Using unsymmetrical one-range addition theorems introduced by one of the authors, the sets of series expansion relations for multicenter electric field gradient integrals over Slater-type orbitals in terms of multicenter charge density expansion coefficients and two-center basic integrals are presented. The convergence of the series is tested by calculating concrete cases for different values of quantum numbers, parameters and locations of orbitals.

  13. Variation among institutional review boards in evaluating the design of a multicenter randomized trial

    PubMed Central

    Stark, AR; Tyson, JE; Hibberd, PL

    2010-01-01

    Objective The objective of the study was to examine the variation among institutional review boards (IRBs) in evaluation of the study design of a multicenter trial. Study Design We assessed the first written response of local IRBs to each site investigator for a multicenter trial of vitamin A supplementation in extremely low birth weight (ELBW) infants performed by the National Institute of Child Health and Human Development Neonatal Research Network. Each author of this paper independently reviewed and categorized IRB concerns as major, minor or none, according to the predefined criteria. Result Initially, 9 of 18 IRBs withheld approval because of at least one major concern. These concerns reflected difficulties in evaluating specific scientific issues for the design of the trial, including its justification, enrollment criteria, control and experimental therapies, co-interventions, toxicity assessment, outcome monitoring and informed consent. Conclusion The difficulty in assessing appropriate trial design for the specific hypothesis under investigation resulted in considerable variability in the evaluation by local IRBs. PMID:19798046

  14. A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Gerdtsson, Anna S.; Malats, Núria; Säll, Anna; Real, Francisco X.; Porta, Miquel; Skoog, Petter; Persson, Helena; Wingren, Christer; Borrebaeck, Carl A. K.

    2015-01-01

    Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91–100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis. PMID:26587286

  15. Multicenter Quality Control of Hepatitis C Virus Protease Inhibitor Resistance Genotyping

    PubMed Central

    Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-01-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents. PMID:23426922

  16. Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping.

    PubMed

    Vallet, Sophie; Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-05-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

  17. Quantitative analysis of tomographic stress thallium-201 myocardial scintigrams: a multicenter trial.

    PubMed

    Van Train, K F; Maddahi, J; Berman, D S; Kiat, H; Areeda, J; Prigent, F; Friedman, J

    1990-07-01

    The accuracy of the previously developed and validated Cedars-Sinai Medical Center (CSMC) computer program for quantitative analysis of thallium-201 (201TI) stress myocardial tomograms was assessed in a multicenter trial consisting of 242 patients with coronary angiography and 76 with a low likelihood (LL) of coronary artery disease (CAD) involving various cameras, computers, and operators. The program utilized gender-matched normal limits developed from 35 LL patients at CSMC. The multicenter results as compared to those of 168 patients from CSMC were not significantly different with respect to the overall sensitivities (94% versus 95%) and specificities (44% versus 56%) for identification of CAD and normalcy rates which were determined in LL patients (82% for both) and with respect to identification of individual diseased arteries. The results indicate that our method for quantifying tomographic 201TI stress scintigrams utilizing standard normal limits can be applied at other institutions by different operators, using a variety of cameras and computers, with similar accuracy to that currently obtained at our institution.

  18. A Prospective Multi-Center Audit of Nutrition Support Parameters Following Burn Injury.

    PubMed

    Kurmis, Rochelle; Heath, Kathryn; Ooi, Selena; Munn, Zachary; Forbes, Sharon; Young, Vicki; Rigby, Paul; Wood, Kate; Phillips, Frances; Greenwood, John

    2015-01-01

    The importance of nutrition support delivery to the severe burn-injured patient is well recognized, however, nutrition provision to the patient may be sub optimal in practice. The aim of this study was to conduct a prospective multi-center audit across Australia and New Zealand using the Joanna Briggs Institute Burns Node Nutrition audit criteria. Thirty-four patients with severe burn injury (≥20% TBSA in adults and ≥10% TBSA in children) were identified on admission or on referral to the Dietitian at the eight participating Burn Units between February 1, 2012 and April 30, 2012 for inclusion in the study. De-identified patient data was analyzed using the Joanna Briggs Institute, Practical Application of Clinical Evidence System. Compliance with individual audit criterion ranged from 33 to 100%. Provision of prescribed enteral feed volumes and weekly weighing of patients were highlighted as key areas for clinical improvement. Clinical audit is a valuable tool for evaluating current practice against best evidence to ensure that quality patient care is delivered. The use of the Joanna Briggs Institute Burns Node audit criteria has allowed for a standardized multi-center audit to be conducted. Improving nutrition support delivery in burn patients was identified as a key area requiring ongoing clinical improvement across Australia and New Zealand. Clinician feedback on use of the audit criteria will allow for future refinement of individual criterion, and presentation of results of this audit has resulted in a review of the Bi-National Burns Registry nutrition quality indicators.

  19. Multi-center harmonization of flow cytometers in the context of the European "PRECISESADS" project.

    PubMed

    Jamin, Christophe; Le Lann, Lucas; Alvarez-Errico, Damiana; Barbarroja, Nuria; Cantaert, Tineke; Ducreux, Julie; Dufour, Aleksandra Maria; Gerl, Velia; Kniesch, Katja; Neves, Esmeralda; Trombetta, Elena; Alarcón-Riquelme, Marta; Marañon, Concepción; Pers, Jacques-Olivier

    2016-11-01

    The innovative medicine initiative project called PRECISESADS will study 2.500 individuals affected by systemic autoimmune diseases (SADs) and controls. Among extensive OMICS approaches, multi-parameter flow cytometry analyses will be performed in eleven different centers. Therefore, the integration of all data in common bioinformatical and biostatistical investigations requires a fine mirroring of all instruments. We describe here the procedure elaborated to achieve this prerequisite. One flow cytometer chosen as reference instrument fixed the mean fluorescence intensities (MFIs) of 8 different fluorochrome-conjugated antibodies (Abs) using VersaComp Ab capture beads. The ten other centers adjusted their own PMT voltages to reach the same MFIs. Subsequently, all centers acquired Rainbow 8-peak beads data on a daily basis to follow the stability of their instrument overtime. One blood sample has been dispatched and concomitantly stained in all centers. Comparison of leukocytes frequencies and cell surface marker MFIs demonstrated the close sensitivity of all flow cytometers, allowing a multicenter analysis. The effective multi-center harmonization enables the constitution of a workable wide flow cytometry database for the identification of specific molecular signatures in individuals with SADs.

  20. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

    PubMed

    Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

    2015-02-01

    The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

  1. Multicenter evaluation of single-photon emission computed tomography quantification with third-party reconstruction software.

    PubMed

    Kangasmaa, Tuija S; Constable, Chris; Hippeläinen, Eero; Sohlberg, Antti O

    2016-09-01

    Reliable and reproducible quantification is essential in many clinical situations. Previously, single-photon emission computed tomography (SPECT) has not been considered a quantitative imaging modality, but recent advances in reconstruction algorithm development have made SPECT quantitative. In this study, we investigate the reproducibility of SPECT quantification with phantoms in a multicenter setting using novel third-party reconstruction software. A total of five hospitals and eight scanners (three GE scanners and five Siemens scanners) participated in the study. A Jaszczak phantom without inserts was used to calculate counts to activity concentration conversion factors. The quantitative accuracy was tested using the NEMA-IEC phantom with six spherical inserts (diameters from 10 to 37 mm) filled to an 8 : 1 insert-background concentration ratio. Phantom studies were reconstructed at one central location using HERMES HybridRecon applying corrections for attenuation, collimator-detector response, and scatter. Spherical volumes of interest with the same diameter as the inserts were drawn on the images and recovery coefficients for the spheres were calculated. The coefficient of variation (CoV) of the NEMA-IEC phantom recovery coefficients ranged from ∼19 to 5% depending on the insert diameter so that the lowest CoV was obtained with the largest spheres. The intersite CoV was almost equal to intrasite CoV. In conclusion, quantitative SPECT is reproducible in a multicenter setting with third-party reconstruction software.

  2. A Multi-Center Controlled Study of the Acute and Chronic Effects of Cooling Therapy for MS

    NASA Technical Reports Server (NTRS)

    Luna, Bernadette; Schwid, Steven W.; Cutter, Gary; Murray, Ronald; Bowen, James; Pellegrino, Richard; Guisado, Raul; Webbon, Bruce W.; DeVincenzi, Donald (Technical Monitor)

    2000-01-01

    To determine the acute and chronic effects of cooling therapy on patients with MS using objective functional performance measures and self-assessed measures of fatigue. Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. Significant acute and chronic effects of cooling have not been demonstrated in a multi-center, controlled, blinded study using objective measures of neurologic function. Patients (N=84) with definite MS, mild to moderate disability (EDSS less than 6.0), and self-reported heat sensitivity were enrolled at 5 study sites. Acute effects of cooling were assessed by randomly assigning subjects to high-dose or low-dose cooling for one hour using an active cooling vest and cap (Life Enhancement Technologies, Santa Clara, CA). Settings were individualized to maintain the cooling garments at 55 F for the high-dose treatment and 70 F for the low-dose treatment. Both patients and examining investigators were blinded to treatment assignments. The MSFC and visual acuity/contrast sensitivity were assessed before and 30 minutes after treatment. The following week, subjects had an identical visit with the alternate cooling treatment. Chronic effects of cooling were assessed by randomly assigning the same subjects to unblinded daily home cooling or observation for 4 weeks. All subjects completed the Rochester Fatigue Diary (RFD) twice weekly and subjective measures of strength, cognition, and energy level daily. At the end of the period, subjects completed the Modified Fatigue Impact Scale (MFIS) and underwent another high-dose cooling session with assessment of the MSFC and vision. After a one-week washout period, subjects crossed over to the alternate 4-week treatment. Oral temperatures were reduced with both acute treatments (0.8 +/- .06 F, high and 0.5 +/- .06 F, low). While mean MSFC did not change significantly during individual cooling sessions, post hoc analysis pooling the 3 high-dose cooling sessions revealed an

  3. Factors Influencing Medical Student Attrition and Their Implications in a Large Multi-Center Randomized Education Trial

    ERIC Educational Resources Information Center

    Kalet, A.; Ellaway, R. H.; Song, H. S.; Nick, M.; Sarpel, U.; Hopkins, M. A.; Hill, J.; Plass, J. L.; Pusic, M. V.

    2013-01-01

    Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the…

  4. Preliminary MRI quality assessment and device acceptance guidelines for a multicenter bioclinical study: the GO Glioblastoma Project.

    PubMed

    Ollivro, Sylvain; Eliat, Pierre-Antoine; Hitti, Eric; Tran, Loan; de Certaines, Jacques D; Saint-Jalmes, Hervé

    2012-10-01

    It is a major challenge to guarantee homogeneous acquisition during a prospective multicenter magnetic resonance imaging (MRI) study that makes use of different devices. The goal of the multicenter Grand Ouest Glioblastoma Project (GOGP) was to correlate MRI quantitative parameters with biological markers extracted from image-guided biopsies. Therefore, it was essential to ensure spatial coherence of the parameters as well as the signal intensity and homogeneity. The project included the same MRI protocol implemented on six devices from different manufacturers. The key point was the initial acceptance of the imaging devices and protocol sequences. For this purpose, and to allow comparison of quantitative patient data, we propose a specific method for quality assessment. A common quality control based on 10 parameters was established. Three pulse sequences of the clinical project protocol were applied using three test-objects. A fourth test-object was used to assess T1 accuracy. Although geometry-related parameters, signal-to-noise ratio, uniformity, and T1 measurements varied slightly depending on the different devices, they nevertheless remained within the recommendations and expectations of the multicenter project. This kind of quality control procedure should be undertaken as a prerequisite to any multicenter clinical project involving quantitative MRI and comparison of data acquisitions with quantitative biological image-guided biopsies.

  5. Alcohol Consumption among University Students in North Rhine-Westphalia, Germany--Results from a Multicenter Cross-Sectional Study

    ERIC Educational Resources Information Center

    Akmatov, Manas K.; Mikolajczyk, Rafael T.; Meier, Sabine; Kramer, Alexander

    2011-01-01

    Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information…

  6. A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability

    PubMed Central

    Pastores, Gregory M.; Rosenbloom, Barry; Weinreb, Neal; Goker-Alpan, Ozlem; Grabowski, Gregory; Cohn, Gabriel M.; Zahrieh, David

    2014-01-01

    Purpose: To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase. Methods: This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/kg (treatment naïve) or 15–60 U/kg (previously treated). Results: A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti–velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients. Conclusion: The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy. PMID:24263462

  7. FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

    PubMed

    Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

    2009-01-01

    This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

  8. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO).

    PubMed

    Ayala, Fabio; Lambert, Julien

    2015-01-01

    Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

  9. Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

    PubMed Central

    Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

    2014-01-01

    Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

  10. Decision making among HIV+ drug using men who have sex with men: a preliminary report from the Chicago Multicenter AIDS Cohort Study.

    PubMed

    Martin, Eileen M; DeHaan, Samantha; Vassileva, Jasmin; Gonzalez, Raul; Weller, Joshua; Bechara, Antoine

    2013-01-01

    HIV+ substance-dependent individuals (SDIs) make significantly poorer decisions than HIV- SDIs, but the neurocognitive mechanisms underlying this impairment have not been identified. We administered the Iowa Gambling Task (IGT), a measure of decision making under uncertain risk, and the Cups Task, a measure of decision making under specified risk, to a group of 56 HIV+ and 23 HIV- men who have sex with men (MSMs) with a history of substance dependence enrolled in the Multicenter AIDS Cohort Study. The IGT provides no explicit information regarding the contingencies for each possible choice, and the probability of each outcome remains ambiguous at least for the early trials; in contrast, the Cups Task provides explicit information about the probability of each outcome. The HIV+ group made significantly poorer decisions on the IGT than the HIV- group. Cups Task performance did not differ significantly between HIV- and HIV+ groups. Exploratory analyses of the IGT data suggested that HIV+ subjects tended to perform more poorly during the early learning phase when uncertainty about specific outcomes was greatest. Additionally, performance on the final two trial blocks was significantly correlated with Stroop Interference scores, suggesting that IGT performance is driven increasingly by executive control during the later portion of the task. Potential cognitive mechanisms to be explored in later studies are discussed, including impairment in implicit learning processing.

  11. Decision Making and Drug Abuse Among HIV+ Men Who Have Sex with Men: A Preliminary Report from the Chicago Multicenter AIDS Cohort Study

    PubMed Central

    Martin, Eileen M.; DeHaan, Samantha; Vassileva, Jasmin; Gonzalez, Raul; Weller, Joshua; Bechara, Antoine

    2013-01-01

    HIV+ substance dependent individuals (SDIs) make significantly poorer decisions compared with HIV− SDIs, but the neurocognitive mechanisms underlying this impairment have not been identified. We administered the Iowa Gambling Task, a measure of decision making under uncertain risk, and the Cups Task, a measure of decision making under specified risk, to a group of 56 HIV+ and 23 HIV− men who have sex with men (MSMs) with a history of substance dependence enrolled in the Multicenter AIDS Cohort Study. The IGT provides no explicit information regarding the contingencies for each possible choice, and the probability of each outcome remains ambiguous at least for the early trials; in contrast, the Cups Task provides explicit information about the probability of each outcome. The HIV+ group made significantly poorer decisions on the IGT compared with the HIV− group. Cups Task performance did not differ significantly between HIV− and HIV+ groups. Exploratory analyses of the IGT data suggested that HIV+ subjects tended to perform more poorly during the early learning phase when uncertainty about specific outcomes was greatest. Additionally, performance on the final two trial blocks was significantly correlated with Stroop Interference scores, suggesting IGT performance is driven increasingly by executive control during the later portion of the task. Potential cognitive mechanisms to be explored in later studies are discussed, including impairment in implicit learning processing PMID:23701366

  12. Treatment of Acute Coronary Syndrome by Telemedically Supported Paramedics Compared With Physician-Based Treatment: A Prospective, Interventional, Multicenter Trial

    PubMed Central

    Brokmann, Jörg C; Conrad, Clemens; Rossaint, Rolf; Bergrath, Sebastian; Beckers, Stefan K; Tamm, Miriam; Czaplik, Michael

    2016-01-01

    Background Prehospital treatment of acute coronary syndrome (ACS) in German emergency medical services (EMSs) is reserved for EMS physicians due to legal issues. Objective The objective of this prospective, interventional, multicenter trial was to evaluate the quality of telemedically-delegated therapy and the possible complications in patients with ACS. Methods After approval by the ethics committee and trial registration, a one-year study phase was started in August 2012 with 5 ambulances, telemedically equipped and staffed with paramedics, in 4 German EMS districts. The paramedics could contact an EMS-physician–staffed telemedicine center. After initiation of an audio connection, real-time data transmission was automatically established. If required, 12-lead electrocardiogram (ECG) and still pictures could be sent. Video was streamed from inside each ambulance. All drugs, including opioids, were delegated to the paramedics based on standardized, predefined algorithms. To compare telemedically-delegated medication and treatment in ACS cases with regular EMS missions, a matched pair analysis with historical controls was performed. Results Teleconsultation was performed on 150 patients having a cardiovascular emergency. In 39 cases, teleconsultation was started due to suspected ACS. No case had a medical complication. Correct handling of 12-lead ECG was performed equally between the groups (study group, n=38 vs control group, n=39, P>.99). There were no differences in correct handling of intravenous administration of acetylsalicylic acid, heparin, or morphine between both the groups (study group vs control group): acetylsalicylic acid, n=31 vs n=33, P=.73; unfractionated heparin, n=34 vs n=33, P>.99; morphine, n=29 vs n=27, P=.50. The correct handling of oxygen administration was significantly higher in the study group (n=29 vs n=18, P=.007). Conclusions Telemedical delegation of guideline conform medication and therapy by paramedics in patients with ACS and was

  13. Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP.

    PubMed

    Yee, Joann L; McChesney, Michael B; Christe, Kari L

    2015-10-01

    Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston-Zagreb strain virus that had been attenuated after 22 passages on human diploid cells.

  14. Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

    PubMed Central

    Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

    2015-01-01

    Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

  15. CROSSOVERS BETWEEN EPIGENESIS AND EPIGENETICS. A MULTICENTER APPROACH TO THE HISTORY OF EPIGENETICS (1901-1975).

    PubMed

    Costa, Rossella; Frezza, Giulia

    2014-01-01

    The origin of epigenetics has been traditionally traced back to Conrad Hal Waddington's foundational work in 1940s. The aim of the present paper is to reveal a hidden history of epigenetics, by means of a multicenter approach. Our analysis shows that genetics and embryology in early XX century--far from being non-communicating vessels--shared similar questions, as epitomized by Thomas Hunt Morgan's works. Such questions were rooted in the theory of epigenesis and set the scene for the development of epigenetics. Since the 1950s, the contribution of key scientists (Mary Lyon and Eduardo Scarano), as well as the discussions at the international conference of Gif-sur-Yvette (1957) paved the way for three fundamental shifts of focus: 1. From the whole embryo to the gene; 2. From the gene to the complex extranuclear processes of development; 3. From cytoplasmic inheritance to the epigenetics mechanisms.

  16. [Results of the multicenter prospective study of cerebrolysin safety and efficacy in acute stroke].

    PubMed

    Skwortsova, V I; Stakhovskaia, L V; Shamalov, N A; Kerbikov, O B

    2006-01-01

    The multicenter prospective study of cerebrolysin safety and efficacy included 277 patients with ischemic stroke aged 55-85 years, who received therapy within 12 h from the disease development. Cerebrolysin was used in dosage 10 ml daily along with concomitant standard basic treatment during 10 days after stroke onset in 138 patients. A control group comprised 139 patients who received basic treatment only. A quantitative analysis of the dynamics of neurological deficit revealed the accelerated improvement by NIHSS score, modified Rankin score and Barthel index in the cerebrolysin group on days 10 and 28 (p<0,05). The significant improvement of NIHSS score was observed on day 28 (p<0,05) in patients treated with cerebrolysin within the first 3h after stroke onset comparing to those treated within 6-12h. The trial demonstrated cerebrolysin safety and good tolerability in treatment of ischemic stroke in the carotid artery territory as well as its favorable clinical effect.

  17. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for verbal fluency tests.

    PubMed

    Peña-Casanova, Jordi; Quiñones-Ubeda, Sonia; Gramunt-Fombuena, Nina; Quintana-Aparicio, María; Aguilar, Miquel; Badenes, Dolors; Cerulla, Noemí; Molinuevo, José Luis; Ruiz, Eva; Robles, Alfredo; Barquero, Maria Sagrario; Antúnez, Carmen; Martínez-Parra, Carlos; Frank-García, Anna; Fernández, Manuel; Alfonso, Verónica; Sol, Josep M; Blesa, Rafael

    2009-06-01

    Lexical fluency tests are frequently used in clinical practice to assess language and executive function. As part of the Spanish multicenter normative studies (NEURONORMA project), we provide age- and education-adjusted norms for three semantic fluency tasks (animals, fruit and vegetables, and kitchen tools), three formal lexical tasks (words beginning with P, M, and R), and three excluded letter fluency tasks (excluded A, E, and S). The sample consists of 346 participants who are cognitively normal, community dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may also be of considerable use for comparisons with other international normative studies. Finally, these norms should help improve the interpretation of verbal fluency tasks and allow for greater diagnostic accuracy.

  18. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for Boston naming test and token test.

    PubMed

    Peña-Casanova, Jordi; Quiñones-Ubeda, Sonia; Gramunt-Fombuena, Nina; Aguilar, Miquel; Casas, Laura; Molinuevo, José Luis; Robles, Alfredo; Rodríguez, Dolores; Barquero, María Sagrario; Antúnez, Carmen; Martínez-Parra, Carlos; Frank-García, Anna; Fernández, Manuel; Molano, Ana; Alfonso, Verónica; Sol, Josep M; Blesa, Rafael

    2009-06-01

    As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the Boston naming test and Token test. The sample consists of 340 and 348 participants, respectively, who are cognitively normal, community-dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Age and education affected the score of the both tests, but sex was found to be unrelated to naming and verbal comprehension efficiency. Our norms should provide clinically useful data for evaluating elderly Spaniards. The normative data presented here were obtained from the same study sample as all the other NEURONORMA norms and the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.

  19. A Machine Learning Approach to Identifying the Thought Markers of Suicidal Subjects: A Prospective Multicenter Trial.

    PubMed

    Pestian, John P; Sorter, Michael; Connolly, Brian; Bretonnel Cohen, Kevin; McCullumsmith, Cheryl; Gee, Jeffry T; Morency, Louis-Philippe; Scherer, Stefan; Rohlfs, Lesley

    2017-02-01

    Death by suicide demonstrates profound personal suffering and societal failure. While basic sciences provide the opportunity to understand biological markers related to suicide, computer science provides opportunities to understand suicide thought markers. In this novel prospective, multimodal, multicenter, mixed demographic study, we used machine learning to measure and fuse two classes of suicidal thought markers: verbal and nonverbal. Machine learning algorithms were used with the subjects' words and vocal characteristics to classify 379 subjects recruited from two academic medical centers and a rural community hospital into one of three groups: suicidal, mentally ill but not suicidal, or controls. By combining linguistic and acoustic characteristics, subjects could be classified into one of the three groups with up to 85% accuracy. The results provide insight into how advanced technology can be used for suicide assessment and prevention.

  20. Tree-structured survival analysis of patients with Pseudomonas aeruginosa bacteremia: A multicenter observational cohort study.

    PubMed

    Yoon, Young Kyung; Kim, Hyun Ah; Ryu, Seong Yeol; Lee, Eun Jung; Lee, Mi Suk; Kim, Jieun; Park, Seong Yeon; Yang, Kyung Sook; Kim, Shin Woo

    2017-02-01

    This study aimed to construct a prediction algorithm, which is readily applicable in the clinical setting, to determine the mortality rate for patients with P. aeruginosa bacteremia. A multicenter observational cohort study was performed retrospectively in seven university-affiliated hospitals in Korea from March 2012 to February 2015. In total, 264 adult patients with monomicrobial P. aeruginosa bacteremia were included in the analyses. Among the predictors independently associated with 30-day mortality in the Cox regression model, Pitt bacteremia score >2 and high-risk source of bacteremia were identified as critical nodes in the tree-structured survival analysis. Particularly, the empirical combination therapy was not associated with any survival benefit in the Cox regression model compared to the empirical monotherapy. This study suggests that determining the infection source and evaluating the clinical severity are critical to predict the clinical outcome in patients with P. aeruginosa bacteremia.

  1. Multicenter double-blind comparison of nomifensine and imipramine for efficacy and safety in depressed outpatients.

    PubMed

    Bremner, J D; Abrahams, L M; Crupie, J E; McCawley, A; Proctor, R C; Sathananthan, G L

    1984-04-01

    Nomifensine, a tetrahydroisoquinoline antidepressant, was compared with imipramine in a 4-week multicenter double-blind study of depressed outpatients (100 on nomifensine, 56 on imipramine). Nomifensine was at least as effective as imipramine in reducing depressive symptoms at average doses of 150 mg/day. When significant differences did occur on Hamilton Depression Rating Scale scores, they favored nomifensine for improvement in cognitive symptoms and interest in work and activities. Early in treatment, nomifensine patients also showed a better relationship between clinical response and side effects. The proportions of patients experiencing at least one side effect or dropping out due to side effects were almost twice as high in the imipramine group. Dry mouth and sedating effects were 2-3 times more frequent among imipramine patients. Thus, nomifensine demonstrated clinical efficacy at least comparable with imipramine but with indications of a more favorable side effects profile.

  2. Point charge representation of multicenter multipole moments in calculation of electrostatic properties

    NASA Technical Reports Server (NTRS)

    Sokalski, W. A.; Shibata, M.; Ornstein, R. L.; Rein, R.

    1993-01-01

    Distributed Point Charge Models (PCM) for CO, (H2O)2, and HS-SH molecules have been computed from analytical expressions using multi-center multipole moments. The point charges (set of charges including both atomic and non-atomic positions) exactly reproduce both molecular and segmental multipole moments, thus constituting an accurate representation of the local anisotropy of electrostatic properties. In contrast to other known point charge models, PCM can be used to calculate not only intermolecular, but also intramolecular interactions. Comparison of these results with more accurate calculations demonstrated that PCM can correctly represent both weak and strong (intramolecular) interactions, thus indicating the merit of extending PCM to obtain improved potentials for molecular mechanics and molecular dynamics computational methods.

  3. Reliable surrogate outcome measures in multicenter clinical trials of Duchenne muscular dystrophy.

    PubMed

    Mayhew, Jill E; Florence, Julaine M; Mayhew, Thomas P; Henricson, Erik K; Leshner, Robert T; McCarter, Robert J; Escolar, Diana M

    2007-01-01

    We studied the reliability of a series of endpoints in an evaluation of subjects with Duchenne muscular dystrophy (DMD). The endpoints included quantitative muscle tests (QMTs), timed function tests, forced vital capacity (FVC), and manual muscle tests (MMT). Thirty-one ambulatory subjects with DMD (mean age 8.9 years; range 5-16 years) were evaluated at eight sites by 15 newly trained evaluators as a test of interrater reliability of outcome measures. Both total QMT score [intraclass correlation coefficient (ICC) 0.96] and individual QMT assessments (ICC 0.85-0.96) were highly reliable. Forced vital capacity and all timed function tests were also highly reliable (ICC 0.97-0.99). MMT was the least reliable assessment method (ICC 0.61). These data suggest that primary surrogate outcome measures in large multicenter clinical trials in DMD should use QMT, FVC, or time function tests to obtain maximum power and greatest sensitivity.

  4. Moon Phases

    ERIC Educational Resources Information Center

    Riddle, Bob

    2010-01-01

    When teaching Moon phases, the focus seems to be on the sequence of Moon phases and, in some grade levels, how Moon phases occur. Either focus can sometimes be a challenge, especially without the use of models and observations of the Moon. In this month's column, the author describes some of the lessons that he uses to teach the phases of the Moon…

  5. Multicenter Comparison of Machine Learning Methods and Conventional Regression for Predicting Clinical Deterioration on the Wards

    PubMed Central

    Churpek, Matthew M; Yuen, Trevor C; Winslow, Christopher; Meltzer, David O; Kattan, Michael W; Edelson, Dana P

    2016-01-01

    OBJECTIVE Machine learning methods are flexible prediction algorithms that may be more accurate than conventional regression. We compared the accuracy of different techniques for detecting clinical deterioration on the wards in a large, multicenter database. DESIGN Observational cohort study. SETTING Five hospitals, from November 2008 until January 2013. PATIENTS Hospitalized ward patients INTERVENTIONS None MEASUREMENTS AND MAIN RESULTS Demographic variables, laboratory values, and vital signs were utilized in a discrete-time survival analysis framework to predict the combined outcome of cardiac arrest, intensive care unit transfer, or death. Two logistic regression models (one using linear predictor terms and a second utilizing restricted cubic splines) were compared to several different machine learning methods. The models were derived in the first 60% of the data by date and then validated in the next 40%. For model derivation, each event time window was matched to a non-event window. All models were compared to each other and to the Modified Early Warning score (MEWS), a commonly cited early warning score, using the area under the receiver operating characteristic curve (AUC). A total of 269,999 patients were admitted, and 424 cardiac arrests, 13,188 intensive care unit transfers, and 2,840 deaths occurred in the study. In the validation dataset, the random forest model was the most accurate model (AUC 0.80 [95% CI 0.80–0.80]). The logistic regression model with spline predictors was more accurate than the model utilizing linear predictors (AUC 0.77 vs 0.74; p<0.01), and all models were more accurate than the MEWS (AUC 0.70 [95% CI 0.70–0.70]). CONCLUSIONS In this multicenter study, we found that several machine learning methods more accurately predicted clinical deterioration than logistic regression. Use of detection algorithms derived from these techniques may result in improved identification of critically ill patients on the wards. PMID:26771782

  6. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand

    PubMed Central

    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A.; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting. PMID:26629810

  7. Multicenter Evaluation of Geometric Accuracy of MRI Protocols Used in Experimental Stroke

    PubMed Central

    Milidonis, Xenios; Lennen, Ross J.; Jansen, Maurits A.; Mueller, Susanne; Boehm-Sturm, Philipp; Holmes, William M.; Sena, Emily S.; Macleod, Malcolm R.; Marshall, Ian

    2016-01-01

    It has recently been suggested that multicenter preclinical stroke studies should be carried out to improve translation from bench to bedside, but the accuracy of magnetic resonance imaging (MRI) scanners routinely used in experimental stroke has not yet been evaluated. We aimed to assess and compare geometric accuracy of preclinical scanners and examine the longitudinal stability of one scanner using a simple quality assurance (QA) protocol. Six 7 Tesla animal scanners across six different preclinical imaging centers throughout Europe were used to scan a small structural phantom and estimate linear scaling errors in all orthogonal directions and volumetric errors. Between-scanner imaging consisted of a standard sequence and each center’s preferred sequence for the assessment of infarct size in rat models of stroke. The standard sequence was also used to evaluate the drift in accuracy of the worst performing scanner over a period of six months following basic gradient calibration. Scaling and volumetric errors using the standard sequence were less variable than corresponding errors using different stroke sequences. The errors for one scanner, estimated using the standard sequence, were very high (above 4% scaling errors for each orthogonal direction, 18.73% volumetric error). Calibration of the gradient coils in this system reduced scaling errors to within ±1.0%; these remained stable during the subsequent 6-month assessment. In conclusion, despite decades of use in experimental studies, preclinical MRI still suffers from poor and variable geometric accuracy, influenced by the use of miscalibrated systems and various types of sequences for the same purpose. For effective pooling of data in multicenter studies, centers should adopt standardized procedures for system QA and in vivo imaging. PMID:27603704

  8. Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

    PubMed Central

    Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

    2015-01-01

    Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

  9. Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop.

    PubMed

    Cointe, S; Judicone, C; Robert, S; Mooberry, M J; Poncelet, P; Wauben, M; Nieuwland, R; Key, N S; Dignat-George, F; Lacroix, R

    2017-01-01

    Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardization. A new strategy to standardize MP counts by flow cytometry was evaluated in a multicenter study. No difference was found between instruments using forward or side scatter as the trigger parameter. This study demonstrated that beads can be used as a standardization tool for MPs. Click to hear the ISTH Academy's webinar on microvesicles SUMMARY: Background Microparticles (MPs) are extracellular vesicles resulting from the budding of cellular membranes that have a high potential as emergent biomarkers; however, their clinical relevance is hampered by methodological enumeration concerns and a lack of standardization. Flow cytometry (FCM) remains the most commonly used technique with the best capability to determine the cellular origin of single MPs. However, instruments behave variably depending on which scatter parameter (forward (FSC) or side scatter (SSC)) provides the best resolution to discriminate submicron particles. To overcome this problem, a new approach, based on two sets of selected beads adapted to FSC or SSC-optimized instruments, was recently proposed to reproducibly enumerate platelet-derived MP counts among instruments with different optical systems. Objective The objective was to evaluate this strategy in an international workshop that included 44 laboratories accounting for 52 cytometers of 14 types. Methods/Results Using resolution capability and background noise level as criteria to qualify the instruments, the standardization strategy proved to be compatible with 85% (44/52) of instruments. All instruments correctly ranked the platelet MP (PMP) levels of two platelet-free plasma samples. The inter-laboratory variability of PMP counts was 37% and 28% for each sample. No difference was found between instruments using forward or side-scattered light as the relative sizing parameter. Conclusions Despite remaining limitations, this study is the first to

  10. Results of a prospective multicenter trial evaluating the ePTFE peritoneal onlay laparoscopic inguinal hernioplasty.

    PubMed

    Toy, F K; Moskowitz, M; Smoot, R T; Pleatman, M; Bagdasarian, A; Polito, W; Carey, S D; Schatz, R; Janes, K; Zipser, M E

    1996-12-01

    A 2.8-year prospective multicenter trial was conducted to evaluate the ePTFE peritoneal onlay laparoscopic inguinal hernioplasty. A total of 441 inguinal hernias were repaired in 351 patients (326 male; 25 female). Two hundred twenty-six of the hernias were direct, 185 indirect, 4 femoral, 26 pantaloon, 90 bilateral, and 92 recurrent. Standardized data collection forms were used and submitted for centralized data analysis. For the hernioplasty, Cooper's ligament was exposed and an 8 cm x 12 cm x 1 mm GORE-TEX Soft Tissue Patch was stapled circumferentially to Cooper's ligament and the endoabdominal fascia. Patients were followed at 1 week, 6 months, 1 year, and then annually. Three-month intervals were used as needed. There was a mean follow-up of 447 days, with 21% of the total repairs followed for more than 2 years and 56% for more than a year. The overall follow-up rate was 95.5%. The operative and postoperative complication rates were 0.45% and 8%, respectively. There were 17 recurrent hernias (3.8%). The range of experience among the investigators was 13 to 168 hernioplasties. With the completion of 25 cases per investigator, the recurrence rate fell to 0.39%. Postoperative analgesia averaged a 24-hr supply of medication; 12.2% of patients required no analgesia. Convalescence averaged 5.4 days, and return to work averaged 7.7 days. This multicenter trial demonstrates that the ePTFE laparoscopic peritoneal onlay inguinal hernioplasty is a safe and dependable repair, especially after the initial learning curve is surmounted.

  11. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease.

    PubMed

    Martinez-Martin, Pablo; Reddy, Prashanth; Katzenschlager, Regina; Antonini, Angelo; Todorova, Antoniya; Odin, Per; Henriksen, Tove; Martin, Anne; Calandrella, Daniela; Rizos, Alexandra; Bryndum, Narissah; Glad, Arne; Dafsari, Haidar Salimi; Timmermann, Lars; Ebersbach, Georg; Kramberger, Milica G; Samuel, Michael; Wenzel, Karoline; Tomantschger, Volker; Storch, Alexander; Reichmann, Heinz; Pirtosek, Zvezdan; Trost, Maja; Svenningsson, Per; Palhagen, Sven; Volkmann, Jens; Chaudhuri, K Ray

    2015-04-01

    Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson's disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared 43 patients on Apo (48.8% males, age 62.3 ± 10.6 years; disease duration: 14 ± 4.4 years; median H & Y stage 3; interquartile range [IQR]: 3-4) and 44 on IJLI (56.8% males, age 62.7 ± 9.1 years; disease duration: 16.1 ± 6.7 years; median H & Y stage 4; IQR, 3-4). Cohen's effect sizes (≥0.8 considered as large) were "large" with both therapies with respect to total motor, nonmotor, and quality-of-life scores. The Non-Motor Symptoms Scale (NMSS) with Apo showed moderate improvement, whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the NMSS showed significantly higher improvement with IJLI. Seventy-five percent on IJLI improved in their quality-of-life and nonmotor symptoms (NMS), whereas in the Apo group, a similar proportion improved in quality of life, but 40% in NMS. Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on this open-label, nonrandomized, comparative study, we report that, in advanced Parkinson's patients, both IJLI and Apo infusion therapy appear to provide a robust improvement in motor symptoms, motor complications, quality-of-life, and some NMS. Controlled, randomized studies are required.

  12. Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

    PubMed

    Naslund, Thomas C; Becker, Stacey Y

    2003-01-01

    Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success.

  13. Multicenter Clinical Trial of the Nucleus® Hybrid™ S8 Cochlear Implant: Final Outcomes

    PubMed Central

    Gantz, Bruce J; Dunn, Camille; Oleson, Jacob; Hansen, Marlan; Parkinson, Aaron; Turner, Christopher

    2015-01-01

    Objective The concept expanding electrical speech processing to those with more residual acoustic hearing with a less invasive shorter cochlear implant has been ongoing since 1999. A multi-center study of the Nucleus Hybrid S8 CI took place between 2002–11. This report describes the final outcomes of this clinical trial. Study Design Multi-Center longitudinal single subject design Methods Eighty-seven subjects received a Nucleus® Hybrid™ S8 implant in their poorer ear. Speech perception in quiet (CNC words) and in noise (BKB-SIN) was collected pre- and post-operatively at 3, 6, and 12 months. Subjective questionnaire data using the APHAB was also collected. Results Some level of hearing preservation was accomplished in 98% subjects with 90% maintaining a functional low-frequency pure-tone average (LFPTA) at initial activation. By 12 months, 5 subjects had total hearing loss and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the Hybrid and Combined conditions. The majority of had improvements with BKB-SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the 4 subscales of the APHAB. Conclusion The concept of hybrid speech processing has significant advantages for subjects with residual low-frequency hearing. In this study, the Nucleus® Hybrid™ S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device. Level of evidence 2c PMID:26756395

  14. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: Results of a multicenter Phase III study

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Richetti, Antonella; Bignardi, Mario; Corvo, Renzo; Gabriele, Pietro; Sormani, Maria Pia; Antognoni, Paolo

    2005-03-01

    Purpose: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. Methods and materials: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a 'biphasic concomitant boost' schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. Results: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% {+-} 4% for CF and 78% {+-} 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% {+-} 5% for CF and 64% {+-} 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% {+-} 4% and 27% {+-} 6% for CF and AF, respectively (p = 0.10). Conclusion: Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.

  15. Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

    SciTech Connect

    Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seok Ah; Lee, Keun Seok; Yun, Tak; Jeong, Seung-Yong; Choi, Hyo Seong; Lim, Seok-Byung; Chang, Hee Jin; Jung, Kyung Hae

    2011-11-01

    Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m{sup 2} 1 week before radiotherapy, and then cetuximab 250 mg/m{sup 2}/week, irinotecan 40 mg/m{sup 2}/week for 5 consecutive weeks and capecitabine 1,650 mg/m{sup 2}/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

  16. ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    ClinicalTrials.gov

    2016-10-11

    Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

  17. Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial

    PubMed Central

    Ueda, T.; Morioka, H.; Nishida, Y.; Kakunaga, S.; Tsuchiya, H.; Matsumoto, Y.; Asami, Y.; Inoue, T.; Yoneda, T.

    2015-01-01

    Background Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB. Patients and methods Seventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria. Results The proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months. Conclusion The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB. PMID:26205395

  18. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  19. Irreversible Electroporation (IRE) Fails to Demonstrate Efficacy in a Prospective Multicenter Phase II Trial on Lung Malignancies: The ALICE Trial

    SciTech Connect

    Ricke, Jens Jürgens, Julian H. W.; Deschamps, Frederic; Tselikas, Lambros; Uhde, Katja; Kosiek, Ortrud; Baere, Thierry De

    2015-04-15

    PurposeTo assess safety and efficacy of irreversible electroporation (IRE) of lung malignancies.Materials and MethodsPatients with primary and secondary lung malignancies and preserved lung function were included in this prospective single arm trial. Primary and secondary endpoints were safety and efficacy. Recruitment goal was 36 subjects in 2 centers. Patients underwent IRE under general anesthesia with probe placement performed in Fluoroscopy-CT. The IRE system employed was NanoKnife{sup ®} (Angiodynamics). System settings for the ablation procedure followed the manufacturer’s recommendations. The Mann–Whitney U test was used to evaluate the correlation of nine technical parameters with local tumor control. Median follow up was 12 months.ResultsThe expected efficacy was not met at interim analysis and the trial was stopped prematurely after inclusion of 23 patients (13/10 between both centers). The dominant tumor entity was colorectal (n = 13). The median tumor diameter was 16 mm (8–27 mm). Pneumothoraces were observed in 11 of 23 patients with chest tubes required in 8 (35 %). Frequently observed alveolar hemorrhage never led to significant hemoptysis. 14/23 showed progressive disease (61 %). Stable disease was found in 1 (4 %), partial remission in 1 (4 %) and complete remission in 7 (30 %) patients. The relative increase of the current during ablation was significantly higher in the group treated successfully as compared to the group presenting local recurrence (p < 0.05). Needle tract seeding was found in three cases (13 %).ConclusionsIRE is not effective for the treatment of lung malignancies. We hypothesize that the energy deposition with current IRE probes is highly sensitive to air exposure.

  20. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

    PubMed Central

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zülke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, René; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, André; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Turrión, Victor Sánchez; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Fändrich, Fred; Becker, Thomas; Söderdahl, Gunnar; Chazouillères, Olivier; Mäkisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Jürgen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Königsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    2016-01-01

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. PMID:26555945

  1. Distribution of guidance models for cardiac resynchronization therapy in the setting of multi-center clinical trials

    NASA Astrophysics Data System (ADS)

    Rajchl, Martin; Abhari, Kamyar; Stirrat, John; Ukwatta, Eranga; Cantor, Diego; Li, Feng P.; Peters, Terry M.; White, James A.

    2014-03-01

    Multi-center trials provide the unique ability to investigate novel techniques across a range of geographical sites with sufficient statistical power, the inclusion of multiple operators determining feasibility under a wider array of clinical environments and work-flows. For this purpose, we introduce a new means of distributing pre-procedural cardiac models for image-guided interventions across a large scale multi-center trial. In this method, a single core facility is responsible for image processing, employing a novel web-based interface for model visualization and distribution. The requirements for such an interface, being WebGL-based, are minimal and well within the realms of accessibility for participating centers. We then demonstrate the accuracy of our approach using a single-center pacemaker lead implantation trial with generic planning models.

  2. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.

    PubMed

    Lindberg, Jill S; Culleton, Bruce; Wong, Gordon; Borah, Michael F; Clark, Roderick V; Shapiro, Warren B; Roger, Simon D; Husserl, Fred E; Klassen, Preston S; Guo, Matthew D; Albizem, Moetaz B; Coburn, Jack W

    2005-03-01

    Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of < or =250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels < or =300 pg/ml (46 versus 9%), proportion of patients with > or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

  3. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.

    PubMed

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-10-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] "top scoring pairs" polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3' untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible.

  4. Stable Atlas-based Mapped Prior (STAMP) Machine-learning Segmentation for Multicenter Large-scale MRI Data

    PubMed Central

    Kim, Eun Young; Magnotta, Vincent A.; Liu, Dawei; Johnson, Hans J.

    2014-01-01

    Machine learning (ML)-based segmentation methods are a common technique in the medical image processing field. In spite of numerous research groups that have investigated ML-based segmentation frameworks, there remains unanswered aspects of performance variability for the choice of two key components: ML-algorithm and intensity normalization. This investigation reveals that the choice of those elements plays a major part in determining segmentation accuracy and generalizability. The approach we have used in this study aims to evaluate relative benefits of the two elements within a subcortical MRI segmentation framework. Experiments were conducted to contrast eight machine-learning algorithm configurations and 11 normalization strategies for our brain MR segmentation framework. For the intensity normalization, a stable atlas-based mapped prior (STAMP) was utilized to take better account of contrast along boundaries of structures. Comparing eight machine learning algorithms on down-sampled segmentation MR data, it was obvious that a significant improvement was obtained using ensemble-based ML algorithms (i.e., random forest) or ANN algorithms. Further investigation between these two algorithms also revealed that the random forest results provided exceptionally good agreement with manual delineations by experts. Additional experiments showed that the effect of STAMP-based intensity normalization also improved the robustness of segmentation for multicenter data sets. The constructed framework obtained good multicenter reliability and was successfully applied on a large multicenter MR data set (n > 3000). Less than 10% of automated segmentations were recommended for minimal expert intervention. These results demonstrate the feasibility of using the ML-based segmentation tools for processing large amount of multicenter MR images. We demonstrated dramatically different result profiles in segmentation accuracy according to the choice of ML algorithm and intensity

  5. Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study

    PubMed Central

    Diener, Markus; Kropf, Siegfried; Otto, Ronny; Manger, Thomas; Vestweber, Boris; Mirow, Lutz; Winde, Günther; Lippert, Hans

    2016-01-01

    Background Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. Objective This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients’ perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. Methods The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. Results Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). Conclusions This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. Trial Registration German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http

  6. Stable Atlas-based Mapped Prior (STAMP) machine-learning segmentation for multicenter large-scale MRI data.

    PubMed

    Kim, Eun Young; Magnotta, Vincent A; Liu, Dawei; Johnson, Hans J

    2014-09-01

    Machine learning (ML)-based segmentation methods are a common technique in the medical image processing field. In spite of numerous research groups that have investigated ML-based segmentation frameworks, there remains unanswered aspects of performance variability for the choice of two key components: ML algorithm and intensity normalization. This investigation reveals that the choice of those elements plays a major part in determining segmentation accuracy and generalizability. The approach we have used in this study aims to evaluate relative benefits of the two elements within a subcortical MRI segmentation framework. Experiments were conducted to contrast eight machine-learning algorithm configurations and 11 normalization strategies for our brain MR segmentation framework. For the intensity normalization, a Stable Atlas-based Mapped Prior (STAMP) was utilized to take better account of contrast along boundaries of structures. Comparing eight machine learning algorithms on down-sampled segmentation MR data, it was obvious that a significant improvement was obtained using ensemble-based ML algorithms (i.e., random forest) or ANN algorithms. Further investigation between these two algorithms also revealed that the random forest results provided exceptionally good agreement with manual delineations by experts. Additional experiments showed that the effect of STAMP-based intensity normalization also improved the robustness of segmentation for multicenter data sets. The constructed framework obtained good multicenter reliability and was successfully applied on a large multicenter MR data set (n>3000). Less than 10% of automated segmentations were recommended for minimal expert intervention. These results demonstrate the feasibility of using the ML-based segmentation tools for processing large amount of multicenter MR images. We demonstrated dramatically different result profiles in segmentation accuracy according to the choice of ML algorithm and intensity

  7. Challenges in conducting multicenter, multicultural, and multilingual trials: a view from the literature and real-life experience reports.

    PubMed

    Hanson, Beate; De Faoite, Diarmuid

    2013-01-01

    A trend toward international multicenter clinical trials in the medical device industry is helping to increase recruitment figures and to improve the generalizability of results, among other factors. However, working globally creates its own unique set of problems, which are rarely discussed in the literature. This article considers these issues from multicenter, multicultural, and multilingual perspectives. A multicenter study implies a replication of work to coordinate research sites that are working under different regulations. Standardizing elements of the clinical trial is essential for proper comparison of results. Multicultural differences manifest themselves in different forms in international clinical research. However, the impact of culture on a study's success is a real issue, particularly when patient-reported outcomes form part of the trial. A trial that is conducted globally obviously requires the use of local language material, but this element is fraught with the possibility of mistranslation and misunderstanding. In this article, we also examine the composition of a research team and how to keep everyone involved in a global clinical trial both informed and enthused about a trial that may last several years. Examples from our own clinical investigations are reported throughout this article.

  8. Multicenter Comparison of Laboratory Performance in Cytomegalovirus and Epstein-Barr Virus Viral Load Testing using International Standards

    PubMed Central

    Rychert, Jenna; Danziger-Isakov, Lara; Yen-Lieberman, Belinda; Storch, Gregory; Buller, Richard; Sweet, Stewart C.; Mehta, Aneesh K.; Cheeseman, Jennifer A.; Heeger, Peter; Rosenberg, Eric S.; Fishman, Jay A.

    2015-01-01

    Background Infections with cytomegalovirus (CMV) and Epstein Barr Virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation (CTOT/CTOTC). Methods Viral load testing was performed on well-defined viral preparations according to standard operating procedures at each site. Results Among centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. EBV viral load data were more variable and less accurate despite the use of international standards. Conclusions These data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated by using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials. PMID:25303316

  9. Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

    PubMed Central

    Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

    2016-01-01

    Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

  10. Multicenter Case-Control Study on Restless Legs Syndrome in Multiple Sclerosis: the REMS Study

    PubMed Central

    Manconi, Mauro; Ferini-Strambi, Luigi; Filippi, Massimo; Bonanni, Enrica; Iudice, Alfonso; Murri, Luigi; Gigli, Gian Luigi; Fratticci, Lara; Merlino, Giovanni; Terzano, Giovanni; Granella, Franco; Parrino, Liborio; Silvestri, Rosalia; Aricò, Irene; Dattola, Vincenzo; Russo, Giovanna; Luongo, Carmela; Cicolin, Alessandro; Tribolo, Antonella; Cavalla, Paola; Savarese, Mariantonietta; Trojano, Maria; Ottaviano, Salvatore; Cirignotta, Fabio; Simioni, Valentina; Salvi, Fabrizio; Mondino, Fiorella; Perla, Franco; Chinaglia, Giorgia; Zuliani, Cristina; Cesnik, Edward; Granieri, Enrico; Placidi, Fabio; Palmieri, Maria Giuseppina; Manni, Raffaele; Terzaghi, Michele; Bergamaschi, Roberto; Rocchi, Raffaele; Ulivelli, Monica; Bartalini, Sabina; Ferri, Raffaele; Fermo, Salvatore Lo; Ubiali, Emilio; Viscardi, Massimo; Rottoli, Mariarosa; Nobili, Lino; Protti, Alessandra; Ferrillo, Franco; Allena, Marta; Mancardi, Gianluigi; Guarnieri, Biancamaria; Londrillo, Francesco

    2008-01-01

    Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56–8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs. Citation: Manconi M; Ferini-Strambi L; Filippi M; Bonanni E; Iudice A; Murri L; Gigli GL; Fratticci L; Merlino G; Terzano G; Granella F; Parrino L; Silvestri R; Aricò I; Dattola V; Russo G; Luongo

  11. PHASE DETECTOR

    DOEpatents

    Kippenhan, D.O.

    1959-09-01

    A phase detector circuit is described for use at very high frequencies of the order of 50 megacycles. The detector circuit includes a pair of rectifiers inverted relative to each other. One voltage to be compared is applied to the two rectifiers in phase opposition and the other voltage to be compared is commonly applied to the two rectifiers. The two result:ng d-c voltages derived from the rectifiers are combined in phase opposition to produce a single d-c voltage having amplitude and polarity characteristics dependent upon the phase relation between the signals to be compared. Principal novelty resides in the employment of a half-wave transmission line to derive the phase opposing signals from the first voltage to be compared for application to the two rectifiers in place of the transformer commonly utilized for such purpose in phase detector circuits for operation at lower frequency.

  12. [Multicenter Clinical Study of Vibrant Soundbridge in Japan: Analysis of Subjective Questionnaires].

    PubMed

    Kumakawa, Kozo; Kanzaki, Sho; Usami, Shin-ichi; Iwasaki, Satoshi; Yamanaka, Noboru; Doi, Katsumi; Naito, Yasushi; Gyo, Kiyofumi; Tono, Tetsuya; Takahashi, Haruo; Kanda, Yukihiko

    2015-11-01

    The Vibrant Soundbridge (VSB) is an active middle ear implant with the Floating Mass Transducer (FMT). We performed a multicenter study to study the efficacy of the VSB by means of "the 10 Questionnaire on Hearing 2002" and "the APHAB questionnaire" at 13 hospitals between 2011 and 2013. In all, 23 patients with mixed or conductive hearing loss received VSB implantation by the round window placement technique. These individuals were generally unable to use, or gained little from conventional hearing aids or bone conduction hearing aids. Two questionnaires were administrated before the surgery and 20 weeks after the VSB implantation. Scores on every item of "the 10 Questionnaire on Hearing 2002" showed significant improvement under noise after VSB implantation. On the APHAB, the scores for Ease of Communication, Reverberation, and Background subscales improved significantly after the VSB implantation, while the score for the Aversiveness subscale alone failed to show a positive improvement from the inexperience to the new sound. Analysis of the responses to these subjective questionnaires revealed better results after VSB implantation as compared to the preoperative data. In conclusion, RW vibroplasty with the use of VSB provided subjective benefit in patients with conductive and mixed hearing loss.

  13. Comprehensive rehabilitation with integrative medicine for subacute stroke: A multicenter randomized controlled trial

    PubMed Central

    Fang, Jianqiao; Chen, Lifang; Ma, Ruijie; Keeler, Crystal Lynn; Shen, Laihua; Bao, Yehua; Xu, Shouyu

    2016-01-01

    To determine whether integrative medicine rehabilitation (IMR) that combines conventional rehabilitation (CR) with acupuncture and Chinese herbal medicine has better effects for subacute stroke than CR alone, we conducted a multicenter randomized controlled trial that involved three hospitals in China. Three hundred sixty patients with subacute stroke were randomized into IMR and CR groups. The primary outcome was the Modified Barthel Index (MBI). The secondary outcomes were the National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer Assessment (FMA), the mini-mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA), Hamilton’s Depression Scale (HAMD), and the Self-Rating Depression Scale (SDS). All variables were evaluated at week 0 (baseline), week 4 (half-way of intervention), week 8 (after treatment) and week 20 (follow-up). In comparison with the CR group, the IMR group had significantly better improvements (P < 0.01 or P < 0.05) in all the primary and secondary outcomes. There were also significantly better changes from baseline in theses outcomes in the IMR group than in the CR group (P < 0.01). A low incidence of adverse events with mild symptoms was observed in the IMR group. We conclude that conventional rehabilitation combined with integrative medicine is safe and more effective for subacute stroke rehabilitation. PMID:27174221

  14. Multicenter testing of a burn prevention teaching tool for Amish children.

    PubMed

    Rieman, Mary T; Kagan, Richard J

    2013-01-01

    Burn prevention is not taught in Amish schools despite significant cultural risks for burn injuries related to scalds, ignition of clothing, and ignition of highly flammable materials. A culturally appropriate and acceptable burn prevention teaching tool was previously developed and pilot-tested in one Amish school. The purpose of this study was to perform further evaluation of this burn prevention teaching tool for Amish children. Following institutional review board approval, private schools were recruited via invitation in Amish newsletters. A teaching tool, which includes a magnetic story board, burn safety curriculum, and test questions, was provided to each school. Teachers obtained parental permission and informed assent for the children to participate. Teaching was guided by the curriculum and involved arranging magnetic pieces to illustrate and tell stories about burn hazards. The children were challenged to rearrange the magnets for a safer situation. Pretests and posttests were used to capture baseline knowledge and measure improvement. Scores were expressed as a percentage of the 33 test items answered correctly. Teachers provided recommendations and a written evaluation of the tool's usefulness. The participants were 294 students from 15 private Amish schools across eight states. Test scores were significantly improved by the lessons, without regard to gender or grade groups. Teachers valued the tool and recommended no changes. This multicenter study demonstrated that a culturally appropriate burn prevention teaching tool was highly effective for improving burn prevention knowledge among Amish school children. These results support expansion of burn prevention education to other Amish communities.

  15. Alveolar Ridge Reconstruction with Titanium Meshes and Simultaneous Implant Placement: A Retrospective, Multicenter Clinical Study

    PubMed Central

    Paraud Freixas, Andres; Han, Chang-Hun; Bechara, Sohueil; Tawil, Isaac

    2016-01-01

    Objective. To evaluate horizontal bone gain and implant survival and complication rates in patients treated with titanium meshes placed simultaneously with dental implants and fixed over them. Methods. Twenty-five patients treated with 40 implants and simultaneous guided bone regeneration with titanium meshes (i–Gen®, MegaGen, Gyeongbuk, Republic of Korea) were selected for inclusion in the present retrospective multicenter study. Primary outcomes were horizontal bone gain and implant survival; secondary outcomes were biological and prosthetic complications. Results. After the removal of titanium meshes, the CBCT evaluation revealed a mean horizontal bone gain of 3.67 mm (±0.89). The most frequent complications were mild postoperative edema (12/25 patients: 48%) and discomfort after surgery (10/25 patients: 40%); these complications were resolved within one week. Titanium mesh exposure occurred in 6 patients (6/25 : 24%): one of these suffered partial loss of the graft and another experienced complete graft loss and implant failure. An implant survival rate of 97.5% (implant-based) and a peri-implant marginal bone loss of 0.43 mm (±0.15) were recorded after 1 year. Conclusions. The horizontal ridge reconstruction with titanium meshes placed simultaneously with dental implants achieved predictable satisfactory results. Prospective randomized controlled trials on a larger sample of patients are required to validate these positive outcomes. PMID:27999799

  16. A multicenter study of major depressive disorder among emergency department patients in Latin-American countries.

    PubMed

    Castilla-Puentes, Ruby C; Secin, Ricardo; Grau, Arturo; Galeno, Roxanna; Feijo de Mello, Marcelo; Pena, Nuri; Sanchez-Russi, Carlos A

    2008-01-01

    This multicenter study estimated the prevalence of major depressive disorder (MDD) among emergency department patients in Latin America. To identify patients with MDD, we used a combination of DSM IV- criteria interview and a questionnaire screen including the center for Epidemiological Studies Depression Scale. We analyzed data from consecutive adult patients from hospitals in Argentina, Brazil, Chile, Colombia, and Mexico and described the demographic and health status differences between MDD and non-MDD patients. Prevalence of MDD ranges from 23.0 to 35.0%. The estimates are based on a total of 1,835 patients aged 18 years and over, with response rates of 83.0%. Compared to non-MDD patients, MDD patients were more likely to be middle-aged, female, smokers, of lower socioeconomic status, and to report a diagnosis of asthma or arthritis/rheumatism. Multivariate analysis identified a lower level of education, smoking, and self-reported anxiety, chronic fatigue, and back problems to be independently associated with MDD. Our data suggest that the prevalence of MDD is elevated among emergency department patients in Latin American countries. The integration of depression screening into routine emergency care merits serious consideration, especially if such screening can be linked to psychiatric treatment.

  17. Factors influencing the quality of postoperative epidural analgesia: an observational multicenter study

    PubMed Central

    Wranicz, Piotr; Andersen, Hege; Nordbø, Arve; Kongsgaard, Ulf E

    2014-01-01

    Background Epidural analgesia (EDA) is used widely for postoperative pain treatment. However, studies have reported a failure rate of EDA of up to 30%. We aimed to evaluate the quality of postoperative EDA in patients undergoing a laparotomy in five Norwegian hospitals. Methods This was a multicenter observational study in patients undergoing a laparotomy with epidural-based postoperative analgesia. Data were registered at three time points. Technical aspects, infusion rates, pain intensity, assessment procedures, side effects, and satisfaction of patients and health personnel were recorded. The use of other pain medications and coanalgesics was registered. Results Three hundred and seventeen patients were included. Pain control at rest was satisfactory in 89% of patients at 24 hours and in 91% at 48 hours. Pain control when coughing was satisfactory in 62% at 24 hours and in 59% at 48 hours. The spread of hypoesthesia was consistent for each individual patient but varied between patients. The hypoesthetic area was not associated with pain intensity, and the precision of the EDA insertion point was not associated with the pain score. Few side effects were reported. EDA was regarded as effective and functioning well by 64% of health personnel. Conclusion EDA was an effective method for postoperative pain relief at rest but did not give sufficient pain relief during mobilization. The use of cold stimulation to assess the spread of EDA had limited value as a clinical indicator of the efficacy of postoperative pain control. Validated tools for the control of EDA quality are needed. PMID:25206312

  18. Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study.

    PubMed

    Ayzenberg, Ilya; Schöllhammer, Joanna; Hoepner, Robert; Hellwig, Kerstin; Ringelstein, Marius; Aktas, Orhan; Kümpfel, Tania; Krumbholz, Markus; Trebst, Corinna; Paul, Friedemann; Pache, Florence; Obermann, Mark; Zeltner, Lena; Schwab, Matthias; Berthele, Achim; Jarius, Sven; Kleiter, Ingo

    2016-03-01

    Glatiramer acetate (GA) is an approved therapy for relapsing-remitting multiple sclerosis, but its efficacy for the prevention of attacks in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. We did a multicenter retrospective analysis of GA-treated patients with NMOSD, identified through a national registry. Annualized relapse rate and expanded disability status scale (EDSS) were the main outcome measures. We identified 23 GA-treated patients (21 female, 16 aquaporin-4 antibody-positive). GA was given for <6 months in seven patients; reasons for stopping were relapses (n = 3), confirmation of NMOSD (n = 2) and side effects (n = 2). Of 16 patients treated ≥ 6 months with GA (15 female, 11 aquaporin-4 antibody-positive), 14 experienced at least one relapse. There was no reduction in the mean annualized relapse rate in the total group (1.9 ± 1.1 before vs. 1.8 ± 1.4 during GA therapy), as well as in those patients who were aquaporin-4 antibody-positive, or had a history of prior immunotherapy or not. The median EDSS increased (2.5 start vs. 3.5 finish of GA, P < 0.05). GA therapy was discontinued in 15/16 patients; reasons were therapeutic inefficacy in 13 and post-injection skin reactions in two patients. We conclude that GA is not beneficial for preventing attacks in most patients with NMOSD, particularly in aquaporin-4 antibody-positive cases.

  19. Acupuncture for Smoking Cessation in Hong Kong: A Prospective Multicenter Observational Study

    PubMed Central

    Wang, Ying-ying; Wu, Yuan; Zhang, Ou; Chen, Min; Huang, Ling-ling; He, Xiu-qing; Wu, Guan-yi

    2016-01-01

    This was a prospective multicenter observational study, aiming to explore the effects of acupuncture on smoking cessation in Hong Kong. From March of 2010 to August of 2015, a total of 5202 smokers were recruited based on inclusion criteria and treated with acupuncture for 8 weeks. As a result, 2940 subjects finished the study with a drop-out rate of 43.48%. The self-reported 7-day point abstinence rate was 34.00% in Week 8 and 18.40% in Week 52. The exhaled carbon monoxide level and the number of cigarettes smoked per day were reduced significantly after treatment. The time to relapse was calculated to be 38.71 days. In addition, “cigarettes smoked per day,” “Fagerstrom Test for Nicotine Dependence,” “total sessions of acupuncture,” “whether finished 8 acupuncture treatments in the first month,” and “total sessions of acupuncture” were believed to be essential factors for abstinence success. It was concluded that acupuncture was a safe method for smoking cessation and was effective in helping smokers to quit; therefore, acupuncture could be considered as one of the methods to help smokers quit. Further studies regarding the effect differences between acupuncture and medications were needed to clarify the overall benefits of acupuncture. PMID:28003848

  20. Multicenter study of long-term (two-year) efficacy of lanthanum carbonate.

    PubMed

    Ando, Ryoichi; Kimura, Hitoshi; Sato, Hidehiko; Iwamoto, Shunsuke; Yoshizaki, Yuki; Chida, Yoshiko; Ishida, Yuji; Takayama, Masanobu; Yamada, Kouei; Tachibana, Ken; Ohtsuka, Masakazu; Kikuchi, Kan; Inoue, Atsushi

    2013-04-01

    Long-term efficacy of lanthanum carbonate on hyperphosphatemia was examined in multicenter dialysis patients. Outcome and efficacy after 2 years was investigated in 101 patients who had undergone lanthanum carbonate administration. Thirty-three cases dropped out by the 2-year point; patients undergoing at least 2 years of administration totaled 68. Reasons for dropping out were as follows: improvement of hyperphosphatemia, nine cases; changing hospitals, seven cases; medical complications, five cases; digestive symptoms, four cases; poor compliance, four cases; parathyroidectomy, two cases; death, two cases. The mean dosage was increased from initial daily dosage of 744 mg to 1266 mg after 1 year, and to 1246 mg after 2 years. Serum phosphate concentration decreased significantly from the initial 6.15 mg to 5.57 mg/dL after 1 year, and to 5.45 mg/dL after 2 years. Although a lowering trend was observed in corrected calcium levels, the difference was not significant. Parathyroid hormone was unchanged. Achievement rate of Japanese Society for Dialysis Therapy (JSDT) management target values for both phosphorus and calcium improved from 32.7% to 50.0% after 1 year, and to 56.5% after 2 years. Lanthanum carbonate is useful as a therapeutic tool for hyperphosphatemia over long durations.

  1. Multicenter study on the long-term (3-year) efficacy of lanthanum carbonate in dialysis patients.

    PubMed

    Ando, Ryoichi; Yama, Satomi; Ohnishi, Tsuyoshi; Iwamoto, Shunsuke; Kimura, Hitoshi; Chida, Yoshiko; Ishida, Yuji; Yamada, Kouei; Inagaki, Yuichiro; Takayama, Masanobu; Tachibana, Ken; Kikuchi, Kan; Inoue, Atsushi; Ohtsuka, Masakazu

    2014-06-01

    We previously conducted a multicenter study enrolling 101 dialysis patients with hyperphosphatemia in which lanthanum carbonate (LC) was administered for 2 years. In this study, the administration has been continued for an additional year, and we have evaluated the long-term (a total of 3 years) effects of LC. The average serum phosphorus (P) level was 6.05 mg/dL at the start and decreased to 5.84 mg/dL after 3 years, but no significant differences were observed at both points. The average serum corrected calcium (Ca) level significantly reduced after 3 years (P < 0.001). As results of evaluating the achievement rates with the management target values of serum P, Ca and intact parathyroid hormone (PTH) stated in the Japanese guideline, the achievement rates increased after 3 years. From these results, LC is considered to be a useful P binder that can be used for long-term treatment of hyperphosphatemia, without causing a Ca load.

  2. Multi-Center Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke using Permeability Imaging Features

    PubMed Central

    Scalzo, Fabien; Alger, Jeffry R.; Hu, Xiao; Saver, Jeffrey L.; Dani, Krishna A.; Muir, Keith W.; Demchuk, Andrew M.; Coutts, Shelagh B.; Luby, Marie; Warach, Steven; Liebeskind, David S.

    2013-01-01

    Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a crossvalidation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. PMID:23587928

  3. Environmental risk factors in pediatric psoriasis: a multicenter case-control study.

    PubMed

    Ozden, Müge G; Tekin, Nilgün S; Gürer, Mehmet A; Akdemir, Devrim; Doğramacı, Ciğdem; Utaş, Serap; Akman, Ayşe; Evans, Sibel E; Bahadır, Sevgi; Oztürkcan, Serap; Ikizoğlu, Güliz; Sendur, Neslihan; Köse, Osman; Bek, Yüksel; Yaylı, Savaş; Cantürk, Tayyar; Turanl, Ahmet Y

    2011-01-01

    To analyze the effect of possible risk factors, including breastfeeding, on the development of childhood-onset psoriasis, a multicenter case-control study with prospective collection of data was performed. Using a standard questionnaire, personal and specific variables including family history of psoriasis, maternal and environmental tobacco smoke exposure, body mass index (BMI), exclusive and partial breastfeeding for at least 3 and 12 months, cow's milk intake before 1 year, birth delivery method, and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18. Overall, patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls. The odds ratios (OR) for smoking and stressful life events were 2.90 (95% confidence interval [CI]=2.27-3.78) and 2.94 (95% CI=2.28-3.79), respectively. In addition, children with psoriasis were more likely to have a higher BMI (>26) than controls (OR=2.52; 95% CI=1.42-4.49). High BMI, environmental tobacco smoke exposure at home, and stressful life events may influence the development of pediatric psoriasis.

  4. Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

    PubMed Central

    Sen, H. Nida; Drye, Lea T.; Goldstein, Debra A.; Larson, Theresa A.; Merrill, Pauline T.; Pavan, Peter R.; Sheppard, John D.; Burke, Alyce; Srivastava, Sunil K.; Jabs, Douglas A.

    2013-01-01

    Purpose To assess the prevalence of hypotony in patients with severe forms of uveitis. Methods The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. Results Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01). Conclusions Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment. PMID:22409563

  5. [Multicenter study on the monitoring of in vitro susceptibility to tigeeyeline in Santiago, Chile].

    PubMed

    García C, Patricia; Juliet L, Chrystal; Fernández V, Alejandra; San Martín S, Marcela; Cifuentes D, Marcela; Porte T, Lorena; Braun J, Stephanie; Castillo D, Loriana; Vechiola H, Maggie; Tapia P, Cecilia; Sakurada Z, Andrea; Chanqueo C, Leonardo; Lam E, Marusella; Espinoza P, Mónica; Curcio F, Daniel

    2009-06-01

    The objective of this multicenter study was to determine tigecycline susceptibility rates, measured by agar diffusion, in nine hospitals in Santiago and to compare these rates with other antimicrobials. Each center studied 20 strains per month. All intermediate and fully resistant strains as well as 10% of susceptibile strains were also studied by the broth microdilution method. Overall, 2301 strains were studied displaying the following susceptibility rates for tigecycline: 100% for Streptococcus sp, Enterococcus sp, and E. coli respectively, 99.8% for Staphylococcus sp, 93% for Klebsiella and 80% for Acinetobacter baumarmii. For Proteus, Providencia and Morganella the susceptibility rates were 4%. For cefotaxime-resistant Klebsiella and imipenem-resistant A. baumarmii susceptibility rates were 95% and 80% respectively. The agar diffusion and broth dilution method were 100% concordant for tigecycline susceptible strains but only 27% for resistant or intermediate strains represented mostly by Acinetobacter baumannii. The majority of these strains (57/59) proved to be susceptible after retesting. The great majority (96,6%) of strains tested from nine Chilean hospitals proved to be susceptible to tigecycline with exception for Proteus, Providencia and Morganella (66% resistance). Using the agar diffusion method for measuring tigecycline susceptibility to A. baumannii may be misleading.

  6. Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

    PubMed Central

    2013-01-01

    Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

  7. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

    PubMed Central

    2012-01-01

    Introduction CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis. PMID:22531499

  8. Comprehensive rehabilitation with integrative medicine for subacute stroke: A multicenter randomized controlled trial.

    PubMed

    Fang, Jianqiao; Chen, Lifang; Ma, Ruijie; Keeler, Crystal Lynn; Shen, Laihua; Bao, Yehua; Xu, Shouyu

    2016-05-13

    To determine whether integrative medicine rehabilitation (IMR) that combines conventional rehabilitation (CR) with acupuncture and Chinese herbal medicine has better effects for subacute stroke than CR alone, we conducted a multicenter randomized controlled trial that involved three hospitals in China. Three hundred sixty patients with subacute stroke were randomized into IMR and CR groups. The primary outcome was the Modified Barthel Index (MBI). The secondary outcomes were the National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer Assessment (FMA), the mini-mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA), Hamilton's Depression Scale (HAMD), and the Self-Rating Depression Scale (SDS). All variables were evaluated at week 0 (baseline), week 4 (half-way of intervention), week 8 (after treatment) and week 20 (follow-up). In comparison with the CR group, the IMR group had significantly better improvements (P < 0.01 or P < 0.05) in all the primary and secondary outcomes. There were also significantly better changes from baseline in theses outcomes in the IMR group than in the CR group (P < 0.01). A low incidence of adverse events with mild symptoms was observed in the IMR group. We conclude that conventional rehabilitation combined with integrative medicine is safe and more effective for subacute stroke rehabilitation.

  9. Reappraisal of known malaria resistance loci in a large multicenter study.

    PubMed

    2014-11-01

    Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

  10. The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

    PubMed Central

    White, Daniel K.; Neogi, Tuhina; Zhang, Yuqing; Felson, David; LaValley, Michael; Niu, Jingbo; Nevitt, Michael; Lewis, Cora E.; Torner, James; Douglas Gross, K.

    2012-01-01

    Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9 ± 3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain. PMID:22645666

  11. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases.

    PubMed

    Respondek, Gesine; Stamelou, Maria; Kurz, Carolin; Ferguson, Leslie W; Rajput, Alexander; Chiu, Wan Zheng; van Swieten, John C; Troakes, Claire; Al Sarraj, Safa; Gelpi, Ellen; Gaig, Carles; Tolosa, Eduardo; Oertel, Wolfgang H; Giese, Armin; Roeber, Sigrun; Arzberger, Thomas; Wagenpfeil, Stefan; Höglinger, Günter U

    2014-12-01

    The phenotypic variability of progressive supranuclear palsy (PSP) may account for its frequent misdiagnosis, in particular in early stages of the disease. However, large multicenter studies to define the frequency and natural history of PSP phenotypes are missing. In a cohort of 100 autopsy-confirmed patients we studied the phenotypic spectrum of PSP by retrospective chart review. Patients were derived from five brain banks with expertise in neurodegenerative disorders with referrals from multiple academic hospitals. The clinical characteristics of the 100 cases showed remarkable heterogeneity. Most strikingly, only 24% of cases presented as Richardson's Syndrome (RS), and more than half of the cases either showed overlapping features of several predescribed phenotypes, or features not fitting proposed classification criteria for PSP phenotypes. Classification of patients according to predominant clinical features in the first 2 years of the disease course allowed a more comprehensive description of the phenotypic spectrum. These predominance types differed significantly with regard to survival time and frequency of cognitive deficits. In summary, the phenotypic spectrum of PSP may be broader and more variable than previously described in single-center studies. Thus, too strict clinical criteria defining distinct phenotypes may not reflect this variability. A more pragmatic clinical approach using predominance types could potentially be more helpful in the early recognition of and for making prognostic predictions for these patients. Given the limitations arising from the retrospective nature of this analysis, a systematic validation in a prospective cohort study is imperative.

  12. Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies.

    PubMed

    Glover, Gary H; Mueller, Bryon A; Turner, Jessica A; van Erp, Theo G M; Liu, Thomas T; Greve, Douglas N; Voyvodic, James T; Rasmussen, Jerod; Brown, Gregory G; Keator, David B; Calhoun, Vince D; Lee, Hyo Jong; Ford, Judith M; Mathalon, Daniel H; Diaz, Michele; O'Leary, Daniel S; Gadde, Syam; Preda, Adrian; Lim, Kelvin O; Wible, Cynthia G; Stern, Hal S; Belger, Aysenil; McCarthy, Gregory; Ozyurt, Burak; Potkin, Steven G

    2012-07-01

    This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.

  13. A multi-center randomized trial of two different intravenous fluids during labor

    PubMed Central

    DAPUZZO-ARGIRIOU, Lisa M.; SMULIAN, John C.; ROCHON, Meredith L.; GALDI, Luisa; KISSLING, Jessika M.; SCHNATZ, Peter F.; RIOS, Angel GONZALEZ; AIROLDI, James; CARRILLO, Mary Anne; MAINES, Jaimie; KUNSELMAN, Allen R.; REPKE, John; LEGRO, Richard S.

    2017-01-01

    Objective To determine if the intrapartum use of a 5% glucose-containing intravenous solution decreases the chance of a cesarean delivery for women presenting in active labor. Methods This was a multi-center, prospective, single (patient) blind, randomized study design implemented at 4 obstetric residency programs in Pennsylvania. Singleton, term, consenting women presenting in active spontaneous labor with a cervical dilation of <6cm were randomized to lactated Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance intravenous fluid. The primary outcome was the cesarean birth rate. Secondary outcomes included labor characteristics, as well as maternal or neonatal complications. Results There were 309 women analyzed. Demographic variables and admitting cervical dilation were similar among study groups. There was no significant difference in the cesarean delivery rate for the D5LR group (23/153 or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95%CI) of 1.32 (0.75, 2.35), P=0.34]. There were no differences in augmentation rates or intrapartum complications. Conclusions The use of intravenous fluid containing 5% dextrose does not lower the chance of cesarean delivery for women admitted in active labor. PMID:25758624

  14. Prospective study of attitudinal and relationship predictors of sexual risk in the multicenter AIDS cohort study.

    PubMed

    Ostrow, David G; Silverberg, Michael J; Cook, Robert L; Chmiel, Joan S; Johnson, Lisette; Li, Xiuhong; Jacobson, Lisa P

    2008-01-01

    We examined the influence of attitudes concerning HIV transmission, safe sex, and sexual sensation seeking, as well as negotiated risk reduction with primary partners, on the proportion of unprotected sexual partners (%UASP) among men who have sex with men (MSM). Participants were 263 HIV-seropositive and 238 HIV-seronegative MSM in the Multicenter AIDS Cohort Study between 1999 and 2003 who completed a 20-item attitude survey twice. Behavioral data were collected concurrently and 6-12 months after each survey. Among seropositives, decreased HIV concern and increased safer sex fatigue were associated with higher %UASP at 6 and 12 months. Among seronegatives, increased %UASP at 12 months was associated with safer sex fatigue. At 6 months and 12 months, risk reduction agreements were associated with increased %UASP among seronegatives in seroconcordant monogamous relationships, reflecting their abandonment of condoms in such partnerships. We conclude that HIV prevention efforts should target modifiable attitudes (reduced concern about HIV and safer sex fatigue) and increases in sexual risk-taking of MSM, particularly among HIV+ men having sex with serodiscordant partners.

  15. Repair or observe moderate ischemic mitral regurgitation during coronary artery bypass grafting? Prospective randomized multicenter data

    PubMed Central

    Gulack, Brian C.; Englum, Brian R.; Castleberry, Anthony W.; Daneshmand, Mani A.; Perrault, Louis P.

    2015-01-01

    Ischemic mitral regurgitation (MR) is a common occurrence following myocardial infarction and its presence is associated with poor outcomes. The optimal treatment of ischemic MR is a matter of debate, especially for patients with moderate MR severity. Some authors advocate for isolated coronary artery bypass grafting (CABG) for patients with moderate MR, maintaining that reverse ventricular remodeling will reduce MR grade and its associated mortality risk, while others argue that a concomitant mitral valve repair (MVR) or replacement is superior. The Cardiothoracic Surgical Trials Network (CTSN) recently published the 1-year results of the Surgical Treatment of Moderate Ischemic Mitral Regurgitation study, a multicenter, randomized, controlled trial investigating the impact of MVR in addition to CABG compared to CABG alone in the treatment of moderate ischemic MR. Here, we have reviewed previous observational and prospective studies investigating moderate ischemic MR treatment as well as the results of the current CTSN randomized trial. Furthermore, we have summarized the current state of the available evidence and preview potential new information that will become available with planned subgroup analyses and further follow-up of enrolled patients in the recently completed CTSN trial. PMID:26309829

  16. Seizures in juvenile Huntington's disease: frequency and characterization in a multicenter cohort.

    PubMed

    Cloud, Leslie J; Rosenblatt, Adam; Margolis, Russel L; Ross, Christopher A; Pillai, Jagan A; Corey-Bloom, Jody; Tully, Hannah M; Bird, Thomas; Panegyres, Peter K; Nichter, Charles A; Higgins, Donald S; Helmers, Sandra L; Factor, Stewart A; Jones, Randi; Testa, Claudia M

    2012-12-01

    Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required.

  17. Symptomatic retention of the patency capsule: a multicenter real life case series

    PubMed Central

    Kopylov, Uri; Nemeth, Artur; Cebrian, Alba; Wurm Johansson, Gabriele; Thorlacius, Henrik; Fernandez-Urien Sainz, Ignacio; Koulaouzidis, Anastasios; Eliakim, Rami; Toth, Ervin

    2016-01-01

    Background and aims: The patency capsule is designed to evaluate the patency of the small bowel before administration of small-bowel capsule endoscopy (SBCE) in patients at high risk of retention. The utilization of a patency capsule may be associated with a risk of symptomatic retention, but very few cases have been reported to date. The aim of our study was to describe our experience with this rare complication of a patency capsule. Methods: This was a multicenter retrospective case series. The medical records of patients who underwent a patency capsule test were scanned and all cases of symptomatic retention were collected. Results: In total, 20 symptomatic cases of retention out of 1615 (1.2 %) patency capsule tests were identified; in one patient, the patency capsule was retained in the esophagus, in the rest, the capsule was detected in the small bowel resulting in abdominal pain or small-bowel obstruction. One patient (5 %) required surgery; all other patients resolved spontaneously or after corticosteroid therapy. Conclusions: Symptomatic patency capsule retention is a very rare complication with a favorable prognosis. It should be recognized but its use in patients with suspected small-bowel stenosis should not be discouraged. PMID:27652302

  18. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study

    PubMed Central

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m2 and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox’s analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46–1.91) and 1% (HR = 1.01, 95% CI: 1.01–1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  19. Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study

    PubMed Central

    Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha; Reynolds, Sandra; Aronow, Aaron; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Selnes, Ola A

    2015-01-01

    The Multicenter AIDS Cohort Study (MACS) is one of the largest and longest running studies of the natural and treated history of HIV disease. The Neuropsychological (NP) substudy was begun in 1988 following reports of significant adverse neurological consequences of HIV disease, including dementia. The goal was to characterize the neuropsychological deficits among individuals with HIV disease, and track the natural history of the neurological complications over time. There were three distinct MACS recruitment stages that focused on different groups of HIV-infected men, or men at risk for infection. Initially, a subcohort was evaluated semi-annually with NP tests but, beginning in 2005, the entire group of MACS participants have had NP examinations biannually, unless closer follow-up was warranted. The participants complete a battery of NP tests, and are classified as either normal, mildly or severely impaired using the Antinori criteria for HIV-Associated Neurocognitive Disorder (HAND). Additional behavioural data, including mood state and psychoactive substance use, are recorded as part of the main MACS data collection. The MACS public data set (PDS) has been available since 1994 and includes baseline and 6-monthly follow-up data. Beginning in October 1995, the PDS has been released annually with new releases superseding previous versions. PMID:24771276

  20. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.

    PubMed

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.

  1. WIDEN: A tool for medical image management in multicenter clinical trials.

    PubMed

    Chauvie, Stéphane; Biggi, Alberto; Stancu, Alexandru; Cerello, Piergiorgio; Cavallo, Anna; Fallanca, Federico; Ficola, Umberto; Gregianin, Michele; Guerra, Ugo Paolo; Chiaravalloti, Agostino; Schillaci, Orazio; Gallamini, Andrea

    2014-06-01

    Background It has been proposed that in clinical trials in which the therapeutic strategy is driven by functional imaging, central review of the images should be done in real time. Purpose We report our experience with a new tool for image exchange and review, called Web-Based Imaging Diagnosis by Expert Network (WIDEN), which we implemented for the HD0607 prospective multicenter Italian clinical trial in which Hodgkin lymphoma treatment was adapted based on results of an interim positron emission tomography (PET) scan performed after the first two cycles of chemotherapy. Methods We used WIDEN for general management of the clinical trial, site imaging qualification, image exchange, workflow control, blinded independent central review, inter-observer variability assessment, consensus creation, audit, and statistical analysis. Results As of February 2013, the interim PET was available for 512 patients; upon central review, 103 of the scans were judged to be positive and 409 to be negative. The median scan uploading and downloading times were 1 min, 25 s and 1 min, 55 s, respectively; the average and median times for diagnosis exchange were 47 h, 53 min and 37 h, 43 min, respectively. The binary concordance between pairs of reviewers (Cohen's kappa) ranged from 0.72 to 0.85. The 5-point scale concordance among all reviewers (Krippendorf's alpha) was 0.77. Conclusions WIDEN proved to be an effective tool for medical imaging exchange and online review. Data security, simplicity, feasibility, and prompt scan review were demonstrated. Central reviews were completed promptly.

  2. Multicenter survey on the use of device-assisted enteroscopy in Portugal

    PubMed Central

    Mascarenhas-Saraiva, Miguel; Mão-de-Ferro, Susana; Ferreira, Sara; Almeida, Nuno; Figueiredo, Pedro; Rodrigues, Adélia; Cardoso, Hélder; Marques, Margarida; Rosa, Bruno; Cotter, José; Vilas-Boas, Germano; Cardoso, Carla; Salgado, Marta; Marcos-Pinto, Ricardo

    2015-01-01

    Background Device-assisted enteroscopies (DAEs) are recent endoscopic techniques that enable direct endoscopic small-bowel evaluation. Objective The objective of this article is to evaluate the implementation of DAEs in Portugal and assess the main indications, diagnoses, diagnostic yield, therapeutic yield and complication rate. Methods We conducted a multicenter retrospective series using a national Web-based survey on behalf of the Portuguese Small-Bowel Study Group. Participants were asked to fill out two online databases regarding procedural data, indications, diagnoses, endoscopic therapy and complications using prospectively collected institutional data records. Results A total of eight centers were enrolled in the survey, corresponding to 1411 DAEs. The most frequent indications were obscure gastrointestinal bleeding (OGIB), inflammatory bowel disease and small-bowel tumors. The pooled diagnostic yield was 63%. A relation between the diagnostic yield and the indications was clear, with a diagnostic yield for OGIB of 69% (p = 0.02) with a 52% therapeutic yield. Complications occurred in 1.2%, with a major complication rate of 0.57%. Perforations occurred in four patients (0.28%). Conclusion DAEs are safe and effective procedures, with complication rates of 1.2%, the most serious of which is perforation. Most procedures are performed in the setting of OGIB. Diagnostic and therapeutic yields are dependent on the indication, hence appropriate patient selection is crucial. PMID:27087956

  3. Clinical Characteristics and Prognostic Factors in Childhood Bacterial Meningitis: A Multicenter Study

    PubMed Central

    Türel, Özden; Yıldırım, Canan; Yılmaz, Yüksel; Külekçi, Sezer; Akdaş, Ferda; Bakır, Mustafa

    2013-01-01

    Objective: To evaluate clinical features and sequela in children with acute bacterial meningitis (ABM). Study Design: Multicenter retrospective study. Material and Methods: Study includes retrospective chart review of children hospitalised with ABM at 11 hospitals in İstanbul during 2005. Follow up visits were conducted for neurologic examination, hearing evaluation and neurodevelopmental tests. Results: Two hundred and eighty three children were included in the study. Median age was 12 months and 68.6% of patients were male. Almost all patients had fever at presentation (97%). Patients younger than 6 months tended to present with feeding difficulties (84%), while patients older than 24 months were more likely to present with vomitting (93%) and meningeal signs (84%). Seizures were present in 65 (23%) patients. 26% of patients were determined to have at least one major sequela. The most common sequelae were speech or language problems (14.5%). 6 patients were severely disabled because of meningitis. Presence of focal neurologic signs at presentation and turbid cerebrospinal fluid appearance increased sequelae significantly. Childen under 24 months of age developed neurologic sequelae more commonly than older children. Conclusion: Symptoms and signs were largely depending on the age of the patient. Speech or language problems were the most common sequelae following meningitis. PMID:25207074

  4. Alveolar Ridge Reconstruction with Titanium Meshes and Simultaneous Implant Placement: A Retrospective, Multicenter Clinical Study.

    PubMed

    Zita Gomes, Raquel; Paraud Freixas, Andres; Han, Chang-Hun; Bechara, Sohueil; Tawil, Isaac

    2016-01-01

    Objective. To evaluate horizontal bone gain and implant survival and complication rates in patients treated with titanium meshes placed simultaneously with dental implants and fixed over them. Methods. Twenty-five patients treated with 40 implants and simultaneous guided bone regeneration with titanium meshes (i-Gen®, MegaGen, Gyeongbuk, Republic of Korea) were selected for inclusion in the present retrospective multicenter study. Primary outcomes were horizontal bone gain and implant survival; secondary outcomes were biological and prosthetic complications. Results. After the removal of titanium meshes, the CBCT evaluation revealed a mean horizontal bone gain of 3.67 mm (±0.89). The most frequent complications were mild postoperative edema (12/25 patients: 48%) and discomfort after surgery (10/25 patients: 40%); these complications were resolved within one week. Titanium mesh exposure occurred in 6 patients (6/25 : 24%): one of these suffered partial loss of the graft and another experienced complete graft loss and implant failure. An implant survival rate of 97.5% (implant-based) and a peri-implant marginal bone loss of 0.43 mm (±0.15) were recorded after 1 year. Conclusions. The horizontal ridge reconstruction with titanium meshes placed simultaneously with dental implants achieved predictable satisfactory results. Prospective randomized controlled trials on a larger sample of patients are required to validate these positive outcomes.

  5. Retrospective Multicenter Study on Risk Factors for Surgical Site Infections after Appendectomy for Acute Appendicitis

    PubMed Central

    Giesen, Louis J.X.; van den Boom, Anne Loes; van Rossem, Charles C.; den Hoed, P.T.; Wijnhoven, Bas P.L.

    2016-01-01

    Background Surgical site infections (SSI) are seen in up to 5% of patients after appendectomy for acute appendicitis. SSI are associated with prolonged hospital stay and increased costs. The aim of this multicenter study was to identify factors associated with SSI after appendectomy for acute appendicitis. Methods Patients who underwent appendectomy for acute appendicitis between June 2014 and January 2015 in 6 teaching hospitals in the southwest of the Netherlands were included. Patient, diagnostic, intra-operative and disease-related factors were collected from the patients' charts. Primary outcome was surgical site infection. Multivariable logistic regression was performed to identify independent risk factors for SSI. Results Some 637 patients were included. Forty-two patients developed a SSI. In univariable analysis body temperature >38°C, CRP>65 and complex appendicitis were associated with SSI. After multivariable logistic regression with stepwise backwards elimination, complex appendicitis was significantly associated with SSI (OR 4.09; 95% CI 2.04-8.20). Appendiceal stump closure with a stapler device was inversely correlated with SSI (OR 0.40; 95% CI 0.24-0.97) Conclusions Complex appendicitis is a risk factor for SSI and warrants close monitoring postoperatively. The use of a stapler device for appendiceal stump closure is associated with a reduced risk of SSI. PMID:27631081

  6. Multicenter evaluation of the Bayer Immuno I CA 15-3 assay.

    PubMed

    Cheli, C D; Morris, D L; Kish, L; Goldblatt, J; Neaman, I; Allard, W J; Yeung, K K; Wu, A H; Moore, R; Chan, D W; Fritsche, H A; Schwartz, M K; Very, D L

    1998-04-01

    We conducted a multicenter evaluation of the analytical and clinical features of the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay pooled across four evaluation sites and three lots of reagent produced total CV < or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%). Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR 27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL); values were similar for all methods. Longitudinal monitoring of healthy women yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the analytical features, intermethod correlation, and long-term performance characteristics that are essential for longitudinal monitoring of breast cancer patients.

  7. Multicenter Study of Prevalence of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis in France ▿

    PubMed Central

    Roux, Anne-Laure; Catherinot, Emilie; Ripoll, Fabienne; Soismier, Nathalie; Macheras, Edouard; Ravilly, Sophie; Bellis, Gil; Vibet, Marie-Anne; Le Roux, Evelyne; Lemonnier, Lydie; Gutierrez, Cristina; Vincent, Véronique; Fauroux, Brigitte; Rottman, Martin; Guillemot, Didier; Gaillard, Jean-Louis

    2009-01-01

    We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The “new” species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%). PMID:19846643

  8. Histological and histomorphometric study using an ultrasonic crestal sinus grafting procedure. A multicenter case study

    PubMed Central

    Wainwright, Marcel; Pérez-Dorao, Beatriz; Serrera-Figallo, María-Angeles; Gutierrez-Perez, José-Luis; Troedhan, Angelo; Kurrek, Andreas

    2016-01-01

    Background The aim of this study was to evaluate the efficacy of a hydrodynamic ultrasonic driven transcrestal sinus grafting procedure (Intralift ®, Acteon Company, Bordeaux, France) and the use of a bovine high temperature sintered grafting material in sinus sites with less than 5 mm remaining bone height with no additional autogenous bone in order to create a sufficient recipient site for implants. Material and Methods 12 patients (16 sinus) in this multicenter case study were included. Using a crestal approach, bone under the sinus was prepared with ultrasonic tips until the Schneiderian membrane was reached. With a trumpet shaped instrument, the Schneiderian membrane was elevated. In the new created subantral space a high temperature sintered bovine grafting material was introduced (Bego Oss, BEGO Implant Systems GmbH & Co. KG, Bremen, Germany). After 6 months biopsies were taken with a trephine bur and histologies were generated following histomorphometric analysis. Results The results showed new vital bone in average of 33.4% ± 17.05%, and 43.6% ± 16.70 of bone substitute material. No signs of abnormal inflammation were observed. Conclusions This procedure (Intralift ®) allows, using a bovine material with no additional autogenous bone, new bone formation in the sinus in order to allow place implant subantraly. Key words:Bone regeneration, sinus, intralift ®, xenogenic bone graft PMID:26946203

  9. Laparoscopic versus open adhesiolysis for small bowel obstruction - a multicenter, prospective, randomized, controlled trial

    PubMed Central

    2014-01-01

    Background Laparoscopic adhesiolysis is emerging as an alternative for open surgery in adhesive small bowel obstruction. Retrospective studies suggest that laparoscopic approach shortens hospital stay and reduces complications in these patients. However, no prospective, randomized, controlled trials comparing laparoscopy to open surgery have been published. Methods/Design This is a multicenter, prospective, open label, randomized, controlled trial comparing laparoscopic adhesiolysis to open surgery in patients with computed-tomography diagnosed adhesive small bowel obstruction that is not resolving with conservative management. The primary study endpoint is the length of postoperative hospital stay in days. Sample size was estimated based on preliminary retrospective cohort, which suggested that 102 patients would provide 80% power to detect a difference of 2.5 days in the length of postoperative hospital stay with significance level of 0.05. Secondary endpoints include passage of stool, commencement of enteral nutrition, 30-day mortality, complications, postoperative pain, and the length of sick leave. Tertiary endpoints consist of the rate of ventral hernia and the recurrence of small bowel obstruction during long-term follow-up. Long-term follow-up by letter or telephone interview will take place at 1, 5, and 10 years. Discussion To the best of our knowledge, this trial is the first one aiming to provide level Ib evidence to assess the use of laparoscopy in the treatment of adhesive small bowel obstruction. Trial registration ClinicalTrials.gov identifier: NCT01867528. Date of registration May 26th 2013. PMID:25306234

  10. Multicenter Study of Antimicrobial Susceptibility of Anaerobic Bacteria in Korea in 2012

    PubMed Central

    Lee, Yangsoon; Park, Yeon-Joon; Kim, Mi-Na; Uh, Young; Kim, Myung Sook

    2015-01-01

    Background Periodic monitoring of regional or institutional resistance trends of clinically important anaerobic bacteria is recommended, because the resistance of anaerobic pathogens to antimicrobial drugs and inappropriate therapy are associated with poor clinical outcomes. There has been no multicenter study of clinical anaerobic isolates in Korea. We aimed to determine the antimicrobial resistance patterns of clinically important anaerobes at multiple centers in Korea. Methods A total of 268 non-duplicated clinical isolates of anaerobic bacteria were collected from four large medical centers in Korea in 2012. Antimicrobial susceptibility was tested by the agar dilution method according to the CLSI guidelines. The following antimicrobials were tested: piperacillin, piperacillin-tazobactam, cefoxitin, cefotetan, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, metronidazole, and tigecycline. Results Organisms of the Bacteroides fragilis group were highly susceptible to piperacillin-tazobactam, imipenem, and meropenem, as their resistance rates to these three antimicrobials were lower than 6%. For B. fragilis group isolates and anaerobic gram-positive cocci, the resistance rates to moxifloxacin were 12-25% and 11-13%, respectively. Among B. fragilis group organisms, the resistance rates to tigecycline were 16-17%. Two isolates of Finegoldia magna were non-susceptible to chloramphenicol (minimum inhibitory concentrations of 16-32 mg/L). Resistance patterns were different among the different hospitals. Conclusions Piperacillin-tazobactam, cefoxitin, and carbapemems are highly active β-lactam agents against most of the anaerobes. The resistance rates to moxifloxacin and tigecycline are slightly higher than those in the previous study. PMID:26206683

  11. VAC® therapy a therapeutic alternative in giant omphalocele treatment: a multicenter study.

    PubMed

    Binet, A; Gelas, T; Jochault-Ritz, S; Noizet, O; Bory, J P; Lefebvre, F; Belouadah, M; James-Robert, I; Aubert, D; Bouche-Pillon Persyn, M A; Poli-Merol, M L; François-Fiquet, C

    2013-12-01

    Giant omphalocele is associated to morbidity and mortality because of the strain the reintegrated herniated mass places on the hemodynamic equilibrium and breathing functions of affected infants. Currently, care management consists in a reintegration in one time or progressive reintegration. We report here a multicenter retrospective study about alternative management by VAC® therapy for giant omphaloceles. The study included three patients (1 girl, 2 boys) presenting with giant omphaloceles, born at full term in three different University Hospitals (prenatal diagnosis, normal karyotype). VAC® therapy was implemented at different times according to the cases (at Day 11, Month 1 and Month 5 after birth). The initial pressure applied was -10 mmHg progressively increased to -50 mmHg. A middle size VAC GranuFoam Silver® Dressing was used in all cases. Wound healing occurred at Month 4 for the first case, Month 6 and Month 8 for the other two. VAC® therapy is a good alternative for the care management of giant omphaloceles with more advantages especially when using prosthetic material. We also aimed at refining the most adapted indications in these specific situations, and finally we envisioned a harmonization of care for these children.

  12. Prospective, Multi-Center Evaluation of the Beckman Coulter Prostate Health Index Using WHO Calibration

    PubMed Central

    Loeb, Stacy; Sokoll, Lori J.; Broyles, Dennis L.; Bangma, Chris H.; van Schaik, Ron H.N.; Klee, George G.; Wei, John T.; Sanda, Martin G.; Partin, Alan W.; Slawin, Kevin M.; Marks, Leonard S.; Mizrahi, Isaac A.; Shin, Sanghyuk S.; Cruz, Amabelle B.; Chan, Daniel W.; Roberts, William L.; Catalona, William J.

    2014-01-01

    Purpose Reported prostate-specific antigen (PSA) values may differ substantially between assays with the Hybritech and World Health Organization (WHO) standardization. [-2]proPSA (p2PSA) and the Beckman Coulter prostate health index (phi) are newly approved serum markers, which are associated with prostate cancer risk and aggressiveness. Our objective was to study the influence of assay standardization on these markers. Materials and Methods PSA, % free PSA (%fPSA), and p2PSA were measured using the Hybritech calibration in 892 men undergoing prostate biopsy from a prospective multicenter study. Phi was calculated as: [p2PSA/ fPSA) × (square root of PSA)]. Performance characteristics of phi for prostate cancer detection were then determined using re-calculated WHO calibration PSA values. Results The median phi was significantly higher in men with prostate cancer compared to those with negative biopsies using the WHO values (47.4 vs 39.8, p<0.001). Phi offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to %fPSA or total PSA using the WHO calibration. Conclusions Phi can be calculated using Hybritech or WHO standardized assays, and significantly improved the prediction of biopsy outcome over %fPSA or PSA alone. PMID:23206426

  13. Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

    PubMed Central

    Rizzi, Massimiliano; Mazzuoli, Silvia; Regano, Nunzia; Inguaggiato, Rosa; Bianco, Margherita; Leandro, Gioacchino; Bugianesi, Elisabetta; Noè, Donatella; Orzes, Nicoletta; Pallini, Paolo; Petroni, Maria Letizia; Testino, Gianni; Guglielmi, Francesco William

    2016-01-01

    AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last three-six months. Values of Malnutrition Universal Screening Tool (MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment. PMID:27559436

  14. Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study.

    PubMed

    Heiser, Clemens; Maurer, Joachim T; Hofauer, Benedikt; Sommer, J Ulrich; Seitz, Annemarie; Steffen, Armin

    2017-02-01

    Objective Selective stimulation of the hypoglossal nerve is a new surgical therapy for obstructive sleep apnea, with proven efficacy in well-designed clinical trials. The aim of the study is to obtain additional safety and efficacy data on the use of selective upper airway stimulation during daily clinical routine. Study Design Prospective single-arm study. Setting Three tertiary hospitals in Germany (Munich, Mannheim, Lübeck). Subjects and Methods A multicenter prospective single-arm study under a common implant and follow-up protocol took place in 3 German centers (Mannheim, Munich, Lübeck). Every patient who received an implant of selective upper airway stimulation was included in this trial (apnea-hypopnea index ≥15/h and ≤65/h and body mass index <35 kg/m(2)). Before and 6 months after surgery, a 2-night home sleep test was performed. Data regarding the safety and efficacy were collected. Results From July 2014 through October 2015, 60 patients were included. Every subject reported improvement in sleep and daytime symptoms. The average usage time of the system was 42.9 ± 11.9 h/wk. The median apnea-hypopnea index was significantly reduced at 6 months from 28.6/h to 8.3/h. No patient required surgical revision of the implanted system. Conclusion Selective upper airway stimulation is a safe and effective therapy for patients with obstructive sleep apnea and represents a powerful option for its surgical treatment.

  15. A multicenter study of cellulite treatment with a variable emission radio frequency system.

    PubMed

    van der Lugt, Claudia; Romero, Carmen; Ancona, Dvora; Al-Zarouni, Marwan; Perera, Joanet; Trelles, Mario A

    2009-01-01

    Radio frequency (RF) systems have been reported as producing electrothermally mediated and subcutaneous effects. The present study evaluates a new approach to treat cellulite with a bipolar RF device. The buttocks of 50 patients were treated, 10 from each of five multinational centers with a novel bipolar RF technology set at 6 J/cm(3), which changes its frequency between 0.6 and 2.4 MHz according to impedance of tissue. Twelve weekly sessions were given for 12 minutes on each buttock, with a treatment end point of 42 degrees C external skin temperature. Cellulite changes and tissue condition were assessed before and immediately after the first session, before the final 12th session, and 2 months thereafter. The patient Satisfaction Index was recorded. Objective evaluation involved clinical photography, three-dimensional optical skin surface measurement, and histological findings. Almost all patients noted improvement of cellulite and body silhouette at the final session, which slightly decreased at the 2-month assessment. Improved skin appearance was objectively detected. Histological findings following the first session showed reactive edema and lysis of adipocyte membranes, possibly implicated in the final effects achieved. The RF technology used in the present multicenter study improved the general aspect of skin and cellulite, with high patient Satisfaction Index. Maintenance sessions might lead to even better and longer-lasting results.

  16. Early and Late Retrieval of the ALN Removable Vena Cava Filter: Results from a Multicenter Study

    SciTech Connect

    Pellerin, O.; Barral, F. G.; Lions, C.; Novelli, L.; Beregi, J. P.; Sapoval, M.

    2008-09-15

    Retrieval of removable inferior vena cava (IVC) filters in selected patients is widely practiced. The purpose of this multicenter study was to evaluate the feasibility and results of percutaneous removal of the ALN removable filter in a large patient cohort. Between November 2003 and June 2006, 123 consecutive patients were referred for percutaneous extraction of the ALN filter at three centers. The ALN filter is a removable filter that can be implanted through a femoral/jugular vein approach and extracted by the jugular vein approach. Filter removal was attempted after an implantation period of 93 {+-} 15 days (range, 6-722 days) through the right internal jugular vein approach using the dedicated extraction kit after control inferior vena cavography. Following filter removal, vena cavograms were obtained in all patients. Successful extraction was achieved in all but one case. Among these successful retrievals, additional manipulation using a femoral approach was needed when the apex of the filter was close to the IVC wall in two patients. No immediate IVC complications were observed according to the postimplantation cavography. Neither technical nor clinical differences between early and late filter retrieval were noticed. Our data confirm the safety of ALN filter retrieval up to 722 days after implantation. In infrequent cases, additional endovenous filter manipulation is needed to facilitate extraction.

  17. Ultrasound shear wave elastography and liver fibrosis: A Prospective Multicenter Study

    PubMed Central

    Sande, Joyce Anyona; Verjee, Suleman; Vinayak, Sudhir; Amersi, Farin; Ghesani, Munir

    2017-01-01

    AIM To assess the accuracy of shear wave elastography (SWE) alone and in combination with aminotransferase platelet ratio index (APRI) score in the staging of liver fibrosis. METHODS A multicenter prospective study was conducted to assess the accuracy of SWE (medians) and APRI to predict biopsy results. The analysis focused on distinguishing the different stages of liver disease, namely, F0 from F1-4, F0-1 from F2-4, F0-2 from F3-4 and F0-3 from F4; F0-F1 from F2-F4 being of primary interest. The area under the receiver operating characteristic (AUROC) curve was computed using logistic regression model. The role of age, gender and steatosis was also assessed. RESULTS SWE alone accurately distinguished F0-1 from F2-4 with a high probability. The AUROC using SWE alone was 0.91 compared to 0.78 for using the APRI score alone. The APRI score, when used in conjunction with SWE, did not make a significant contribution to the AUROC. SWE and steatosis were the only significant predictors that differentiated F0-1 from F2-4 with an AUROC of 0.944. CONCLUSION Our study validates the use of SWE in the diagnosis and staging of liver fibrosis. Furthermore, the probability of a correct diagnosis is significantly enhanced with the addition of steatosis as a prognostic factor. PMID:28105257

  18. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

    PubMed Central

    Skolasky, Richard L.; Seaberg, Eric; Munro, Cynthia; Becker, James T.; Martin, Eileen; Ragin, Ann; Levine, Andrew; Miller, Eric

    2016-01-01

    Objective: To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification. Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007–2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007–2008, 2009–2010, and 2011–2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009–2010 to 2011–2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition. Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period. PMID:26718568

  19. Who donates their body to science? An international, multicenter, prospective study.

    PubMed

    Cornwall, Jon; Perry, Gary F; Louw, Graham; Stringer, Mark D

    2012-01-01

    The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of donors registering during 2010 in three different geographical locations, New Zealand, Ireland, and the Republic of South Africa, was conducted to identify donor characteristics. The 28-question survey included sections on body donation program awareness, reasons for donating, giving tendency, education, ethnicity, relationship status, occupation, religion, and political preference. Two hundred surveys (81%) were returned [New Zealand 123 (85% response rate), Republic of South Africa 41 (67%), and Ireland 36 (92%)]. Results indicate that donors share certain characteristics including reason for donating (80% cited a desire to aid medical science as the main reason for wishing to donate their body); family structure (most donors are or have been in long-term partnerships and ≥ 85% have siblings); and a higher proportion with no religious affiliation compared to their reference population. Some variations between locations were noted including donor age, the mode of program awareness, occupation, relationship status, political preference, organ donor status and with whom donors had discussed their decision to donate. This information could be important for assisting the identification of potential body donors in new and established bequest programs.

  20. Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study

    SciTech Connect

    Livraghi, Tito; Meloni, Franca; Solbiati, Luigi; Zanus, Giorgio; Collaboration: For the Collaborative Italian Group using AMICA system

    2012-08-15

    Purpose: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. Methods: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellular carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. Results: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. Conclusion: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.

  1. Risk factors for deep sternal wound infection after sternotomy: a prospective, multicenter study.

    PubMed

    1996-06-01

    Several risk factors for deep sternal wound infection after sternotomy remain unclear. To assess and compare risk factors among units, a prospective study included 1830 patients in 10 units during a 4-month period: 960 underwent coronary artery bypass grafting and 870 underwent other procedures. According to the Centers for Disease Control and Prevention definitions, 2.3% of patients (42/1830) acquired a deep sternal wound infection. Independent risk factors for deep sternal wound infection were obesity, coronary artery bypass grafting, reoperation, and postoperative inotropic support. Independent risk factors after coronary artery bypass grafting were obesity, bilateral internal thoracic artery grafting, reoperation, and postoperative inotropic support. In all five of the units usually performing bilateral internal thoracic artery graftings, this procedure was associated with high risk of deep sternal wound infection. Duration of operation was a major risk factor in comparison of the unit with the highest risk of deep sternal wound infection with the other nine units; this suggests that parameters related to the perioperative period were involved. Multicenter surveillance is useful to determine reliable risk factors for deep sternal wound infection, to define a high-risk population before operation, and to assess unit-specific risk factors.

  2. Incidence and risk factors of subsequent hip fractures in Korea: multicenter study.

    PubMed

    Lee, Kee Haeng; Kim, Ju Young; Yim, Soo Jae; Moon, Do Hyun; Choi, Geun Hong; Moon, Kyoung Ho

    2014-07-01

    This study analyzes the incidence of subsequent hip fractures and its risk factors in the northwestern region of Korea. We analyzed hip fracture patients who visited any of the 5 teaching hospitals in the Bucheon and Incheon area from January 2000 to December 2010. Medical records were reviewed and presence of subsequent hip fractures, alcohol history, marital status, live in solitude, dementia, dizziness, American society of anesthesiologists score, osteoporosis treatment after fracture, body mass index (BMI) and initial bone mineral density were analyzed. The average follow-up period was 12 months (range 1-130 months). A total of 2,546 patients (women 1,770, men 776) who had experienced hip fractures were included. Of these, subsequent hip fractures were found in 233 patients (9.2%) (women 187, men 46). Mean age at the time of the first fracture was 79.2 yr old (range 50-100 yr). The average interval between the first fracture and the subsequent hip fractures was 30.2 months (range 4 days-154 months). In this large-scale, retrospective, multicenter study, overall incidence of subsequent hip fractures is 9.2%. Independent risk factors of subsequent fracture are women, BMI<22 kg/m(2), and being unmarried.

  3. Ocular microtremor during general anesthesia: results of a multicenter trial using automated signal analysis.

    PubMed

    Heaney, Mairead; Kevin, Leo G; Manara, Alex R; Clayton, Tracey J; Timmons, Shelly D; Angel, John J; Smith, Kenneth R; Ibata, Brent; Bolger, Ciaran; Cunningham, Anthony J

    2004-09-01

    Ocular microtremor (OMT) is a fine physiologic tremor of the eye related to neuronal activity in the reticular formation of the brainstem. The frequency of OMT is suppressed by propofol and sevoflurane and predicts the response to command at emergence from anesthesia. Previous studies have relied on post hoc computer analysis of OMT wave forms or on real-time measurements confirmed visually on an oscilloscope. Our overall aim was to evaluate an automated system of OMT signal analysis in a diverse patient population undergoing general anesthesia. In a multicenter trial involving four centers in three countries, we examined the accuracy of OMT to identify the unconscious state and to predict movement in response to airway instrumentation and surgical stimulation. We also tested the effects of neuromuscular blockade and patient position on OMT. We measured OMT continuously by using the closed-eye piezoelectric technique in 214 patients undergoing extracranial surgery with general anesthesia using a variety of anesthetics. OMT decreased at induction in all patients, increased transiently in response to surgical incision or airway instrumentation, and increased at emergence. The frequency of OMT predicted movement in response to laryngeal mask airway insertion and response to command at emergence. Neuromuscular blockade did not affect the frequency of OMT but decreased its amplitude. OMT frequency was unaffected by changes in patient position. We conclude that OMT, measured by an automated signal analysis module, accurately determines the anesthetic state in surgical patients, even during profound neuromuscular blockade and after changes in patient position.

  4. Multicenter study of plasma diafiltration in patients with acute liver failure.

    PubMed

    Nakae, Hajime; Eguchi, Yutaka; Saotome, Takao; Yoshioka, Toyokazu; Yoshimura, Noriko; Kishi, Yuki; Naka, Toshio; Furuya, Tomoki

    2010-10-01

    Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.

  5. A multicenter analysis of axial femorotibial rotation after total knee arthroplasty.

    PubMed

    Dennis, Douglas A; Komistek, Richard D; Mahfouz, Mohamed R; Walker, Scott A; Tucker, Abby

    2004-11-01

    A multicenter analysis was done to determine in vivo femorotibial axial rotation magnitudes and patterns in 1,027 knees (normal knees, nonimplanted ACL-deficient knees, and multiple designs of total knee arthroplasty). All knees were analyzed using fluoroscopy and a three-dimensional computer model-fitting technique during a deep knee bend and/or gait. Normal knees showed 16.5 degrees and 5.7 degrees of internal tibial rotation during a deep knee bend and gait, respectively. Rotation magnitudes and the percent having normal axial rotation patterns decreased in all total knee arthroplasty groups during a deep knee bend. During gait, all knee arthroplasty groups had similar rotational patterns (limited magnitudes). Average axial rotational magnitudes in gait and a deep knee bend were similar among major implant categories (ie, fixed-bearing versus mobile-bearing, etc). Average values in normal knees and ACL-retaining total knee arthroplasty patients (16.5 degrees and 8.1 degrees , respectively) were higher than in groups in which the ACL was absent (< 4.0 degrees ). All total knee arthroplasty groups had at least 19% of patients have a reverse axial rotational pattern during a deep knee bend and at least 31% during gait. Normal axial rotation patterns are essential for good patellar tracking, reduction of patellofemoral shear forces, and maximization of knee flexion.

  6. Endoscopic ultrasound-guided gastrojejunostomy with a lumen-apposing metal stent: a multicenter, international experience

    PubMed Central

    Tyberg, Amy; Perez-Miranda, Manuel; Sanchez-Ocaña, Ramon; Peñas, Irene; de la Serna, Carlos; Shah, Janak; Binmoeller, Kenneth; Gaidhane, Monica; Grimm, Ian; Baron, Todd; Kahaleh, Michel

    2016-01-01

    Background: Surgical gastrojejunostomy and enteral self-expanding metal stents are efficacious for the management of gastric outlet obstruction but limited by high complication rates and short-term efficacy. Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) is a novel alternative option. Patients and methods: Patients who underwent EUS-GJ between March 2014 and September 2015 as part of a prospective multicenter registry at four academic centers in two countries were included. Technical success was defined as successful placement of a gastrojejunal lumen-apposing metal stent. Clinical success was defined as the ability of the patient to tolerate an oral diet. Post-procedural adverse events were recorded. Results: The study included 26 patients, of whom 11 (42 %) were male. Technical success was achieved in 24 patients (92 %). Clinical success was achieved in 22 patients (85 %). Of the 4 patients in whom clinical success was not achieved, 2 had persistent nausea and vomiting despite a patent EUS-GJ and required enteral feeding for nutrition, 1 died before the initiation of an oral diet, and 1 underwent surgery for suspected perforation. Adverse events, including peritonitis, bleeding, and surgery, occurred in 3 patients (11.5 %). Conclusion: EUS-GJ is an emerging procedure that has efficacy and safety comparable with those of current therapies and should hold a place as a new minimally invasive option for patients with gastric outlet obstruction. Clinical trial identification number: NCT01522573 PMID:27004243

  7. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study

    PubMed Central

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M.; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Overall, ≥1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1–6 (median: 4) actionable biomarkers per patient. After MP, patients received 1–4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC. PMID:26161408

  8. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

    PubMed

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao

    2015-03-01

    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

  9. [Multi-center study of inter-scanner difference in brain positron emission tomography].

    PubMed

    Oda, Keiichi; Sakata, Muneyuki; Nishio, Tomoyuki; Tsushima, Hiroyuki; Tanizaki, Yasuo; Kato, Seiji; Ochi, Shinji

    2012-01-01

    We showed scanner dependence of brain (18)F-FDG and (11)C-PiB images by using phantom examination with nine kinds of positron emission tomography (PET) scanners. We used two types of phantoms, cylindrical phantom with 15 cm inside diameter and three-dimensional (3D) brain phantom, and we set the body phantom on the bed to examine the effect of scatter and random coefficients from outside of the axial field of view (AFOV). Radioactivity and distance of the two phantoms were determined by a pilot study to obtain a condition similar to the clinical study. Axial uniformity was evaluated by circular region of interest (ROI) of 12 cm diameter, set in the center of the reconstruction image of the cylindrical phantom. As a result, the standardized uptake value (SUV) was lower than the true value in some scanners, and there was a scanner in which the axial uniformity was deteriorated by high radioactivity outside the AFOV. In the cylindrical phantom, the axial uniformity of the scanner was improved using the new dead-time correction method; however, it was not improved in the 3D brain phantom. Quality-controlled PET scanners are important to maintain constant levels for multicenter studies.

  10. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    PubMed Central

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  11. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values.

    PubMed

    Ozarda, Yesim; Ichihara, Kiyoshi; Barth, Julian H; Klee, George

    2013-05-01

    The reference intervals (RIs) given in laboratory reports have an important role in aiding clinicians in interpreting test results in reference to values of healthy populations. In this report, we present a proposed protocol and standard operating procedures (SOPs) for common use in conducting multicenter RI studies on a national or international scale. The protocols and consensus on their contents were refined through discussions in recent C-RIDL meetings. The protocol describes in detail (1) the scheme and organization of the study, (2) the target population, inclusion/exclusion criteria, ethnicity, and sample size, (3) health status questionnaire, (4) target analytes, (5) blood collection, (6) sample processing and storage, (7) assays, (8) cross-check testing, (9) ethics, (10) data analyses, and (11) reporting of results. In addition, the protocol proposes the common measurement of a panel of sera when no standard materials exist for harmonization of test results. It also describes the requirements of the central laboratory, including the method of cross-check testing between the central laboratory of each country and local laboratories. This protocol and the SOPs remain largely exploratory and may require a reevaluation from the practical point of view after their implementation in the ongoing worldwide study. The paper is mainly intended to be a basis for discussion in the scientific community.

  12. Cooperative, Multicentered CH/ Interaction-Controlled Supramolecular Self-Assembly Processes

    SciTech Connect

    Li, Qing; Han, Chengbo; Horton, Scott R; Fuentes-Cabrera, Miguel A; Sumpter, Bobby G; Lu, Wenchang; Bernholc, J.; Maksymovych, Petro; Pan, Minghu

    2012-01-01

    Supramolecular self-assembly on well-defined surfaces provides access to a multitude of nanoscale architectures, including clusters of distinct symmetry and size. The driving forces underlying supramolecular structures generally involve both graphoepitaxy and weak directional nonconvalent interactions. Here we show that functionalizing a benzene molecule with an ethyne group introduces attractive interactions in a 2D geometry, which would otherwise be dominated by intermolecular repulsion. Furthermore, the attractive interactions enable supramolecular self-assembly, wherein a subtle balance between very weak CH/{pi} bonding and molecule-surface interactions produces a well-defined 'magic' dimension and chirality of supramolecular clusters. The nature of the process is corroborated by extensive scanning tunneling microscopy/spectroscopy (STM/S) measurements and ab initio calculations, which emphasize the cooperative, multicenter characters of the CH/{pi} interaction. This work points out new possibilities for chemical functionalization of {pi}-conjugated hydrocarbon molecules that may allow for the rational design of supramolecular clusters with a desired shape and size.

  13. Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays.

    PubMed

    Steen, Gerard; Vermeer, Henricus J; Naus, André J M; Goevaerts, Berrie; Agricola, Pauline T; Schoenmakers, Christian H H

    2006-01-01

    The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. The H-, I- and L-indices that can be measured by the Beckman LX-20 instrument (Beckman Coulter) in serum or plasma samples are a reliable semi-quantitative measure of the size of these interferences. A survey carried out in 16 Dutch clinical laboratories on the use of these indices demonstrated that in several of these laboratories, the influence of interferences is largely underestimated. Therefore, a multicenter study was carried out in which we examined the interference of hemolysis, icterus and lipemia on 32 analytes. On the basis of biological variation, we decided on cutoff indices above which analytically significant interference exists. We found analytically significant interference by hemolysis, icterus or lipemia, in 12, 7 and 15 of the 32 analytes studied, respectively. Flagging of results on the basis of analytically significant interference, however, results in too many clinically insignificant comments. On the basis of clinical significance, we conclude that significant interference by hemolysis, icterus or lipemia is present in only 5, 6 and 12 of the analytes studied, respectively. Use of the cutoff indices presented here facilitates optimal use of the LX-20 indices to prevent reporting of wrong results due to interference.

  14. Non-invasive repeated therapeutic stimulation for aphasia recovery: a multilingual, multicenter aphasia trial.

    PubMed

    Thiel, Alexander; Black, Sandra E; Rochon, Elizabeth A; Lanthier, Sylvain; Hartmann, Alexander; Chen, Joyce L; Mochizuki, George; Zumbansen, Anna; Heiss, Wolf-Dieter

    2015-04-01

    Noninvasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used in case series and small randomized controlled trials to improve recovery from poststroke aphasia in combination with speech and language therapy. Results of these studies suggest possible clinical efficacy and an excellent safety profile. Therefore, a larger international multicenter proof-of-concept trial was launched, to directly compare the safety and efficacy of rTMS, tDCS, and sham stimulation as adjuvant therapy to speech and language therapy in subacute poststroke aphasia. In the 4 participating centers, subacute stroke patients with aphasia are randomized between 5 and 30 days after ischemic stroke to either receive rTMS, tDCS, or sham stimulation in combination with a daily 45 minutes speech and language therapy session for 10 days. Efficacy is evaluated at 1 and 30 days after the last of the 10 treatment sessions using 3 outcome measures, validated in all participating languages: Boston naming test, Token test, and verbal fluency test. Additionally, adverse events are recorded to prove safety. In this study, a total of 90 patients will be recruited, and data analysis will be completed in 2016. This is the first multilingual and multinational randomized and controlled trial in poststroke aphasia and if positive, will add an effective new strategy for early stage poststroke aphasia rehabilitation.

  15. Parasitological Clearance Rates and Drug Concentrations of a Fixed Dose Combination of Azithromycin-Chloroquine in Asymptomatic Pregnant Women with Plasmodium Falciparum Parasitemia: An Open-Label, Non-Comparative Study in Sub-Saharan Africa

    PubMed Central

    Phiri, Kamija; Kimani, Joshua; Mtove, George A.; Zhao, Qinying; Rojo, Ricardo; Robbins, Jeffery; Duparc, Stephan; Ayoub, Ayman; Vandenbroucke, Pol

    2016-01-01

    Background Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority. Methods and Findings This was an open-label, non-comparative study (NCT01103713) in 5 countries in East and sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) to assess parasitological response and drug concentrations of a single, 3-day course of four tablets of a fixed-dose combination of azithromycin-chloroquine (AZCQ) 250/155 mg given during the second or third trimester to women with asymptomatic Plasmodium falciparum parasitemia in their first or second pregnancy. Parasitemia was determined by microscopy and molecular genotyping was performed to characterize parasites relative to the baseline infection. Weekly follow-up visits took place until day 42 after first dose and additional follow-up occurred after delivery. Systemic concentrations of azithromycin (AZ), chloroquine (CQ), and the CQ metabolite, desethyl CQ (DECQ) were evaluated at Day 0 (pre-dose), at Day 2 (pre-dose, 2 and 8 hours) and randomly at Days 7 and 14. Systemic concentrations of CQ and DECQ were also measured randomly at Day 21 and Day 28. In total, 404 women were screened for eligibility and 168 were treated, 155 of whom completed the study. PCR-adjusted parasitological response in the modified intent-to-treat population at day 28 (the primary efficacy endpoint) was estimated by the Kaplan-Meier method as 99.35% (95% confidence interval [CI]: 97.76, 100.00). PCR-adjusted parasitological response remained high at day 42 (95.19%; 95% CI: 91.35, 99.03). In

  16. Clinical Effectiveness of Hymenoptera Venom Immunotherapy: A Prospective Observational Multicenter Study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity

    PubMed Central

    Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Seitz, Michael J.; Aberer, Werner; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Campi, Paolo; Darsow, Ulf; Haeberli, Gabrielle; Hawranek, Thomas; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Schmid-Grendelmeier, Peter; Severino, Maurizio; Sturm, Gunter Johannes; Treudler, Regina; Wüthrich, Brunello

    2013-01-01

    Background Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Objective Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. Methods In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. Results 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. Interpretation It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy. PMID:23700415

  17. HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL: A MULTICENTER RETROSPECTIVE STUDY.

    PubMed

    Hayakawa, Mineji; Maekawa, Kunihiko; Kushimoto, Shigeki; Kato, Hiroshi; Sasaki, Junichi; Ogura, Hiroshi; Matauoka, Tetsuya; Uejima, Toshifumi; Morimura, Naoto; Ishikura, Hiroyasu; Hagiwara, Akiyoshi; Takeda, Munekazu; Kaneko, Naoyuki; Saitoh, Daizoh; Kudo, Daisuke; Kanemura, Takashi; Shibusawa, Takayuki; Furugori, Shintaro; Nakamura, Yoshihiko; Shiraishi, Atsushi; Murata, Kiyoshi; Mayama, Gou; Yaguchi, Arino; Kim, Shiei; Takasu, Osamu; Nishiyama, Kazutaka

    2016-03-01

    Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38 mg/L)/high fibrinogen (>190 mg/dL), low D-dimer (<38 mg/L)/low fibrinogen (≤190 mg/dL), high D-dimer (≥38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (≥38 mg/L)/low fibrinogen (≤190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.

  18. Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison.

    PubMed

    Cury, Ricardo C; Kitt, Therese M; Feaheny, Kathleen; Akin, Jamie; George, Richard T

    2014-01-01

    Pharmacologic stress myocardial CT perfusion (CTP) has been reported to be a viable imaging modality for detection of myocardial ischemia compared with single-photon emission CT (SPECT) in several single-center studies. However, regadenoson-stress CTP has not previously been compared with SPECT in a multicenter, multivendor study. The rationale and design of a phase 2, randomized, cross-over study of regadenoson-stress myocardial perfusion imaging by CTP compared with SPECT are described herein. The study will be conducted at approximately 25 sites by using 6 different CT scanner models, including 64-, 128-, 256-, and 320-slice systems. Subjects with known/suspected coronary artery disease will be randomly assigned to 1 of 2 imaging procedure sequences; rest and regadenoson-stress SPECT on day 1, then regadenoson-stress CTP and rest CTP/coronary CT angiography (same acquisition) on day 2; or regadenoson-stress CTP and rest CTP/CT angiography on day 1, then rest and regadenoson-stress SPECT on day 2. The prespecified primary analysis examines the agreement rate between CTP and SPECT for detecting or excluding ischemia (≥2 or 0-1 reversible defects, respectively), as assessed by 3 independent blinded readers for each modality. Non-inferiority will be indicated if the lower boundary of the 95% CI for the agreement rate is within 0.15 of 0.78 (the observed agreement rate in the regadenoson pivotal trials). The protocol described herein will support the first evaluation of regadenoson-stress CTP by using multiple scanner types compared with SPECT.

  19. Relevance of monitoring metabolic reduction in patients with relapsed or refractory follicular and mantle cell lymphoma receiving bendamustine: a multicenter study.

    PubMed

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ishizawa, Kenichi; Ogura, Michinori; Tobinai, Kensei

    2011-02-01

    The aim of the present study was to investigate the relevance of monitoring metabolic reduction evaluated by (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT in relapsed or refractory patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) who received bendamustine. We conducted a phantom study of 18F-FDG PET/CT to ensure quality control for performing a multicenter clinical study. We analyzed 49 patients with relapsed or refractory FL and MCL who received bendamustine (120 mg/m(2)) on days 1-2 of a 21-day cycle for up to six cycles as a licensing phase II study. 18F-FDG PET/CT scans were acquired before the first and after the last cycle. In a total of 175 target lesions, the maximum perpendicular diameter (Max PD), minimum PD (Min PD), sum of the products of the Max PD (SPD), maximum standardized uptake value (SUVmax), and the percentage reduction rates of Max PD (%Max PD), SPD (%SPD) and SUVmax (%SUVmax) were evaluated for the response to treatment. The therapeutic response was assessed after the last cycle of treatment according to the revised response criteria for malignant lymphoma (revised RC). We evaluated 134 lesions in 39 patients (76%) achieving complete response (CR) and 41 lesions in 10 patients (24%) not achieving CR. The Max PD, Min PD, SPD and SUVmax of the lesions after the last cycle were significantly higher in patients with non-CR than in patients with CR. The %MPD, %SPD and %SUVmax of the lesions were significantly greater in patients with CR than in patients with non-CR (P < 0.0001). Metabolic reduction was observed in all target lesions of relapsed or refractory patients with FL and MCL who achieved CR after bendamustine therapy.

  20. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  1. Effect of a low-dose contraceptive patch on efficacy, bleeding pattern, and safety: a 1-year, multicenter, open-label, uncontrolled study.

    PubMed

    Wiegratz, Inka; Bassol, Susana; Weisberg, Edith; Mellinger, Uwe; Merz, Martin

    2014-12-01

    This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.

  2. A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol

    PubMed Central

    2013-01-01

    Background Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS. Preclinical, neonatal, and pediatric studies have indicated that angiotensin receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome. Methods/Design The Aortic Irbesartan Marfan Study (AIMS) is an investigator-led, prospective, randomized, placebo-controlled, double-blind, phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490 clinically confirmed MFS patients (aged ≥6 to ≤40 years) using the revised Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo. Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter. The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography. The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months. Discussion This is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS. Not only will this provide useful information on the safety and efficacy of ARBs in MFS, it will also provide a rationale basis for potentially lifesaving therapy for MFS patients. Trial registration ISRCTN, 90011794 PMID:24289736

  3. Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

    PubMed

    Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

    2011-12-01

    New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

  4. Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

    PubMed Central

    Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

    2013-01-01

    New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

  5. Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

    PubMed Central

    Azim, Hatem A.; Kroman, Niels; Paesmans, Marianne; Gelber, Shari; Rotmensz, Nicole; Ameye, Lieveke; De Mattos-Arruda, Leticia; Pistilli, Barbara; Pinto, Alvaro; Jensen, Maj-Britt; Cordoba, Octavi; de Azambuja, Evandro; Goldhirsch, Aron; Piccart, Martine J.; Peccatori, Fedro A.

    2013-01-01

    Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence. PMID:23169515

  6. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

    PubMed Central

    Christodoulou, C.; Melville, P.; Scherl, W.F.; Pai, L.-Y.; Muenz, L.R.; He, D.; Benedict, R.H.B.; Goodman, A.; Rizvi, S.; Schwid, S.R.; Weinstock-Guttman, B.; Westervelt, H.J.; Wishart, H.

    2011-01-01

    Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18–59 years, clinically definite multiple sclerosis (MS), and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. Results: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. Conclusions: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. Classification of evidence: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average. PMID:21519001

  7. Tetanus in adults: results of the multicenter ID-IRI study.

    PubMed

    Tosun, S; Batirel, A; Oluk, A I; Aksoy, F; Puca, E; Bénézit, F; Ural, S; Nayman-Alpat, S; Yamazhan, T; Koksaldi-Motor, V; Tekin, R; Parlak, E; Tattevin, P; Kart-Yasar, K; Guner, R; Bastug, A; Meric-Koc, M; Oncu, S; Sagmak-Tartar, A; Denk, A; Pehlivanoglu, F; Sengoz, G; Sørensen, S M; Celebi, G; Baštáková, L; Gedik, H; Dirgen-Caylak, S; Esmaoglu, A; Erol, S; Cag, Y; Karagoz, E; Inan, A; Erdem, H

    2017-03-28

    Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

  8. Multi-Center Implementation of NPR 7123.1A: A Collaborative Effort

    NASA Technical Reports Server (NTRS)

    Hall, Phillip B.; McNelis, Nancy B.

    2011-01-01

    Collaboration efforts between MSFC and GRC Engineering Directorates to implement the NASA Systems Engineering (SE) Engine have expanded over the past year to include other NASA Centers. Sharing information on designing, developing, and deploying SE processes has sparked further interest based on the realization that there is relative consistency in implementing SE processes at the institutional level. This presentation will provide a status on the ongoing multi-center collaboration and provide insight into how these NPR 7123.1A SE-aligned directives are being implemented and managed to better support the needs of NASA programs and projects. NPR 7123.1A, NASA Systems Engineering Processes and Requirements, was released on March 26, 2007 to clearly articulate and establish the requirements on the implementing organization for performing, supporting, and evaluating SE activities. In early 2009, MSFC and GRC Engineering Directorates undertook a collaborative opportunity to share their research and work associated with developing, updating and revising their SE process policy to comply and align with NPR 7123.1A. The goal is to develop instructions, checklists, templates, and procedures for each of the 17 SE process requirements so that systems engineers will be a position to define work that is process-driven. Greater efficiency and more effective technical management will be achieved due to consistency and repeatability of SE process implementation across and throughout each of the NASA centers. An added benefit will be to encourage NASA centers to pursue and collaborate on joint projects as a result of using common or similar processes, methods, tools, and techniques.

  9. Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults

    SciTech Connect

    Padovani, Laetitia . E-mail: laetitia.padovani@free.fr; Sunyach, Marie-Pierre; Perol, David; Mercier, Cedric; Alapetite, Claire; Haie-Meder, Christine; Hoffstetter, Sylvette; Muracciole, Xavier; Kerr, Christine; Wagner, Jean-Philippe; Lagrange, Jean-Leon; Maire, Jean-Philippe; Cowen, Didier; Frappaz, Didier; Carrie, Christian

    2007-06-01

    Purpose: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study. Methods and Materials: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004. Radiologists or surgeons assessed disease characteristics, such as volume and extension. Patients were classified as having either high- or standard-risk disease. Prognostic factors were analyzed. Results: Median patient age was 29 years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5- and 10-year overall survival rates were 72% and 55%. Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF). By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors. In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of {>=}34 Gy and patients treated with craniospinal doses <34 Gy plus chemotherapy. Conclusion: We report the largest series of medulloblastoma in adults. Prognostic factors were similar to those observed in children. Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF. The role of chemotherapy for this group is still unclear. A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult.

  10. Actual preoperative fasting time in Brazilian hospitals: the BIGFAST multicenter study

    PubMed Central

    de Aguilar-Nascimento, José E; de Almeida Dias, Ana L; Dock-Nascimento, Diana B; Correia, Maria Isabel TD; Campos, Antonio CL; Portari-Filho, Pedro Eder; Oliveira, Sergio S

    2014-01-01

    Background Prolonged fasting increases organic response to trauma. This multicenter study investigated the gap between the prescribed and the actual preoperative fasting times in Brazilian hospitals and factors associated with this gap. Methods Patients (18–90-years-old) who underwent elective operations between August 2011 and September 2012 were included in the study. The actual and prescribed times for fasting were collected and correlated with sex, age, surgical disease (malignancies or benign disease), operation type, American Society of Anesthesiologists score, type of hospital (public or private), and nutritional status. Results A total of 3,715 patients (58.1% females) with a median age of 49 (18–94) years from 16 Brazilian hospitals entered the study. The median (range) preoperative fasting time was 12 (2–216) hours, and fasting time was longer (P<0.001) in hospitals using a traditional fasting protocol (13 [6–216] hours) than in others that had adopted new guidelines (8 [2–48] hours). Almost 80% (n=2,962) of the patients were operated on after 8 or more hours of fasting and 46.2% (n=1,718) after more than 12 hours. Prolonged fasting was not associated with physical score, age, sex, type of surgery, or type of hospital. Patients operated on due to a benign disease had an extended duration of preoperative fasting. Conclusion Actual preoperative fasting time is significantly longer than prescribed fasting time in Brazilian hospitals. Most of these hospitals still adopt traditional rather than modern fasting guidelines. All patients are at risk of long periods of fasting, especially those in hospitals that follow traditional practices. PMID:24627636

  11. Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

    PubMed Central

    Fitzlaff, Rüdiger; Röming, Hermann; Ameis, Detlev; Heinecke, Achim; Kunsch, Steffen; Ellenrieder, Volker; Ströbel, Philipp; Schepke, Michael; Meister, Tobias

    2014-01-01

    Objectives The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). Methods This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). Results The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates. Conclusions EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. Trial Registration ClinicalTrials.gov NCT02034929. PMID:25470133

  12. Sickness behavior in feverish children is independent of the severity of fever. An observational, multicenter study

    PubMed Central

    Corrard, François; Copin, Christian; Wollner, Alain; Elbez, Annie; Derkx, Véronique; Bechet, Stéphane; Levy, Corinne; Boucherat, Michel; Cohen, Robert

    2017-01-01

    Background. Objectives Behavioral changes in a febrile child are usually considered to stem from the fever. We studied sickness behavior (SB) in terms of its clinical components and its relation to fever. Methods This observational, multicenter study included children aged 6 months to 3 years who were either febrile (fever ≥12 hours, ≥ 39°C and ≥38°C at inclusion) or non-febrile and well. The child had to have been awake for the 2 hours preceding the consultation and cared for by the parent who brought him/her to the doctor. SB was evaluated according to 6 parameters over this 2-hour period: time spent playing, distance covered, time spent seeking comfort, time spent whining or crying, time spent in a state of irritation or of anger, most distorted facial expression. Two parameters were assessed for the 24-hour period preceding the consultation: time spent sleeping and appetite. The parent reported the degree of change in these parameters compared with the usual situation, using rating scales. Results 200 febrile children (most with nonspecific upper respiratory infections) and 200 non-febrile children were included. The mean values of the 8 parameters differed significantly (p<0.001) between the 2 groups and were independent of the height of fever at inclusion in the febrile children. In the study conditions, paracetamol failed to improve SB when the child was still feverish. Conclusion The 8 parameters suggested that SB and fever are two independent manifestations that are activated simultaneously during an infection. This independence is in harmony with recommendations to treat the discomfort of SB and not the fever. PMID:28278190

  13. Radiological Insertion of Denver Peritoneovenous Shunts for Malignant Refractory Ascites: A Retrospective Multicenter Study (JIVROSG-0809)

    SciTech Connect

    Sugawara, Shunsuke; Sone, Miyuki; Arai, Yasuaki; Sakamoto, Noriaki; Aramaki, Takeshi; Sato, Yozo; Inaba, Yoshitaka; Takeuchi, Yoshito; Ueno, Teruko; Matsueda, Kiyoshi; Moriguchi, Michihisa; Tsushima, Takahiro

    2011-10-15

    Purpose: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. Methods: A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. Results: PVSs were successfully placed in all patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Conclusions: Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.

  14. Rationale and design of the Multicenter Medication Reconciliation Quality Improvement Study (MARQUIS)

    PubMed Central

    2013-01-01

    Background Unresolved medication discrepancies during hospitalization can contribute to adverse drug events, resulting in patient harm. Discrepancies can be reduced by performing medication reconciliation; however, effective implementation of medication reconciliation has proven to be challenging. The goals of the Multi-Center Medication Reconciliation Quality Improvement Study (MARQUIS) are to operationalize best practices for inpatient medication reconciliation, test their effect on potentially harmful unintentional medication discrepancies, and understand barriers and facilitators of successful implementation. Methods Six U.S. hospitals are participating in this quality improvement mentored implementation study. Each hospital has collected baseline data on the primary outcome: the number of potentially harmful unintentional medication discrepancies per patient, as determined by a trained on-site pharmacist taking a “gold standard” medication history. With the guidance of their mentors, each site has also begun to implement one or more of 11 best practices to improve medication reconciliation. To understand the effect of the implemented interventions on hospital staff and culture, we are performing mixed methods program evaluation including surveys, interviews, and focus groups of front line staff and hospital leaders. Discussion At baseline the number of unintentional medication discrepancies in admission and discharge orders per patient varies by site from 2.35 to 4.67 (mean=3.35). Most discrepancies are due to history errors (mean 2.12 per patient) as opposed to reconciliation errors (mean 1.23 per patient). Potentially harmful medication discrepancies averages 0.45 per patient and varies by site from 0.13 to 0.82 per patient. We discuss several barriers to implementation encountered thus far. In the end, we anticipate that MARQUIS tools and lessons learned have the potential to decrease medication discrepancies and improve patient outcomes. Trial

  15. The Multicenter Uveitis Steroid Treatment (MUST) Trial: Rationale, Design and Baseline Characteristics

    PubMed Central

    2010-01-01

    Purpose To describe the design and methods of the Multicenter Uveitis Steroid Treatment (MUST) Trial, and the baseline characteristics of enrolled patients. Design Baseline data from a 1:1 randomized, parallel treatment design clinical trial at 23 clinical centers comparing systemic corticosteroid therapy (and immunosuppression when indicated) to fluocinolone acetonide implant placement. Methods Eligible patients have active or recently active non-infectious intermediate, posterior, or panuveitis. The study design had 90% power (two-sided type I error rate=0.05) to detect a 7.5 letter (1.5 line) difference between groups in the mean visual acuity change between baseline and two years. Secondary outcomes include ocular and systemic complications of therapy and quality of life. Baseline characteristics include demographic and clinical characteristics, quality of life, and reading center gradings of lens and fundus photos, optical coherence tomography images, and fluorescein angiograms. Results Over three years, 255 patients were enrolled (481 eyes with uveitis). At baseline, 50% of eyes with uveitis had best-corrected visual acuity worse than 20/40 (16% worse than 20/200), with a similar distribution of reduced visual acuity for intermediate uveitis and posterior or panuveitis cases. Structural complications, including macular edema (36%) and epiretinal membrane (48%), were common. Conclusions The MUST Trial will compare fluocinolone acetonide implant versus systemic therapy for management of intermediate, posterior and panuveitis. Patients with intermediate, posterior, or panuveitis enrolled in the trial had a high burden of reduced visual acuity, cataract, macular edema and epiretinal membrane; overall quality of life was lower than expected based on visual acuity. PMID:20097325

  16. Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study

    SciTech Connect

    Cai Ling; Stauder, Michael C.; Zhang Yujing; Poortmans, Philip; Li Yexiong; Constantinou, Nicolaos; Thariat, Juliette; Kadish, Sidney P.; Nguyen, Tan Dat; Kirova, Youlia M.; Ghadjar, Pirus; Weber, Damien C.; Bertran, Victoria Tuset; Ozsahin, Mahmut; Mirimanoff, Rene-Olivier

    2012-05-01

    Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

  17. IgG4-Related Disease: Results From a Multicenter Spanish Registry

    PubMed Central

    Fernández-Codina, Andreu; Martínez-Valle, Fernando; Pinilla, Blanca; López, Cristina; DeTorres, Inés; Solans-Laqué, Roser; Fraile-Rodríguez, Guadalupe; Casanovas-Martínez, Arnau; López-Dupla, Miguel; Robles-Marhuenda, Ángel; Barragán-González, María Jesús; Cid, Maria Cinta; Prieto-González, Sergio; Brito-Zerón, Pilar; Cruces-Moreno, María Teresa; Fonseca-Aizpuru, Eva; López-Torres, Manuel; Gil, Judith; Núñez-Fernández, Manuel Jesús; Pardos-Gea, José; Salvador-Cervelló, Gonzalo

    2015-01-01

    Abstract IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients. To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients. A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis. Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses. Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent. This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD. PMID:26266361

  18. One-step surgical placement of Brånemark implants: a prospective multicenter clinical study.

    PubMed

    Becker, W; Becker, B E; Israelson, H; Lucchini, J P; Handelsman, M; Ammons, W; Rosenberg, E; Rose, L; Tucker, L M; Lekholm, U

    1997-01-01

    This prospective longitudinal multicenter study evaluated the clinical outcomes after placement and restoration of one-step Brånemark implants into the maxillae and mandibles of completely and partially edentulous patients. Six surgical treatment centers participated in this study, in which 135 implants were placed into 63 adult patients. All implants were stable after placement. The majority of implants were placed into type B bone with minimal jaw resorption and type 2 bone quality. After implant placement, standard transmucosal healing abutments were firmly placed. The average amount of time between implant placement and prosthetic abutment connection was 170 days in the maxillae and 147 days in the mandibles. To evaluate crestal bone changes caused by implant placement, a periodontal probe was used to measure midbuccally from the top of the implant cylinder to the alveolar crest; in 29 patients, 54 midbuccal bone crest sites were remeasured following prosthetic abutment connection. Crestal bone changes in mandibles and maxillae were statistically and clinically insignificant. Six implants were lost prior to loading and one implant has not been restored. No implants or restorations were lost after loading. At 1 year, the implant success rate was 95.6%. Mesiodistal radiographic measurements from 34 patients were averaged, and changes from prosthetic abutment connection to, on average, 12 months follow-up were compared. The radiographs, which were digitalized, measured from the bottom of the implant cylinder to the most coronal bone in contact with implant thread. For mandibular implants, the mean radiographic bone level at prosthetic abutment connection was 1.07 mm; after loading, it was 1.35 mm. For maxillary implants, the mean radiographic bone height at prosthetic abutment connection was 1.16 mm; after loading, it was 1.36 mm. These changes were not statistically significant. The 1-year outcomes from this patient series indicate that one-step Br

  19. Maternal near miss and death among women with severe hypertensive disorders: a Brazilian multicenter surveillance study

    PubMed Central

    2014-01-01

    Background Hypertensive disorders represent the major cause of maternal morbidity in middle income countries. The main objective of this study was to identify the prevalence and factors associated with severe maternal outcomes in women with severe hypertensive disorders. Methods This was a cross-sectional, multicenter study, including 6706 women with severe hypertensive disorder from 27 maternity hospitals in Brazil. A prospective surveillance of severe maternal morbidity with data collected from medical charts and entered into OpenClinica®, an online system, over a one-year period (2009 to 2010). Women with severe preeclampsia, severe hypertension, eclampsia and HELLP syndrome were included in the study. They were grouped according to outcome in near miss, maternal death and potentially life-threatening condition. Prevalence ratios and 95% confidence intervals adjusted for cluster effect for maternal and perinatal variables and delays in receiving obstetric care were calculated as risk estimates of maternal complications having a severe maternal outcome (near miss or death). Poisson multiple regression analysis was also performed. Results Severe hypertensive disorders were the main cause of severe maternal morbidity (6706/9555); the prevalence of near miss was 4.2 cases per 1000 live births, there were 8.3 cases of Near Miss to 1 Maternal Death and the mortality index was 10.7% (case fatality). Early onset of the disease and postpartum hemorrhage were independent variables associated with severe maternal outcomes, in addition to acute pulmonary edema, previous heart disease and delays in receiving secondary and tertiary care. Conclusions In women with severe hypertensive disorders, the current study identified situations independently associated with a severe maternal outcome, which could be modified by interventions in obstetric care and in the healthcare system. Furthermore, the study showed the feasibility of a hospital system for surveillance of severe

  20. Six-Month Multicenter Study on Invasive Infections Due to Group B Streptococci in Argentina

    PubMed Central

    Lopardo, Horacio A.; Vidal, Patricia; Jeric, Paola; Centron, Daniela; Paganini, Hugo; Facklam, Richard R.; Elliott, John

    2003-01-01

    There is little information about invasive infections by group B streptococci (GBS) and their antimicrobial susceptibilities in Latin America. We performed a prospective multicenter study to determine the serotype distribution and the antimicrobial susceptibility of GBS in Argentina. We identified 58 cases, but only 44 had sufficient data to be evaluated. Eight early-, four late-, and one fatal late, late-onset neonatal infections due to GBS were found. A total of 31 patients were adults with bacteremia, skin and soft tissue infections, osteomyelitis, arthritis, meningitis, abdominal infections, and renal abscess. Serotype III was prevalent in late-onset neonatal disease, and several serotypes (Ia/c, III, Ia, and II) were involved in early-onset neonatal infections. Serotypes II, Ia/c, III, and IV were commonly found in adults, with serotype II prevalent in younger adults (18 to 69 years old) and serotype Ia/c prevalent in elderly adults (>70 years old). The mortality rate attributable to GBS infections was 10.8%. All GBS were susceptible to penicillin and ceftriaxone. Resistance to clindamycin (1.7%), erythromycin (5.2%), azithromycin (5.2%), minocycline (69%), and tetracycline (72.4%), to high levels of kanamycin and amikacin (1.7%), and to intermediately high levels of gentamicin (1.7%) was observed. The bifunctional enzyme AAC6′-APH2" was detected in the isolate resistant to aminoglycosides, and other genetic determinants were identified in other resistant isolates: tetM and tetO in tetracycline-resistant streptococci and mefA and ermTR for efflux-mediated and inducible macrolide-lincosamide-streptogramin B-resistant streptococci, respectively. For clinical purposes and rapid and easy detection of high-level aminoglycoside-resistant GBS, a screening method that used 1,000-μg kanamycin disks is proposed. PMID:14532204

  1. Multicenter Evaluation of Clinical Diagnostic Methods for Detection and Isolation of Campylobacter spp. from Stool

    PubMed Central

    Patrick, Mary; Gonzalez, Anthony; Akin, Joshua; Polage, Christopher R.; Wymore, Kate; Gillim-Ross, Laura; Xavier, Karen; Sadlowski, Jennifer; Monahan, Jan; Hurd, Sharon; Dahlberg, Suzanne; Jerris, Robert; Watson, Renee; Santovenia, Monica; Mitchell, David; Harrison, Cassandra; Tobin-D'Angelo, Melissa; DeMartino, Mary; Pentella, Michael; Razeq, Jafar; Leonard, Celere; Jung, Carrianne; Achong-Bowe, Ria; Evans, Yaaqobah; Jain, Damini; Juni, Billie; Leano, Fe; Robinson, Trisha; Smith, Kirk; Gittelman, Rachel M.; Garrigan, Charles; Nachamkin, Irving

    2016-01-01

    The use of culture-independent diagnostic tests (CIDTs), such as stool antigen tests, as standalone tests for the detection of Campylobacter in stool is increasing. We conducted a prospective, multicenter study to evaluate the performance of stool antigen CIDTs compared to culture and PCR for Campylobacter detection. Between July and October 2010, we tested 2,767 stool specimens from patients with gastrointestinal illness with the following methods: four types of Campylobacter selective media, four commercial stool antigen assays, and a commercial PCR assay. Illnesses from which specimens were positive by one or more culture media or at least one CIDT and PCR were designated “cases.” A total of 95 specimens (3.4%) met the case definition. The stool antigen CIDTs ranged from 79.6% to 87.6% in sensitivity, 95.9 to 99.5% in specificity, and 41.3 to 84.3% in positive predictive value. Culture alone detected 80/89 (89.9% sensitivity) Campylobacter jejuni/Campylobacter coli-positive cases. Of the 209 noncases that were positive by at least one CIDT, only one (0.48%) was positive by all four stool antigen tests, and 73% were positive by just one stool antigen test. The questionable relevance of unconfirmed positive stool antigen CIDT results was supported by the finding that noncases were less likely than cases to have gastrointestinal symptoms. Thus, while the tests were convenient to use, the sensitivity, specificity, and positive predictive value of Campylobacter stool antigen tests were highly variable. Given the relatively low incidence of Campylobacter disease and the generally poor diagnostic test characteristics, this study calls into question the use of commercially available stool antigen CIDTs as standalone tests for direct detection of Campylobacter in stool. PMID:26962088

  2. DICOM for Clinical Research: PACS-Integrated Electronic Data Capture in Multi-Center Trials.

    PubMed

    Haak, Daniel; Page, Charles-E; Reinartz, Sebastian; Krüger, Thilo; Deserno, Thomas M

    2015-10-01

    Providing surrogate endpoints in clinical trials, medical imaging has become increasingly important in human-centered research. Nowadays, electronic data capture systems (EDCS) are used but binary image data is integrated insufficiently. There exists no structured way, neither to manage digital imaging and communications in medicine (DICOM) data in EDCS nor to interconnect EDCS with picture archiving and communication systems (PACS). Manual detours in the trial workflow yield errors, delays, and costs. In this paper, requirements for a DICOM-based system interconnection of EDCS and research PACS are analysed. Several workflow architectures are compared. Optimized for multi-center trials, we propose an entirely web-based solution integrating EDCS, PACS, and DICOM viewer, which has been implemented using the open source projects OpenClinica, DCM4CHEE, and Weasis, respectively. The EDCS forms the primary access point. EDCS to PACS interchange is integrated seamlessly on the data and the context levels. DICOM data is viewed directly from the electronic case report form (eCRF), while PACS-based management is hidden from the user. Data privacy is ensured by automatic de-identification and re-labelling with study identifiers. Our concept is evaluated on a variety of 13 DICOM modalities and transfer syntaxes. We have implemented the system in an ongoing investigator-initiated trial (IIT), where five centers have recruited 24 patients so far, performing decentralized computed tomography (CT) screening. Using our system, the chief radiologist is reading DICOM data directly from the eCRF. Errors and workflow processing time are reduced. Furthermore, an imaging database is built that may support future research.

  3. Medical students, spirituality and religiosity-results from the multicenter study SBRAME

    PubMed Central

    2013-01-01

    Background To evaluate the relationship between spirituality/religiosity (S/R) and the attitudes, beliefs and experiences of medical students in Brazil with respect to S/R in their undergraduate training and clinical practice. Methods SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study involving 12 Brazilian medical schools with 5950 medical students (MS). Participants completed a questionnaire that collected information on socio-demographic data and S/R in their undergraduate training and practice. Results Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women and the mean age was 22.5 years. The majority of MS believed that spirituality has an impact on patients’ health (71.2%) and that this impact was positive (68.2%). The majority also wanted to address S/R in their clinical practice (58.0%) and considered it relevant (75.3%), although nearly one-half (48.7%) felt unprepared to do so. Concerning their training, most MS reported that they had never participated in a “spirituality and health” activity (81.0%) and that their medical instructors had never or rarely addressed this issue (78.3%). The majority also believed that they should be prepared to address spiritual issues related to the health of their patients (61.6%) and that this content should be included in the medical curriculum (62.6%). Conclusion There is a large gap between MS attitudes and expectations and the S/R training that they are receiving during their undergraduate training. The majority of MS surveyed believe that patients should have their beliefs addressed and that these beliefs could have important effects on their health and the doctor-patient relationship. These results should stimulate discussion about the place that S/R training should have in the medical curriculum. PMID:24314327

  4. Kidney Dysfunction and Markers of Inflammation in the Multicenter AIDS Cohort Study

    PubMed Central

    Abraham, Alison G.; Darilay, Annie; McKay, Heather; Margolick, Joseph B.; Estrella, Michelle M.; Palella, Frank J.; Bolan, Robert; Rinaldo, Charles R.; Jacobson, Lisa P.

    2015-01-01

    Background. Human immunodeficiency virus (HIV)–infected individuals are at higher risk for chronic kidney disease than HIV-uninfected individuals. We investigated whether the inflammation present in treated HIV infection contributes to kidney dysfunction among HIV-infected men receiving highly active antiretroviral therapy. Methods. The glomerular filtration rate (GFR) was directly measured (using iohexol) along with 12 markers of inflammation in Multicenter AIDS Cohort Study participants. Exploratory factor analysis was used to identify inflammatory processes related to kidney dysfunction. The estimated levels of these inflammatory processes were used in adjusted logistic regression analyses evaluating cross-sectional associations with kidney function outcomes. Results. There were 434 HIV-infected men receiving highly active antiretroviral therapy and 200 HIV-uninfected men. HIV-infected men were younger (median age, 51 vs 53 years) and had higher urine protein-creatinine ratios (median, 98 vs 66 mg/g) but comparable GFRs (median, 109 vs 106 mL/min|1.73 m2). We found an inflammatory process dominated by markers: soluble tumor necrosis factor receptor 2, soluble interleukin 2 receptor α, soluble gp130, soluble CD27, and soluble CD14. An increase of 1 standard deviation in that inflammatory process was associated with significantly greater odds of GFR ≤90 mL/min/1.73 m2 (odds ratio, 2.0) and urine protein >200 mg/g (odds ratio, 2.3). Conclusions. Higher circulating levels of immune activation markers among treated HIV-infected men may partially explain their higher burden of kidney dysfunction compared with uninfected men. PMID:25762788

  5. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  6. Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

    PubMed

    Rouet, Audrey; Aouba, Achille; Damaj, Gandhi; Soucié, Erinn; Hanssens, Katia; Chandesris, Marie-Olivia; Livideanu, Cristina Bulai; Dutertre, Marine; Durieu, Isabelle; Grandpeix-Guyodo, Catherine; Barète, Stéphane; Bachmeyer, Claude; Soria, Angèle; Frenzel, Laurent; Fain, Olivier; Grosbois, Bernard; de Gennes, Christian; Hamidou, Mohamed; Arlet, Jean-Benoit; Launay, David; Lavigne, Christian; Arock, Michel; Lortholary, Olivier; Dubreuil, Patrice; Hermine, Olivier; Georgin-Lavialle, Sophie

    2016-06-01

    Mastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.

  7. Surgery for gastric cancer patients of age 85 and older: Multicenter survey

    PubMed Central

    Konishi, Hirotaka; Ichikawa, Daisuke; Itoh, Hiroshi; Fukuda, Kenichiro; Kakihara, Naoki; Takemura, Manabu; Okugawa, Kaori; Uchiyama, Kiyoshi; Nakata, Masashi; Nishi, Hiroshi; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Otsuji, Eigo

    2017-01-01

    AIM To investigate the surgical therapies for gastric cancer (GC) patients of age 85 or older in a multicenter survey. METHODS Therapeutic opportunities for elderly GC patients have expanded in conjunction with extended life expectancy. However, the number of cases encountered in a single institution is usually very small and surgical therapies for elderly GC patients have not yet been standardized completely. In the present study, a total of 134 GC patients of age 85 or older who underwent surgery in 9 related facilities were retrospectively investigated. The relationships between surgical therapies and clinicopathological or prognostic features were analyzed. RESULTS Eighty-nine of the patients (66%) presented with a comorbidity, and 26 (19% overall) presented with more than two comorbidities. Radical lymphadenectomy was performed in 59 patients (44%), and no patient received pre- or post-operative chemotherapy. Forty of the patients (30%) experienced perioperative complications, but no surgical or perioperative mortality occurred. Laparoscopic surgery was performed in only 12 of the patients (9.0%). Univariate and multivariate analyses of the 113 patients who underwent R0 or R1 resection identified the factors of pT3/4 and limited lymphadenectomy as predictive of worse prognosis (HR = 4.68, P = 0.02 and HR =2.19, P = 0.05, respectively). Non-cancer-specific death was more common in cStage I patients than in cStage II or III patients. Limited lymphadenectomy correlated with worse cancer-specific survival (P = 0.01), particularly in cStage II patients (P < 0.01). There were no relationships between limited lymphadenectomy and any comorbidities, except for cerebrovascular disease (P = 0.07). CONCLUSION Non-cancer-specific death was not negligible, particularly in cStage I, and gastrectomy with radical lymphadenectomy appears to be an effective treatment for cStage II elderly GC patients. PMID:28275301

  8. Multicenter Comparison of Three Different Analytical Systems for Evaluation of DNA Banding Patterns from Cryptococcus neoformans

    PubMed Central

    Cardinali, Gianluigi; Martini, Alessandro; Preziosi, Roberta; Bistoni, Francesco; Baldelli, Franco

    2002-01-01

    The enormous improvement of molecular typing techniques for epidemiological and clinical studies has not always been matched by an equivalent effort in applying optimal criteria for the analysis of both phenotypic and molecular data. In spite of the availability of a large collection of statistical and phylogenetic methods, the vast majority of commercial packages are limited by using only the unweighted pair group method with arithmetic mean algorithm to construct trees and by considering electrophoretic pattern only as migration distances. The latter method has serious drawbacks when different runs (separate gels) of the same molecular analysis are to be compared. This work presents a multicenter comparison of three different systems of banding pattern analysis on random amplified polymorphic DNA, (GACA)4, and contour-clamped homogeneous electric field patterns from strains of Cryptococcus neoformans var. neoformans isolated in different clinical and geographical situations and a standard Saccharomyces cerevisiae strain employed as an outgroup. The systems considered were evaluated for their actual ability to(i) recognize identities, (ii) define complete differences (i.e., the ability to place S. cerevisiae out of the C. neoformans cluster), and (iii) estimate the extent of similarity among different strains. The ability to cluster strains according to the patient from which they were isolated was also evaluated. The results indicate that different algorithms do indeed produce divergent trees, both in overall topology and in clustering of individual strains, thus suggesting that care must be taken by individual investigators to use the most appropriate procedure and by the scientific community in defining a consensus system. PMID:12037071

  9. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration.

    PubMed

    Dolton, Michael J; Ray, John E; Chen, Sharon C-A; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-11-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P < 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P < 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P < 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (P < 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure

  10. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  11. Multicenter study on the prognosis associated with respiratory support for children with acute hypoxic respiratory failure.

    PubMed

    Guo, Fei; Hao, Lin; Zhen, Qing; Diao, Min; Zhang, Chonglin

    2016-11-01

    The objective of the present study was to explore the factors influencing the outcomes related to respiratory support of children with acute hypoxic respiratory failure (AHRF) in 30 hospitals. This was a non-controlled prospective and collaborative multicenter clinical study conducted from June, 2010 to May, 2011 (each hospital for 12 consecutive months). Children aged from 29 days to 6 years and who met the diagnostic standards of AHRF were enrolled as subjects for the study. After patients were enrolled, general parameters including disease diagnosis, treatment and prognosis were recorded. Then we analyzed the differences in prognosis and respiratory therapy of patients with AHRF. During the study period, 13,906 cases of AHRF were admitted among the 30 hospitals, accounting for 75.3% of the total number of patients with AHRF. The proportion in different hospitals ranged from 16 to 98%. A total of 492 children with hypoxic respiratory failure were admitted among the 30 hospitals. The prevalence rate was 3.54%, and the incidence of AHRF in each hospital was 4.54%. Tidal volume and respiratory support treatment were compared with the results from a 2006 study, and the differences were statistically significant in positive end-expiratory pressure (5 vs. 4, P=0.018), fraction of inspire O2 (0.5 vs. 0.4, P<0.001), pressure of artery O2 (70 vs. 60 mmHg, P<0.001) and peak inspiratory pressure (20 vs. 24 cm H2Ο, P<0.001). In conclusion, academic background and the level of regional economic development are factors which influence the prognosis of children with AHRF. On the basis of unapparent differences between academic background and the level of regional economic development, there is a substantial difference in the prognosis from different forms of respiratory support management for AHRF. Therefore, it is essential to develop respiratory support and the level of critical management of pediatric intensive care units.

  12. Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B

    PubMed Central

    Rigatto, Maria Helena; Oliveira, Maura S.; Perdigão-Neto, Lauro V.; Levin, Anna S.; Carrilho, Claudia M.; Tanita, Marcos Toshiyuki; Tuon, Felipe F.; Cardoso, Douglas E.; Lopes, Natane T.

    2016-01-01

    Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P < 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48; P < 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations. PMID:26856846

  13. Limiting loss to follow-up in a multicenter randomized trial in orthopedic surgery.

    PubMed

    Sprague, Sheila; Leece, Pamela; Bhandari, Mohit; Tornetta, Paul; Schemitsch, Emil; Swiontkowski, Marc F

    2003-12-01

    Even the best-designed, randomized controlled trials suffer when patients are lost to follow-up. Incomplete follow-up biases the results of a trial when patients who drop out are different from those who complete follow-up. This is exaggerated further when there are differential dropout rates between study groups. Previous randomized controlled trials in orthopedic trauma have reported up to 28% loss to follow-up. Only by striving to achieve a 0% loss to follow-up rate can we be certain that this type of bias does not affect our results. In our ongoing multicenter, randomized controlled trial comparing reamed and nonreamed intramedullary nailing of tibial shaft fractures, we have implemented several innovative strategies to minimize loss to follow-up. The exclusion criteria and consent process are designed to minimize losses. Study staff are carefully trained in communication and negotiation with patients. Additionally, a central methods center monitors all patient follow-up and aids in finding lost patients. Through these primary, secondary, and tertiary interventions, we have achieved 94% complete 1-year follow-up for the first 440 patients enrolled in the trial. Eleven patients withdrew consent, and we are unable to locate 17 patients. We have successfully minimized the loss to follow-up rate in our trial by incorporating innovative prevention and retention strategies into its design and conduct. Through planning, organization, and committing time and resources to minimizing loss to follow-up, other orthopedic trauma trials can hope to achieve the same high rates of follow-up.

  14. Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

    PubMed

    Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

    2004-01-01

    The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

  15. Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey.

    PubMed

    Kahwage, Paola Pinheiro; Ferriani, Mariana Paes Leme; Furtado, João M; de Carvalho, Luciana Martins; Pileggi, Gecilmara Salviato; Gomes, Francisco Hugo Rodrigues; Terreri, Maria Teresa; Magalhães, Claudia Saad; Pereira, Rosa Maria Rodrigues; Sacchetti, Silvana Brasilia; Marini, Roberto; Bonfá, Eloisa; Silva, Clovis Artur; Ferriani, Virgínia Paes Leme

    2017-03-01

    The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4-519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.

  16. Dairy-Rich Diets Augment Fat Loss on an Energy-Restricted Diet: A Multicenter Trial

    PubMed Central

    Zemel, Michael B.; Teegarden, Dorothy; Loan, Marta Van; Schoeller, Dale A.; Matkovic, Velimir; Lyle, Roseann M.; Craig, Bruce A.

    2009-01-01

    A 12-week randomized controlled multi-center clinical trial was conducted in 106 overweight and obese adults. Diets were designed to produce a 2,093 kJ/day energy deficit with either low calcium (LC; ~600 mg/day), high calcium (HC; ~1,400 mg/day), or high dairy (HD; three dairy servings, diet totaling ~1,400 mg/day). Ninety-three subjects completed the trial, and 68 met all a priori weekly compliance criteria. Both HC and HD contained comparable levels of calcium, but HC was only ~30% as effective as HD in suppressing 1,25-(OH)2D and exerted no significant effects on weight loss or body composition compared to LC. In the group that met compliance criteria, HD resulted in ~two-fold augmentation of fat loss compared to LC and HC (HD: -4.43 ± 0.53 kg; LC: -2.69 ± 0.0.53 kg; HC: -2.23 ± 0.73kg, p < 0.025); assessment of all completers and an intent-to-treat analysis produced similar trends. HD augmentated central (trunk) fat loss (HD: -2.38 ± 0.30 kg; HC: -1.42 ± 0.30 kg; LC: -1.36 ± 0.42 kg, p < 0.05) and waist circumference (HD: -7.65 ± 0.75 cm; LC: -4.92 ± 0.74 cm; LC: -4.95 ± 1.05 cm, p < 0.025). Similar effects were noted among all subjects completing the study and in an intent-to-treat analysis. These data indicate that dairy-rich diets augment weight loss by targeting the fat compartment during energy restriction. PMID:22253969

  17. Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics

    PubMed Central

    Rossetti, Luca; Digiuni, Maurizio; Giovanni, Montesano; Centofanti, Marco; Fea, Antonio M.; Iester, Michele; Frezzotti, Paolo; Figus, Michele; Ferreras, Antonio; Oddone, Francesco; Tanga, Lucia; Rolle, Teresa; Battaglino, Valentina; Posarelli, Chiara; Motolese, Ilaria; Mittica, Pietro; Bagaglia, Simone Alex; Menicacci, Cristina; De Cilla’, Stefano; Autelitano, Alessandro; Fogagnolo, Paolo

    2015-01-01

    Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (‘controls’). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1–25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age. PMID:26302445

  18. Satisfaction and expectations of patients with inflammatory bowel disease on biologic therapy: a multicenter study

    PubMed Central

    Guarini, Alessandra; Biagini, Silvia; Capaldi, Antonella; Carretto, Daniela; Angelis, Anna De; Iudice, Salvatore; Martino, Giuseppina; Marziali, Barbara; Mattiola, Roberta; Ongarelli, Cristina; Onidi, Francesca Maria; Prinzio, Manuela; Puthiavettil, Reetha; Sardi, Romina; Schiavoni, Elisa; Sinatora, Rita; Zullo, Angelo

    2017-01-01

    Background The satisfaction perceived by patients with chronic diseases affects clinical outcomes and healthcare costs. Some patients with inflammatory bowel disease (IBD) develop a more severe form requiring biologic therapy. We assessed the quality of care perceived by IBD patients in dedicated centers. Methods This prospective, cross-sectional, multicenter study enrolled consecutive IBD patients who underwent biologic therapy in the participating centers. The nurses directly involved in the management of these patients explained the rationale of the survey, provided a specific questionnaire (CACHE), and collected data. The CACHE included 31 items structured in 6 domains: staff care, clinician care, center facilities, patient information, accessibility, and patient support. Patients’ satisfaction score for each domain ranged from 0 to 100%. Results Sixteen different Italian centers participated and a total of 450 patients were enrolled (283 with Crohn’s disease and 167 with ulcerative colitis). The overall score was 82.2±19.6, satisfaction with the clinicians care scoring the highest (87.6±3.2) and the information provided to the patient scoring the lowest (70.7±7.9). More specifically, it emerged that 5.2-19.5% of patients were unsatisfied with: 1) the communication between the IBD medical team and primary care physicians; 2) information received about the disease or patients’ associations; and 3) the accessibility of the center. Conclusion Although our data revealed an acceptably high rate of global satisfaction among IBD patients receiving biologic therapy, more effort should be made to improve patient information and communication between IBD teams, other specialists and primary care physicians. PMID:28042244

  19. Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

    PubMed Central

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo; Bougma, Windtaré R.; Dorkenoo, Améyo M.; El-Setouhy, Maged; Fischer, Peter U.; Gass, Katherine; Gonzalez de Peña, Manuel; Mercado-Hernandez, Leda; Kyelem, Dominique; Lammie, Patrick J.; Flueckiger, Rebecca M.; Mwingira, Upendo J.; Noordin, Rahmah; Offei Owusu, Irene; Ottesen, Eric A.; Pavluck, Alexandre; Pilotte, Nils; Rao, Ramakrishna U.; Samarasekera, Dilhani; Schmaedick, Mark A.; Settinayake, Sunil; Simonsen, Paul E.; Supali, Taniawati; Taleo, Fasihah; Torres, Melissa; Weil, Gary J.; Won, Kimberly Y.

    2013-01-01

    Background Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. Methodology The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6–7 year olds or 1st–2nd graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. Principal Findings/Conclusions In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance

  20. Results of a multicenter study of the retrievable Tulip vena cava filter: Early clinical experience

    SciTech Connect

    Neuerburg, Joerg M.; Guenther, Rolf W.; Vorwerk, Dierk; Dondelinger, Robert F.; Jaeger, Horst; Lackner, Klaus J.; Schild, Hans H.; Plant, Graham R.; Joffre, Francis G.; Schneider, Pierre A.; Janssen, Johan H. A.

    1997-01-15

    Purpose. To evaluate clinically a new, retrievable vena caval filter in a multicenter study. Methods. The Tulip filter is a stainless steel half-basket that is suitable for antegrade or retrograde insertion via an 8.5 Fr introducer sheath. The filter can be retrieved via the jugular approach using an 11 Fr coaxial retrieval system. Forty-eight filters were implanted via the femoral approach and 38 via the jugular approach in 83 patients. Follow-up examinations (plain films, colorcoded duplex sonography) were performed up to 3 years after filter insertion (mean 136 days) in 75 patients. Twenty-seven patients were screened by colorcoded duplex sonography for insertion site thrombosis. Results. An appropriate filter position was achieved in all cases. Insertion problems occurred in 3 cases; these were not due to the filter design but to an imperfect prototype insertion mechanism that has now been modified (n=2) or a manipulation error (n=1). In 2 of these cases the filters were replaced percutaneously; 1 patient required venotomy for filter removal. No further complications due to filter insertion occurred. Two filters were used as temporary devices and were successfully removed after 6 and 11 days, respectively. There was 1 fatal recurrent pulmonary embolism (PE) and 2 non-fatal PE, 5 complete and 3 partial caval occlusions, and 3 caudal migrations of the filter. Insertion site venous thrombosis was not seen in the 27 patients monitored for this complication. Conclusion. Precise placement of the Tulip filter is feasible by either access route and the device appears mechanically stable. Further observations are needed to confirm that safe filter removal is practical up to 10 days after its insertion.

  1. Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial

    PubMed Central

    De Stefano, Carla; Normand, Domitille; Jabre, Patricia; Azoulay, Elie; Kentish-Barnes, Nancy; Lapostolle, Frederic; Baubet, Thierry; Reuter, Paul-Georges; Javaud, Nicolas; Borron, Stephen W.; Vicaut, Eric; Adnet, Frederic

    2016-01-01

    Background The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. Methods and Findings In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members’ experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. Conclusions Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death. PMID:27253993

  2. Written pain neuroscience education in fibromyalgia: a multicenter randomized controlled trial.

    PubMed

    van Ittersum, Miriam W; van Wilgen, C Paul; van der Schans, Cees P; Lambrecht, Luc; Groothoff, Johan W; Nijs, Jo

    2014-11-01

    Mounting evidence supports the use of face-to-face pain neuroscience education for the treatment of chronic pain patients. This study aimed at examining whether written education about pain neuroscience improves illness perceptions, catastrophizing, and health status in patients with fibromyalgia. A double-blind, multicenter randomized controlled clinical trial with 6-month follow-up was conducted. Patients with FM (n = 114) that consented to participate were randomly allocated to receive either written pain neuroscience education or written relaxation training. Written pain neuroscience education comprised of a booklet with pain neuroscience education plus a telephone call to clarify any difficulties; the relaxation group received a booklet with relaxation education and a telephone call. The revised illness perception questionnaire, Pain Catastrophizing Scale, and fibromyalgia impact questionnaire were used as outcome measures. Both patients and assessors were blinded. Repeated-measures analyses with last observation carried forward principle were performed. Cohen's d effect sizes (ES) were calculated for all within-group changes and between-group differences. The results reveal that written pain neuroscience education does not change the impact of FM on daily life, catastrophizing, or perceived symptoms of patients with FM. Compared with written relaxation training, written pain neuroscience education improved beliefs in a chronic timeline of FM (P = 0.03; ES = 0.50), but it does not impact upon other domains of illness perceptions. Compared with written relaxation training, written pain neuroscience education slightly improved illness perceptions of patients with FM, but it did not impart clinically meaningful effects on pain, catastrophizing, or the impact of FM on daily life. Face-to-face sessions of pain neuroscience education are required to change inappropriate cognitions and perceived health in patients with FM.

  3. Resection of spinal column tumors utilizing image-guided navigation: a multicenter analysis.

    PubMed

    Nasser, Rani; Drazin, Doniel; Nakhla, Jonathan; Al-Khouja, Lutfi; Brien, Earl; Baron, Eli M; Kim, Terrence T; Patrick Johnson, J; Yassari, Reza

    2016-08-01

    OBJECTIVE The use of intraoperative stereotactic navigation has become more available in spine surgery. The authors undertook this study to assess the utility of intraoperative CT navigation in the localization of spinal lesions and as an intraoperative tool to guide resection in patients with spinal lesions. METHODS This was a retrospective multicenter study including 50 patients from 2 different institutions who underwent biopsy and/or resection of spinal column tumors using image-guided navigation. Of the 50 cases reviewed, 4 illustrative cases are presented. In addition, the authors provide a description of surgical technique with image guidance. RESULTS The patient group included 27 male patients and 23 female patients. Their average age was 61 ± 17 years (range 14-87 years). The average operative time (incision to closure) was 311 ± 188 minutes (range 62-865 minutes). The average intraoperative blood loss was 882 ± 1194 ml (range 5-7000 ml). The average length of hospitalization was 10 ± 8.9 days (range 1-36 days). The postoperative complications included 2 deaths (4.0%) and 4 radiculopathies (8%) secondary to tumor burden. CONCLUSIONS O-arm 3D imaging with stereotactic navigation may be used to localize lesions intraoperatively with real-time dynamic feedback of tumor resection. Stereotactic guidance may augment resection or biopsy of primary and metastatic spinal tumors. It offers reduced radiation exposure to operating room personnel and the ability to use minimally invasive approaches that limit tissue injury. In addition, acquisition of intraoperative CT scans with real-time tracking allows for precise targeting of spinal lesions with minimal dissection.

  4. Digital pathology evaluation in the multicenter Nephrotic Syndrome Study Network (NEPTUNE).

    PubMed

    Barisoni, Laura; Nast, Cynthia C; Jennette, J Charles; Hodgin, Jeffrey B; Herzenberg, Andrew M; Lemley, Kevin V; Conway, Catherine M; Kopp, Jeffrey B; Kretzler, Matthias; Lienczewski, Christa; Avila-Casado, Carmen; Bagnasco, Serena; Sethi, Sanjeev; Tomaszewski, John; Gasim, Adil H; Hewitt, Stephen M

    2013-08-01

    Pathology consensus review for clinical trials and disease classification has historically been performed by manual light microscopy with sequential section review by study pathologists, or multi-headed microscope review. Limitations of this approach include high intra- and inter-reader variability, costs, and delays for slide mailing and consensus reviews. To improve this, the Nephrotic Syndrome Study Network (NEPTUNE) is systematically applying digital pathology review in a multicenter study using renal biopsy whole slide imaging (WSI) for observation-based data collection. Study pathology materials are acquired, scanned, uploaded, and stored in a web-based information system that is accessed through a web-browser interface. Quality control includes metadata and image quality review. Initially, digital slides are annotated, with each glomerulus identified, given a unique number, and maintained in all levels until the glomerulus disappears or sections end. The software allows viewing and annotation of multiple slide sections concurrently. Analysis utilizes "descriptors" for patterns of injury, rather than diagnoses, in renal parenchymal compartments. This multidimensional representation via WSI, allows more accurate glomerular counting and identification of all lesions in each glomerulus, with data available in a searchable database. The use of WSI brings about efficiency critical to pathology review in a clinical trial setting, including independent review by multiple pathologists, improved intraobserver and interobserver reproducibility, efficiencies and risk reduction in slide circulation and mailing, centralized management of data integrity and slide images for current or future studies, and web-based consensus meetings. The overall effect is improved incorporation of pathology review in a budget neutral approach.

  5. Prospective, multicenter evaluation of balloon sinus dilation for treatment of pediatric chronic rhinosinusitis

    PubMed Central

    Rosenbloom, Jeffrey S.; Skarada, Douglas; Gutman, Michael; Hoy, Mark J.; Nguyen, Shaun A.

    2016-01-01

    Background Although balloon sinus dilation is a treatment option for adults with chronic rhinosinusitis (CRS), there have been few studies performed in pediatric patients. Methods This study was designed as a prospective, multicenter, single‐arm investigation. Children (2 to 21 years old) with CRS who had failed medical management were treated with balloon sinus dilation and followed to 6 months postprocedure. Results Fifty children were treated at 4 centers; 33 participants were 2 to 12 years old (mean ± standard deviation age: 6.6 ± 2.2 years) and 17 participants were >12 to 21 years (mean age: 15.7 ± 2.5 years). A total of 157 sinus dilations were attempted (98 maxillary, 30 frontal, and 29 sphenoid sinuses) and all were successful with no complications. Significant improvement in the Sinus and Nasal Quality of Life Survey (SN‐5) was seen for all children between baseline and 6 months (4.6 ± 1.2 vs 1.7 ± 0.8; p < 0.0001) and 92% improved by a minimal clinically important difference (MCID) of 1.0 or more. Those children aged 2 to 12 years with standalone balloon dilation also showed significant SN‐5 improvements between baseline and follow‐up (4.5 ± 1.0 vs 1.9 ± 0.8; p < 0.0001). Multivariate regression analysis showed no differences or associations of SN‐5 improvement at 6 months with the presence of allergy, asthma, or concomitant procedures. For adolescents, overall 22‐item Sino‐Nasal Outcome Test (SNOT‐22) mean scores were also significantly improved at 6 months (42.2 ± 19.2 vs 10.4 ± 9.7; p < 0.0001). Conclusion Balloon sinus dilation is safe and appears effective for children with CRS aged 2 years and older. PMID:27888649

  6. Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

    PubMed Central

    Ríos, Antonio; López-Navas, Ana Isabel; López-López, Ana Isabel; Gómez, Francisco Javier; Iriarte, Jorge; Herruzo, Rafael; Blanco, Gerardo; Llorca, Francisco Javier; Asunsolo, Angel; Sánchez-Gallegos, Pilar; Gutiérrez, Pedro Ramón; Fernández, Ana; de Jesús, María Teresa; Martínez-Alarcón, Laura; Lana, Alberto; Fuentes, Lorena; Hernández, Juan Ramón; Virseda, Julio; Yelamos, José; Bondía, José Antonio; Hernández, Antonio Miguel; Ayala, Marco Antonio; Ramírez, Pablo; Parrilla, Pascual

    2016-01-01

    AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude. METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ2 test and logistic regression analysis. RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one's family (P < 0.001) and friends (P < 0.001); (10) a partner's opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001). CONCLUSION: Spanish medical students have a favorable attitude toward LLD. PMID:27433093

  7. A multi-center milestone study of clinical vertebral CT segmentation.

    PubMed

    Yao, Jianhua; Burns, Joseph E; Forsberg, Daniel; Seitel, Alexander; Rasoulian, Abtin; Abolmaesumi, Purang; Hammernik, Kerstin; Urschler, Martin; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Castro-Mateos, Isaac; Pozo, Jose M; Frangi, Alejandro F; Summers, Ronald M; Li, Shuo

    2016-04-01

    A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention.

  8. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

    PubMed Central

    2014-01-01

    Introduction Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). Methods A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. Results A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. Conclusions Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients. PMID:25047960

  9. Evaluation of the Informed Consent Process of a Multicenter Tuberculosis Treatment Trial

    PubMed Central

    Chapman, Kimberley N.; Pevzner, Eric; Mangan, Joan M.; Breese, Peter; Lamunu, Dorcas; Shrestha-Kuwahara, Robin; Nakibali, Joseph G.; Goldberg, Stefan V.

    2016-01-01

    and challenges were identified in obtaining consent in a large, international multicenter trial and provided insights for a more robust assessment of the consent process in future trials. PMID:28317002

  10. Mixed Membership Trajectory Models of Cognitive Impairment in the Multicenter AIDS Cohort Study

    PubMed Central

    Molsberry, Samantha A.; Lecci, Fabrizio; Kingsley, Lawrence; Junker, Brian; Reynolds, Sandra; Goodkin, Karl; Levine, Andrew J.; Martin, Eileen; Miller, Eric N.; Munro, Cynthia A.; Ragin, Ann; Sacktor, Ned; Becker, James T.

    2016-01-01

    Objective The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the “closeness” of an individual to one of the canonical trajectories. Design The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV Disease among gay and bisexual men. Methods Using data from 3,892 men (both HIV-infected and uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual’s “closeness” to these trajectories. Results We identified three distinct trajectories to cognitive impairment – one “normal aging” (low probability of mild impairment until age 60), one “premature aging” (mild impairment starting at age 45–50), and one “unhealthy” (mild impairment in 20s and 30s) profile. Second, clinically defined AIDS and not simply HIV Disease, was associated with closeness to the premature aging trajectory. And, third, Hepatitis-C infection, Depression, Race, Recruitment Cohort and Confounding Conditions all affected individual’s closeness to these trajectories. Conclusions These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment. PMID:25565498

  11. Patient-directed Internet-based Medical Image Exchange: Experience from an Initial Multicenter Implementation

    PubMed Central

    Greco, Giampaolo; Patel, Anand S.; Lewis, Sara C.; Shi, Wei; Rasul, Rehana; Torosyan, Mary; Erickson, Bradley J.; Hiremath, Atheeth; Moskowitz, Alan J.; Tellis, Wyatt M.; Siegel, Eliot L.; Arenson, Ronald L.; Mendelson, David S.

    2015-01-01

    Rationale and Objectives Inefficient transfer of personal health records among providers negatively impacts quality of health care and increases cost. This multicenter study evaluates the implementation of the first Internet-based image-sharing system that gives patients ownership and control of their imaging exams, including assessment of patient satisfaction. Materials and Methods Patients receiving any medical imaging exams in four academic centers were eligible to have images uploaded into an online, Internet-based personal health record. Satisfaction surveys were provided during recruitment with questions on ease of use, privacy and security, and timeliness of access to images. Responses were rated on a five-point scale and compared using logistic regression and McNemar's test. Results A total of 2562 patients enrolled from July 2012 to August 2013. The median number of imaging exams uploaded per patient was 5. Most commonly, exams were plain X-rays (34.7%), computed tomography (25.7%), and magnetic resonance imaging (16.1%). Of 502 (19.6%) patient surveys returned, 448 indicated the method of image sharing (Internet, compact discs [CDs], both, other). Nearly all patients (96.5%) responded favorably to having direct access to images, and 78% reported viewing their medical images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users compared to CD users reported access without difficulty (88.3% vs. 77.5%, P < 0.0001). Conclusion A patient-directed, interoperable, Internet-based image-sharing system is feasible and surpasses the use of CDs with respect to accessibility of imaging exams while generating similar satisfaction with respect to privacy. PMID:26625706

  12. Practice Patterns Regarding Management of Rectovaginal Fistulae: A Multicenter Review From the Fellows’ Pelvic Research Network

    PubMed Central

    Oakley, Susan H.; Brown, Heidi W.; Yurteri-Kaplan, Ladin; Greer, Joy A.; Richardson, Monica L.; Adelowo, Amos; Lindo, Fiona M.; Greene, Kristie A.; Fok, Cynthia S.; Book, Nicole M.; Saiz, Cristina M.; Plowright, Leon N.; Harvie, Heidi S.; Pauls, Rachel N.

    2016-01-01

    Objectives Rectovaginal fistulae (RVFs) are often debilitating and there are no established treatment algorithms. We sought to describe current diagnosis and management strategies for RVFs across the United States. Methods This institutional review board–approved multicenter retrospective study included 12 sites. Cases were identified using International Classification of Diseases, Ninth Revision codes during a 5-year period. Demographics, management, and outcomes of RVF treatment were collected. Results Three hundred forty-two charts were identified; 176 (52%) met criteria for inclusion. The mean (SD) age was 45 (17) years. Medical history included hypertension (21%), cancer (17%), Crohn disease (11%), and diabetes (7%). Rectovaginal fistulae were often associated with obstetric trauma (42%), infection/inflammation (24%), and cancer (11%). Overall, most RVFs were primary (94%), small (0.5–1.5 cm; 49%), transsphincteric (31%), and diagnosed via vaginal and rectal (60%) examination. Eighteen percent (32/176) were initially managed conservatively for a median duration of 56 days (interquartile range, 29–168) and 66% (21/32) of these resolved. Almost half (45%) of RVFs treated expectantly were tiny (<0.5 cm). Eighty-two percent (144/176) of subjects were initially managed surgically and 81% (117/144) resolved. Procedures included simple fistulectomy with or without Martius graft (59%), transsphincteric repair (23%), transverse transperineal repair (10%), and open techniques (8%), and 87% of these procedures were performed by urogynecologists. Conclusions In this large retrospective review, most primary RVFs were treated surgically, with a success rate of more than 80%. Two thirds of RVFs managed conservatively resolved spontaneously, and most of these were tiny (<0.5 cm). These success rates can be used in counseling to help our patients make informed decisions about their treatment options. PMID:25730438

  13. Multicenter Closed-Loop/Hybrid Meal Bolus Insulin Delivery with Type 1 Diabetes

    PubMed Central

    Chase, H. Peter; Doyle, Francis J.; Zisser, Howard; Renard, Eric; Nimri, Revital; Cobelli, Claudio; Buckingham, Bruce A.; Maahs, David M.; Anderson, Stacey; Magni, Lalo; Lum, John; Calhoun, Peter; Kollman, Craig

    2014-01-01

    Abstract Background: This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system. Subjects and Methods: This study was a multicenter trial in 53 patients, 12–65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4. Results: Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period). Conclusions: The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm. PMID:25188375

  14. Prospective Multicenter Study of the Impact of Carbapenem Resistance on Mortality in Pseudomonas aeruginosa Bloodstream Infections

    PubMed Central

    Suarez, Cristina; Gozalo, Mónica; Murillas, Javier; Almirante, Benito; Pomar, Virginia; Aguilar, Manuela; Granados, Ana; Calbo, Esther; Rodríguez-Baño, Jesús; Rodríguez, Fernando; Tubau, Fe; Martínez-Martínez, Luis; Oliver, Antonio

    2012-01-01

    The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities. PMID:22155832

  15. A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

    PubMed Central

    Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

    2015-01-01

    Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

  16. Estimation of the capacity of emergency surgery in Konya: Nine-year multicenter study

    PubMed Central

    Küçükkartallar, Tevfik; Çakır, Murat; Tekin, Ahmet; Balasar, Mehmet; Kartal, Adil; Köksal, Hande; Erengül, Bülent; Türk, Emin

    2016-01-01

    Objective Although the number of surgical emergencies continues to increase, comprehensive data on emergency surgical admissions are scarce. The aim of this multicenter study was to evaluate the causes, management, and outcomes of the general surgical emergencies in the city of Konya, Turkey. Material and Methods The relevant details of the cases admitted and considered to be general surgical emergencies in Konya over a nine-year period (January 2003–January 2012) were analyzed. All demographic data were analyzed statistically. Results The study group comprised 21954 cases from 4 hospitals in Konya: 7154 from Konya Numune Hospital, 6,654 from Konya Education and Research Hospital, 6,400 from Necmettin Erbakan University Meram Medical Faculty, and 1,390 from Başkent University Konya Education and Research Hospital. Their mean age was 59.6 years, and the average hospitalization time was 3.3 days. The diagnoses of the admitted patients were as follows: acute appendicitis (59.57%), bowel obstruction (11.12%), trauma (7.97%), strangulated inguinal hernia (5.46%), acute cholecystitis (4.87%), peptic ulcer perforation (4.09%), mesenteric ischemia (2.73%), necrotizing fasciitis (2.73%), gastrointestinal system bleeding (1.79%), and others (1.1%). Conclusion The findings of the study indicate a steady increase in surgical admissions to emergency units. Non-traumatic acute abdomen was the most common reason for general surgical emergencies. Although the number of elderly patients increased, the hospital stay and mortality rates decreased over the study period. PMID:28149121

  17. The Multi-Center Airborne Coherent Atmospheric Wind Sensor: Recent Measurements and Future Applications

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Howell, James N.; Darby, Lisa S.; Tratt, David M.; Menzies, Robert T.

    1999-01-01

    The coherent Doppler lidar, when operated from an airborne platform, offers a unique measurement capability for study of atmospheric dynamical and physical properties. This is especially true for scientific objectives requiring measurements in optically-clear air, where other remote sensing technologies such as Doppler radar are at a disadvantage in terms of spatial resolution and coverage. Recent experience suggests airborne coherent Doppler lidar can yield unique wind measurements of--and during operation within--extreme weather phenomena. This paper presents the first airborne coherent Doppler lidar measurements of hurricane wind fields. The lidar atmospheric remote sensing groups of National Aeronautics and Space Administration (NASA) Marshall Space Flight Center, National Oceanic and Atmospheric Administration (NOAA) Environmental Technology Laboratory, and Jet Propulsion Laboratory jointly developed an airborne lidar system, the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS). The centerpiece of MACAWS is the lidar transmitter from the highly successful NOAA Windvan. Other field-tested lidar components have also been used, when feasible, to reduce costs and development time. The methodology for remotely sensing atmospheric wind fields with scanning coherent Doppler lidar was demonstrated in 1981; enhancements were made and the system was reflown in 1984. MACAWS has potentially greater scientific utility, compared to the original airborne scanning lidar system, owing to a factor of approx. 60 greater energy-per-pulse from the NOAA transmitter. MACAWS development was completed and the system was first flown in 1995. Following enhancements to improve performance, the system was re-flown in 1996 and 1998. The scientific motivation for MACAWS is three-fold: obtain fundamental measurements of subgrid scale (i.e., approx. 2-200 km) processes and features which may be used to improve parameterizations in hydrological, climate, and general

  18. Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study

    PubMed Central

    Wynn, Julia; Aspelund, Gudrun; Zygmunt, Annette; Stolar, Charles JH.; Mychaliska, George; Butcher, Jennifer; Lim, Foong-Yen; Gratton, Teresa; Potoka, Douglas; Brennan, Kate; Azarow, Ken; Jackson, Barbara; Needelman, Howard; Crombleholme, Timothy; Zhang, Yuan; Duong, Jimmy; Arkovitz, Marc S.; Chung, Wendy K.; Farkouh, Christiana

    2013-01-01

    Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at two years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at two years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 +/− 15, 95 +/−16, and 95 +/− 11. Ten percent (5/47) scored more than two standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 +/−14, 94+/−16, 93 +/− 13, 97+/− 10, and 94 +/− 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At two years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at two years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays. PMID:24094947

  19. Management and risk factor control of coronary artery disease in elderly versus nonelderly: a multicenter registry

    PubMed Central

    Phrommintikul, Arintaya; Krittayaphong, Rungroj; Wongcharoen, Wanwarang; Boonyaratavej, Smonporn; Wongvipaporn, Chaiyasith; Tiyanon, Woraporn; Dinchuthai, Pakaphan; Kunjara-Na-Ayudhya, Rapeephon; Tatsanavivat, Pyatat; Sritara, Piyamitr

    2016-01-01

    Background Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients. Methods The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) vs. nonelderly (age < 65 years). Results There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients. Conclusions The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort. PMID:28321237

  20. Voriconazole therapeutic drug monitoring: results of a prematurely discontinued randomized multicenter trial

    PubMed Central

    Neofytos, D.; Ostrander, D.; Shoham, S.; Laverdiere, M.; Hiemenz, J.; Nguyen, H.; Clark, W.; Brass, L.; Lu, N.; Marr, K.A.

    2015-01-01

    Background Voriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs). Methods We initiated a prospective, randomized, non-blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician-driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real-time dose adjustments were made to maintain a range between 1–5 μg/mL on the TDM-arm, while levels were assessed retrospectively in the standard arm. Patient questionnaires were administered to assess subjective AEs. Results The study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard-arm, 3 TDM-arm). VOR levels were frequently out of range in the standard-arm (8 tests >5 μg/mL; 9 tests < 1 μg/mL). Three dose changes occurred in the TDM-arm for VOR levels <1 μg/mL. Levels decreased over time in the standard-arm, with mean VOR levels lower at end of therapy compared to TDM (1.3 vs. 4.6 μg/mL, P = 0.008). Conclusions VOR TDM has become widespread clinical practice, based on known variability in drug levels, which impaired accrual in this study. Although comparative conclusions are limited, observations of variability and waning levels over time support TDM. PMID:26346408

  1. Validation of the Spanish version of the hip outcome score: a multicenter study

    PubMed Central

    2014-01-01

    Background The Hip Outcome Score (HOS) is a self-reported questionnaire evaluating the outcomes of treatment interventions for hip pathologies, divided in 19 items of activities of daily life (ADL) and 9 sports’ items. The aim of the present study is to translate and validate HOS into Spanish. Methods A prospective and multicenter study with 100 patients undergoing hip arthroscopy was performed between June 2012 and January 2013. Crosscultural adaptation was used to translate HOS into Spanish. Patients completed the questionnaire before and after surgery. Feasibility, reliability, internal consistency, construct validity (correlation with Western Ontario and McMaster Universities Osteoarthritis Index), ceiling and floor effects and sensitivity to change were assessed for the present study. Results Mean age was 45.05 years old. 36 women and 64 men were included. Feasibility: 13% had at least one missing item within the ADL subscale and 17% within the sport subscale. Reliability: the translated version of HOS was highly reproducible with intraclass correlation coefficient of 0.95 for ADL and 0.94 for the sports subscale. Internal consistency was confirmed with Cronbach’s alpha >0.90 in both subscales. Construct validity showed statistically significant correlation with WOMAC. Ceiling effect was observed in 6% and 12% for ADL and sports subscale, respectively. Floor effect was found in 3% and 37% ADL and sports subscale, respectively. Large sensitivity to change was shown in both subscales. Conclusion The translated version of HOS into Spanish has shown to be feasible, reliable and sensible to changes for patients undergoing hip arthroscopy. This validated translation of HOS allows for comparisons between studies involving either Spanish- or English-speaking patients. Level of evidence Prognostic study, Level I PMID:24884511

  2. Postprescription review improves in-hospital antibiotic use: a multicenter randomized controlled trial.

    PubMed

    Lesprit, P; de Pontfarcy, A; Esposito-Farese, M; Ferrand, H; Mainardi, J L; Lafaurie, M; Parize, P; Rioux, C; Tubach, F; Lucet, J C

    2015-02-01

    Although review of antibiotic therapy is recommended to optimize antibiotic use, physicians do not always perform it. This trial aimed to evaluate the impact of a systematic postprescription review performed by antimicrobial stewardship program (ASP) infectious disease physicians (IDP) on the quality of in-hospital antibiotic use. A multicenter, prospective, randomized, parallel-group trial using the PROBE (Prospective Randomized Open-label Blinded Endpoint) methodology was conducted in eight surgical or medical wards of four hospitals. Two hundred forty-six patients receiving antibiotic therapy prescribed by ward physicians for less than 24 hours were randomized to receive either a systematic review by the ASP IDP at day 1 and days 3 to 4 (intervention group, n = 123) or no systematic review (usual care, n = 123). The primary outcome measure was appropriateness of antimicrobial therapy, a composite score of appropriateness of antibiotic use at days 3 to 4 and appropriate treatment duration, adjudicated by a blinded committee. Analyses were performed on an intention-to-treat basis. In the intervention group, appropriateness of antimicrobial therapy was more frequent (55/123, 44.7% vs. 35/123, 28.5%; odds ratio 2.03, 95% confidence interval 1.20-3.45). Antibiotic treatment duration was lower in the intervention group (median (interquartile range) 7 (3-9) days vs. 10 (7-12) days; p 0.003). ASP IDP counseling to change therapy was more frequent at days 3 to 4 than at day 1 (114/123; 92.7% vs. 24/123; 19.5%, p <0.001). Clinical outcome was similar between groups. This study suggests that a systematic postprescription antibiotic review performed at days 1 and 3 to 4 results in higher quality of antibiotic use and lower antibiotic duration. This trial was registered at ClinicalTrials.gov (NCT01136200).

  3. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multi-center study

    PubMed Central

    Gaspard, Nicolas; Foreman, Brandon; Judd, Lilith M.; Brenton, James N.; Nathan, Barnett R.; McCoy, Blathnaid M.; Al-Otaibi, Ali; Kilbride, Ronan; Fernández, Ivan Sánchez; Mendoza, Lucy; Samuel, Sophie; Zakaria, Asma; Kalamangalam, Giridhar P.; Legros, Benjamin; Szaflarski, Jerzy P.; Loddenkemper, Tobias; Hahn, Cecil D.; Goodkin, Howard P.; Claassen, Jan; Hirsch, Lawrence J.; LaRoche, Suzette M.

    2013-01-01

    Summary Purpose To examine patterns of use, efficacy and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and EEG reports in ten academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key findings Permanent control of RSE was achieved in 57% (34/60) of episodes. Ketamine was felt to have contributed to permanent control (“possible” or “likely” responses) in 32% (19/60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with post-anoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9mg/kg/h; when ketamine was introduced at least eight days after SE onset; or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26/60), but was lower when SE was controlled within 24h of ketamine initiation (16% vs. 56%, p=0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE. PMID:23758557

  4. Multicenter evaluation of the BD Phoenix Automated Microbiology System for antimicrobial susceptibility testing of Streptococcus species.

    PubMed

    Richter, Sandra S; Howard, Wanita J; Weinstein, Melvin P; Bruckner, David A; Hindler, Janet F; Saubolle, Michael; Doern, Gary V

    2007-09-01

    This multicenter study evaluated the BD Phoenix Automated Microbiology System STREP panel (BD Diagnostic Systems). Antimicrobial susceptibility testing (AST) with 13 agents was performed on 2,013 streptococci (938 Streptococcus pneumoniae isolates; 396 group B streptococci [GBS]; 369 viridans group streptococci [VGS]; 290 beta-hemolytic streptococcus groups A, C, and G; and 20 other streptococci) with the Phoenix system and a broth microdilution reference method. Clinical and challenge isolates were tested against cefepime, cefotaxime (CTX), ceftriaxone (CTR), clindamycin (CLI), erythromycin (ERY), gatifloxacin, levofloxacin, linezolid, meropenem, penicillin (PEN), tetracycline (TET), trimethoprim-sulfamethoxazole, and vancomycin. Clinical isolates with major errors or very major errors (VMEs) were retested in duplicate by both methods. The final results for clinical isolates showed the following trends. For all of the organism-antimicrobial agent combinations tested, categorical agreement (CA) was 92 to 100%, with one exception-VGS-PEN (87% CA; all errors were minor). For S. pneumoniae, there was one major error with CLI (0.1%) and one or two VMEs with CTX (4%), CTR (4.5%), ERY (0.9%), and TET (0.7%). For groups A, C, and G, the CA was 97 to 100% and the only VMEs were resolved by additional reference laboratory testing. For GBS, there was only one VME (TET, 0.3%) and D-zone testing of 23 isolates with CLI major errors (one isolate unavailable) revealed inducible CLI resistance. For VGS, the major error rates were 0 to 3% and VMEs occurred with seven agents (3.5 to 7.1%). The mean times required for organism groups to generate results ranged from 8.4 to 9.4 h. The Phoenix system provided reliable and rapid AST results for most of the organism-antimicrobial agent combinations tested.

  5. Prospective multicenter clinical evaluation of AMPLICOR and COBAS AMPLICOR hepatitis C virus tests.

    PubMed

    Nolte, F S; Fried, M W; Shiffman, M L; Ferreira-Gonzalez, A; Garrett, C T; Schiff, E R; Polyak, S J; Gretch, D R

    2001-11-01

    We conducted a multicenter clinical evaluation of the second versions of the manual AMPLICOR and the semiautomated COBAS AMPLICOR tests for hepatitis C virus (HCV) RNA (Roche Molecular Systems, Inc., Pleasanton, Calif.). The performance characteristics of these HCV RNA tests for diagnosis of active viral infection were determined by comparison to anti-HCV serological test results, alanine aminotransferase levels, and liver biopsy histology results. A total of 878 patients with clinical or biochemical evidence of liver disease were enrolled at four hepatology clinics. A total of 1,089 specimens (901 serum and 188 plasma) were tested with the AMPLICOR test. Sensitivity compared to serology was 93.1% for serum and 90.6% for plasma. The specificity was 97% for serum and 93.1% for plasma. A total of 1,084 specimens (896 serum and 188 plasma) were tested with the COBAS test. Sensitivities for serum and plasma were the same as with the AMPLICOR test. The specificity was 97.8% for serum and 96.6% for plasma. Of the 69 specimens with false-positive and false-negative AMPLICOR test results relative to those of serology, alternative primer set (APS) reverse transcription (RT)-PCR analysis showed that the AMPLICOR test provided the correct result relative to the specimens containing HCV RNA in 64 (92.7%) specimens. Similarly, 66 of 67 (98.5%) false-positive and false-negative COBAS test results were determined to be correct by APS RT-PCR analysis. There were no substantive differences in clinical performances between study sites, patient groups, specimen types, storage conditions (-20 to -80 degrees C versus 2 to 8 degrees C), or anticoagulants (EDTA versus acid citrate dextrose) for either test. Both tests showed >99% reproducibility within runs, within sites, and overall. We conclude that these tests can reliably detect the presence of HCV RNA, as evidence of active infection, in patients with clinical or biochemical evidence of liver disease.

  6. Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

    SciTech Connect

    Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung; Le, Chap T.; Han, Linda K.; Washington, Tara; Kinney, Michael; Bretzke, Margit; Tuttle, Todd M.

    2013-11-01

    Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.

  7. International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation.

    PubMed

    Ding, Dale; Starke, Robert M; Kano, Hideyuki; Mathieu, David; Huang, Paul P; Feliciano, Caleb; Rodriguez-Mercado, Rafael; Almodovar, Luis; Grills, Inga S; Silva, Danilo; Abbassy, Mahmoud; Missios, Symeon; Kondziolka, Douglas; Barnett, Gene H; Dade Lunsford, L; Sheehan, Jason P

    2017-02-01

    OBJECTIVE Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients. METHODS The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs. RESULTS A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001). CONCLUSIONS Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

  8. Digital Pathology Evaluation in the Multicenter Nephrotic Syndrome Study Network (NEPTUNE)

    PubMed Central

    Nast, Cynthia C.; Jennette, J. Charles; Hodgin, Jeffrey B.; Herzenberg, Andrew M.; Lemley, Kevin V.; Conway, Catherine M.; Kopp, Jeffrey B.; Kretzler, Matthias; Lienczewski, Christa; Avila-Casado, Carmen; Bagnasco, Serena; Sethi, Sanjeev; Tomaszewski, John; Gasim, Adil H.

    2013-01-01

    Summary Pathology consensus review for clinical trials and disease classification has historically been performed by manual light microscopy with sequential section review by study pathologists, or multi-headed microscope review. Limitations of this approach include high intra- and inter-reader variability, costs, and delays for slide mailing and consensus reviews. To improve this, the Nephrotic Syndrome Study Network (NEPTUNE) is systematically applying digital pathology review in a multicenter study using renal biopsy whole slide imaging (WSI) for observation-based data collection. Study pathology materials are acquired, scanned, uploaded, and stored in a web-based information system that is accessed through a web-browser interface. Quality control includes metadata and image quality review. Initially, digital slides are annotated, with each glomerulus identified, given a unique number, and maintained in all levels until the glomerulus disappears or sections end. The software allows viewing and annotation of multiple slide sections concurrently. Analysis utilizes “descriptors” for patterns of injury, rather than diagnoses, in renal parenchymal compartments. This multidimensional representation via WSI, allows more accurate glomerular counting and identification of all lesions in each glomerulus, with data available in a searchable database. The use of WSI brings about efficiency critical to pathology review in a clinical trial setting, including independent review by multiple pathologists, improved intraobserver and interobserver reproducibility, efficiencies and risk reduction in slide circulation and mailing, centralized management of data integrity and slide images for current or future studies, and web-based consensus meetings. The overall effect is improved incorporation of pathology review in a budget neutral approach. PMID:23393107

  9. Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort

    PubMed Central

    Factor-Litvak, Pam; Goetz, Raymond; Lomen-Hoerth, Catherine; Nagy, Peter L.; Hupf, Jonathan; Singleton, Jessica; Woolley, Susan; Andrews, Howard; Heitzman, Daragh; Bedlack, Richard S.; Katz, Jonathan S.; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Björn; Fernandes Filho, J. Americo M.; Kasarskis, Edward J.; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Koczon-Jaremko, Boguslawa A.; Mitsumoto, Hiroshi

    2016-01-01

    Objectives: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). Methods: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. Results: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. Conclusions: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline. PMID:26802094

  10. "Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

    PubMed

    Cubero, Daniel I G; Fumis, Renata Rego Lins; de Sá, Thiago Hérick; Dettino, Aldo; Costa, Felipe Osório; Van Eyll, Brigitte M R H Adam; Beato, Carlos; Peria, Fernanda Maris; Mota, Augusto; Altino, José; Azevedo, Sérgio Jobim; da Rocha Filho, Duílio Reis; Moura, Melba; Lessa, Álvaro Edson Ramos; Del Giglio, Auro

    2016-09-01

    Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

  11. Italian symptomatic intracranial atherosclerosis study (ISIDE) : A multicenter transcranial ultrasound evaluation.

    PubMed

    Baracchini, Claudio; Anzola, Gian Paolo; Cenciarelli, Silvia; Diomedi, Marina; Bella, Rita; Tonon, Agnese; Braga, Massimiliano; Zedde, Maria Luisa; Zanferrari, Carla; Del Sette, Massimo; Caliandro, Pietro; Gandolfo, Carlo; Ricci, Stefano; Meneghetti, Giorgio

    2016-10-01

    There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of a ≥50 % stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6 %) men, with a mean age of 71.2 ± 13.3 years. ICAS was recorded in 99 patients (8.7 % of the whole sample, 8.9 % among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5 %). After adjusting for potential confounders, multivariate analysis identified carotid/vertebral ≥50 % stenosis [odds ratio (OR) 2.59, 95 % (confidence interval) CI 1.77-6.33; P = 0.02] and hypercholesterolemia (OR 1.38, 95 % CI 1.02-1.89; P = 0.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9 % of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases with ≥50 % cervical vessel stenoses.

  12. HLA-DR EXPRESSION AS A BIOMARKER OF INFLAMMATION FOR MULTICENTER CLINICAL TRIALS OF OCULAR SURFACE DISEASE

    PubMed Central

    Epstein, Seth P.; Gadaria-Rathod, Neha; Wei, Yi; Maguire, Maureen G.; Asbell, Penny A.

    2014-01-01

    There are currently no validated minimally invasive objective metrics for the classification and evaluation of ocular surface diseases and/or for evaluating treatment efficacy. We thus sought to establish a standardized methodology for determining the relative amount of the inflammatory biomarker HLA-DR on the ocular surface and to evaluate the precision, reliability and repeatability of its use for large multicenter clinical trials and translational research studies of ocular surface disease. Multiple studies were conducted to establish a Standard Operating Procedure (SOP) for utilizing HLA-DR expression as a minimally invasive, objective, ocular surface inflammatory biomarker. The established SOPs provide specific guidelines for HLA-DR collection and analysis, in order to incorporate it reliably into multicenter clinical trials and/or translational research. Duplicate cell samples from impression cytology (IC) samples of both normal and dry eye individuals were collected and split to assess repeatability (between the splits and between the duplicate samples). To determine storage capability, one duplicate was stained immediately and the other after 30 days cold storage. To demonstrate the feasibility of the use of the SOP for a multicenter clinical trial, clinicians out-of-state were trained to collect IC samples, and the samples shipped to our Biomarker Laboratory, logged, processed and analyzed. Demonstration of the ability to incorporate of IC into a randomized double masked clinical trial of dry eye disease (DED) was performed. In all cases, processing and analyses were performed by a masked independent observer. The validity/viability of the SOPs was established by demonstrating that: 1) sufficient numbers of cells can be collected via IC; 2) the precision/repeatability of the relative biomarker expression quantified in samples; 3) personnel at distant sites can be taught to collect, store and ship samples successfully; 4) samples can be stored for up to 30

  13. Occurrence and Duration of Interruptions During Nurses' Work in Surgical Wards: Findings From a Multicenter Observational Study.

    PubMed

    Dante, Angelo; Andrigo, Isabella; Barone, Francesca; Bonamico, Rossella; De Chiara, Antonio; Nait, Michela; Toci, Ergyseda; Palese, Alvisa

    2016-01-01

    This was an observational multicenter study of 50 registered nurses, randomly selected, on 5 surgical wards in 5 Italian hospitals. There were on average 5.6 interruptions per hour. Interruptions occurred more frequently during the afternoon shift (n = 1061; 52.8%), were caused mainly by the staff members (n = 978; 48.7%) during medication administration (n = 1075; 53.5%), and were managed directly by the nurses (n = 1639; 81.6%). The average duration of an interruption was 32.7 seconds (95% confidence interval, 30.7-34.7).

  14. Venus Phasing.

    ERIC Educational Resources Information Center

    Riddle, Bob

    1997-01-01

    Presents a science activity designed to introduce students to the geocentric and heliocentric models of the universe. Helps students discover why phase changes on Venus knocked Earth out of the center of the universe. (DKM)

  15. Nine-year change in statistical design, profile, and success rates of Phase II oncology trials.

    PubMed

    Ivanova, Anastasia; Paul, Barry; Marchenko, Olga; Song, Guochen; Patel, Neerali; Moschos, Stergios J

    2016-01-01

    We investigated nine-year trends in statistical design and other features of Phase II oncology clinical trials published in 2005, 2010, and 2014 in five leading oncology journals: Cancer, Clinical Cancer Research, Journal of Clinical Oncology, Annals of Oncology, and Lancet Oncology. The features analyzed included cancer type, multicenter vs. single-institution, statistical design, primary endpoint, number of treatment arms, number of patients per treatment arm, whether or not statistical methods were well described, whether the drug was found effective based on rigorous statistical testing of the null hypothesis, and whether the drug was recommended for future studies.

  16. Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

    PubMed

    Starling, R C; Stehlik, J; Baran, D A; Armstrong, B; Stone, J R; Ikle, D; Morrison, Y; Bridges, N D; Putheti, P; Strom, T B; Bhasin, M; Guleria, I; Chandraker, A; Sayegh, M; Daly, K P; Briscoe, D M; Heeger, P S

    2016-01-01

    Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

  17. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): The study methodology, recruitment, and baseline demographic and disease characteristics

    PubMed Central

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R.; Andrews, Leslie; Rabkin, Judith G.; McElhiney, Martin; Nieves, Jeri; Santella, Regina M.; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S.; Miller, Robert G; Katz, Jonathan S.; Forshew, Dallas; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Bjorn; Filho, J Americo M. Fernandes; Kasarskis, Edward J.; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Shefner, Jeremy M.; Andrews, Jinsy A.; Koczon-Jaremko, Boguslawa A.

    2015-01-01

    Objective In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods An extensive structured telephone interview ascertained environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3 to 6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Results 355 patients were recruited. Subjects were enrolled over a 36 month-period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, with the only difference being type of health insurance among enrolled patients. Sites were divided into 3 groups by the number of enrolled subjects. Comparing these 3 groups, the Columbia site had fewer “definite ALS” diagnoses. Conclusion This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and was accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized. PMID:24564738

  18. Stability of R2* and quantitative susceptibility mapping of the brain tissue in a large scale multi-center study

    PubMed Central

    Wang, Rongpin; Xie, Guangyou; Zhai, Maoxiong; Zhang, Zhongping; Wu, Bing; Zheng, Dandan; Hong, Nan; Jiang, Tao; Wen, Baohong; Cheng, Jingliang

    2017-01-01

    Multi-center studies are advantageous for enrolling participants of varying pathological and demographical conditions, and especially in neurological studies. Hence stability of the obtained quantitative R2* and susceptibility in multicenter studies is a key issue for their widespread applications. In this work, the stabilities of simultaneously obtained R2* and susceptibility are investigated and compared across 10 sites that are equipped with the same scanner and receiver coil, the same post-processing process was used to achieve consistent experiment setup. Two healthy adult volunteers (one male and female) participated in this study. High intraclass correlation coefficient was obtained for both susceptibility (0.94) and R2* (0.96). The coefficients of variance for all measurements obtained were smaller than 0.1, the largest variations of measurements in all the chosen ROIs fall within ±20% from the median value. Higher level of stability was obtained in R2* as compared to susceptibility at 1 mm resolution (P < 0.05) and at 1.5 mm (P < 0.01). PMID:28349957

  19. Comparative Study for Efficacy and Safety of Adenoidectomy according to the Surgical Method: A Prospective Multicenter Study

    PubMed Central

    Lee, Woo Hyun; Kim, Dong-Kyu; Kim, Sung Wan; Kim, Young Hyo; Nam, Jung Gwon; Park, Seok-Won; Park, Chan-Soon; Bae, Woo Yong; Yeo, Nam-Kyung; Won, Tae-Bin; Lee, Seung Hoon; Lee, Tae-Hoon; Lee, Hyoung Joo; Kim, Sang-Wook; Jeong, Sung-Wook; Choi, Jeong-Seok; Han, Doo Hee; Choi, Ji Ho

    2015-01-01

    Background/Objective There have been several operative techniques for adenoidectomy and their efficacy and morbidity are different according to the technique. This prospective multicenter study was aimed to compare the efficacy and morbidity of coblation adenoidectomy (CA) with those of power-assisted adenoidectomy. Study Design Prospective multi-institutional study. Methods Children who underwent CA, power-assisted adenoidectomy with cauterization (PAA+C) or without cauterization (PAA-C) due to adenoid hypertrophy were enrolled from 13 hospitals between July 2013 and June 2014. Mean operation time, degree of intraoperative bleeding and postoperative bleeding rate were evaluated. Results A total of 388 children (mean age ± standard deviation = 6.6 ± 2.5 years; 245 males and 143 females) were included. According to the adenoidectomy technique, the children were classified into 3 groups: (1) CA (n = 116); (2) PAA+C (n = 153); and (3) PAA-C (n = 119). Significant differences were not found in age and sex among three groups. In the CA group, mean operation time was significantly shorter (P < 0.001) and degree of intraoperative bleeding was significantly less (P < 0.001) compared to PAA+C or PAA-C group. Delayed postoperative bleeding rate of PAA-C group was significantly higher than that of CA or PAA+C group (P = 0.016). Conclusions This prospective multicenter study showed that CA was superior to PAA in terms of mean operation time and degree of intraoperative bleeding. PMID:26267337

  20. The Impact of the Multicenter Orthopaedic Outcomes Network (MOON) Research on Anterior Cruciate Ligament Reconstruction and Orthopaedic Practice.

    PubMed

    Lynch, T Sean; Parker, Richard D; Patel, Ronak M; Andrish, Jack T; Spindler, Kurt P; Amendola, Annunziata; Brophy, Robert H; Dunn, Warren R; Flanigan, David C; Huston, Laura J; Jones, Morgan H; Kaeding, Christopher C; Marx, Robert G; Matava, Matthew J; McCarty, Eric C; Pedroza, Angela D; Reinke, Emily K; Wolf, Brian R; Wright, Rick W

    2015-03-01

    With an estimated 200,000 anterior cruciate ligament reconstructions performed annually in the United States, there is an emphasis on determining patient-specific information to help educate patients on expected clinically relevant outcomes. The Multicenter Orthopaedic Outcomes Network consortium was created in 2002 to enroll and longitudinally follow a large population cohort of anterior cruciate ligament reconstructions. The study group has enrolled >4,400 anterior cruciate ligament reconstructions from seven institutions to establish the large level I prospective anterior cruciate ligament reconstruction outcomes cohort. The group has become more than a database with information regarding anterior cruciate ligament injuries; it has helped to establish a new benchmark for conducting multicenter, multisurgeon orthopaedic research. The changes in anterior cruciate ligament reconstruction practice resulting from the group include the use of autograft for high school, college, and competitive athletes in their primary anterior cruciate ligament reconstructions. Other modifications include treatment options for meniscus and cartilage injuries, as well as lifestyle choices made after anterior cruciate ligament reconstruction.

  1. Stability of R2* and quantitative susceptibility mapping of the brain tissue in a large scale multi-center study.

    PubMed

    Wang, Rongpin; Xie, Guangyou; Zhai, Maoxiong; Zhang, Zhongping; Wu, Bing; Zheng, Dandan; Hong, Nan; Jiang, Tao; Wen, Baohong; Cheng, Jingliang

    2017-03-28

    Multi-center studies are advantageous for enrolling participants of varying pathological and demographical conditions, and especially in neurological studies. Hence stability of the obtained quantitative R2* and susceptibility in multicenter studies is a key issue for their widespread applications. In this work, the stabilities of simultaneously obtained R2* and susceptibility are investigated and compared across 10 sites that are equipped with the same scanner and receiver coil, the same post-processing process was used to achieve consistent experiment setup. Two healthy adult volunteers (one male and female) participated in this study. High intraclass correlation coefficient was obtained for both susceptibility (0.94) and R2* (0.96). The coefficients of variance for all measurements obtained were smaller than 0.1, the largest variations of measurements in all the chosen ROIs fall within ±20% from the median value. Higher level of stability was obtained in R2* as compared to susceptibility at 1 mm resolution (P < 0.05) and at 1.5 mm (P < 0.01).

  2. A Multiresolution Hazard Model for Multicenter Survival Studies: Application to Tamoxifen Treatment in Early Stage Breast Cancer

    PubMed Central

    BOUMAN, Peter; MENG, Xiao-Li; DIGNAM, James; DUKIĆ, Vanja

    2014-01-01

    In multicenter studies, one often needs to make inference about a population survival curve based on multiple, possibly heterogeneous survival data from individual centers. We investigate a flexible Bayesian method for estimating a population survival curve based on a semiparametric multiresolution hazard model that can incorporate covariates and account for center heterogeneity. The method yields a smooth estimate of the survival curve for “multiple resolutions” or time scales of interest. The Bayesian model used has the capability to accommodate general forms of censoring and a priori smoothness assumptions. We develop a model checking and diagnostic technique based on the posterior predictive distribution and use it to identify departures from the model assumptions. The hazard estimator is used to analyze data from 110 centers that participated in a multicenter randomized clinical trial to evaluate tamoxifen in the treatment of early stage breast cancer. Of particular interest are the estimates of center heterogeneity in the baseline hazard curves and in the treatment effects, after adjustment for a few key clinical covariates. Our analysis suggests that the treatment effect estimates are rather robust, even for a collection of small trial centers, despite variations in center characteristics. PMID:25620824

  3. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

    PubMed

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

    2014-06-01

    Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

  4. Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

    PubMed

    Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

    2009-11-01

    The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

  5. Pharmacotherapy of elderly patients in everyday anthroposophic medical practice: a prospective, multicenter observational study

    PubMed Central

    2010-01-01

    Background Pharmacotherapy in the older adult is a complex field involving several different medical professionals. The evidence base for pharmacotherapy in elderly patients in primary care relies on only a few clinical trials, thus documentation must be improved, particularly in the field of complementary and alternative medicine (CAM) like phytotherapy, homoeopathy, and anthroposophic medicine. This study describes diagnoses and therapies observed in elderly patients treated with anthroposophic medicine in usual care. Methods Twenty-nine primary care physicians in Germany participated in this prospective, multicenter observational study on prescribing patterns. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients were at least 60 years of age. Multiple logistic regression analysis was used to determine factors associated with anthroposophic prescriptions. Results In 2005, a total of 12 314 prescriptions for 3076 patients (68.1% female) were included. The most frequent diagnoses were hypertension (11.1%), breast cancer (3.5%), and heart failure (3.0%). In total, 30.5% of the prescriptions were classified as CAM remedies alone, 54.4% as conventional pharmaceuticals alone, and 15.1% as a combination of both. CAM remedies accounted for 41.7% of all medications prescribed (35.5% anthroposophic). The adjusted odds ratio (AOR) for receiving an anthroposophic remedy was significantly higher for the first consultation (AOR = 1.65; CI: 1.52-1.79), treatment by an internist (AOR = 1.49; CI: 1.40-1.58), female patients (AOR = 1.35; CI: 1.27-1.43), cancer (AOR = 4.54; CI: 4.12-4.99), arthropathies (AOR = 1.36; CI: 1.19-1.55), or dorsopathies (AOR = 1.34; CI: 1.16-1.55) and it decreased with patient age (AOR = 0.97; CI: 0.97-0.98). The likelihood of being prescribed an anthroposophic remedy was especially low for patients with hypertensive diseases (AOR = 0.36; CI: 0.32-0.39), diabetes mellitus (AOR = 0.17; CI: 0.14-0.22), or

  6. A Prospective Multicenter Registry of Patients Undergoing Hysteroscopic Morcellation of Uterine Polyps and Myomas

    PubMed Central

    Chen, Serena H.

    2016-01-01

    Abstract Background: Hysteroscopic morcellation removes uterine pathology under direct visualization with continuous real-time tissue fragment removal. Objective: The aim of this study was to explore the feasibility of hysteroscopic morcellation across a diverse set of facilities, including both surgical and office-based settings. Design: This was a prospective, single-arm, multicenter registry development (Canadian Task Force classification II-3). Materials and Methods: Thirty-four U.S. obstetrics and gynecology facilities enrolled subjects into the registry. Inclusion criteria were women ages 18–65 with indications for hysteroscopic myomectomy and/or polypectomy who were treated with the MyoSure® Hysteroscopic Tissue Removal System (Hologic Inc., Marlborough, MA). Intrauterine lesion type/size and removal parameters, adverse events (AEs), and physician satisfaction ratings were recorded. Results: A total of 559 pathologies (187 fibroids; 372 polyps) were removed from 278 registered subjects (mean age: 43.9 ± 9.0 years), with 250 procedures (89.9%) performed in an ambulatory surgery center or hospital outpatient setting and 28 (10.1%) in a gynecologic office setting. Most patients (n = 206, 74.1%) were treated for abnormal uterine bleeding, and 42 (15.1%) were treated for infertility. Mean fibroid diameter was 2.2 ± 1.2 cm. Mean polyp diameter was 1.3 ± 1.0 cm. Overall mean percentage of pathology removed was 95.4% (polyps 99.3%, fibroids 86.8%). Five AEs included four incidents of blunt cervical trauma and a single postoperative case of pedal edema; all were considered mild and resolved spontaneously. Postprocedure surveys indicated that 95% of reporting physicians were “satisfied” or “highly satisfied” with device performance. Conclusions: Hysteroscopic morcellation of intrauterine pathology was accomplished safely with a high degree of physician satisfaction in 278 patients treated in diverse healthcare settings that are

  7. Effects of different weight loss intervention programmes in health clubs - an observational multicenter study.

    PubMed

    Wanjek, Markus; Senner, Veit; Scharhag-Rosenberger, Friederike; Halle, Martin

    2016-10-01

    This study aimed at comparing the effectiveness of three lifestyle intervention programmes in health clubs "exercise only" (E), "exercise plus nutritional counselling" (E + NC), and "exercise plus weight loss program" (E + WLP) on weight loss under real-life conditions. An observational multicenter study including 788 overweight/obese new customers of 95 health clubs in Germany was performed. Participants chose E (n = 512, 38 ± 14 year, BMI 30.4 ± 4.7 kg/m(2)), E + NC (n = 179, 42 ± 14 year, BMI 31.7 ± 4.5 kg/m(2)), or E + WLP (n = 97, 40 ± 11 year, BMI 31.6 ± 5.1 kg/m(2)). Anthropometric data, energy expenditure, and energy intake were assessed at baseline and after 3 months. All groups significantly reduced body weight (E: -1.5 ± 2.9 kg, E + NC: -3.4 ± 3.6 kg, E + WLP: -5.5 ± 4.3 kg, p < .001 within and between groups) and body fat (E: -1.2 ± 2.4%, E + NC: -2.0 ± 2.4%, E + WLP: -3.1 ± 2.5%, p < .001 within and between groups). However, only E + WLP achieved a clinically significant weight loss of -5.9 ± 3.9%. Exercise energy expenditure increased and energy intake decreased significantly in all groups (p < .001), but to different extents. This investigation suggests that under field conditions exercise plus dietary interventions are more effective for weight loss than exercise alone. The benefits of E + WLP emphasize that interventions even performed by health clubs may elicit clinically relevant weight loss in overweight and obese new customers and can therefore be recommended.

  8. An international multicenter study on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing.

    PubMed

    Simen, Birgitte B; Braverman, Michael S; Abbate, Isabella; Aerssens, Jeroen; Bidet, Yannick; Bouchez, Olivier; Gabriel, Christian; Izopet, Jacques; Kessler, Harald H; Stelzl, Evelyn; Di Giallonardo, Francesca; Schlapbach, Ralph; Radonic, Aleksander; Paredes, Roger; Recordon-Pinson, Patricia; Sakwa, James; St John, Elizabeth P; Schmitz-Agheguian, Gudrun G; Metzner, Karin J; Däumer, Martin P

    2014-08-01

    The detection of mutant spectra within the viral quasispecies is critical for therapeutic management of HIV-1 infections. Routine clinical application of ultrasensitive genotyping requires reproducibility and concordance within and between laboratories. The goal of the study was to evaluate a new protocol on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an international multicenter study. Sixteen blinded HIV-1 subtype B samples were provided for 454-UDS as both RNA and cDNA with viral titers of 88,600-573,000 HIV-1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99 and reverse transcriptase (RT) codons 1-251 were generated using molecular barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon Variant Analyzer (AVA) software. Quantified variation data were analyzed for intra-laboratory reproducibility and inter-laboratory concordance. Routine population sequencing was performed using the ViroSeq HIV-1 genotyping system. Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the HIV-1 sample set. Data presented are derived from seven laboratories and the reference laboratory since severe study protocol execution errors occurred in four laboratories leading to exclusion. The median sequencing depth across all sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported mutations were also detected by 454-UDS. Minority HIV-1 drug resistance mutations, defined as HIV-1 drug resistance mutations identified at frequencies of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and minority mutations were consistently found across sites. The analysis of drug-resistance mutations detected between 1 and 10% demonstrated high intra- and inter-laboratory consistency in frequency estimates for both RNA and prepared cDNA samples, indicating robustness of the

  9. Spanish multicenter study of the epidemiology and mechanisms of amoxicillin-clavulanate resistance in Escherichia coli.

    PubMed

    Ortega, Adriana; Oteo, Jesús; Aranzamendi-Zaldumbide, Maitane; Bartolomé, Rosa M; Bou, Germán; Cercenado, Emilia; Conejo, M Carmen; González-López, Juan José; Marín, Mercedes; Martínez-Martínez, Luis; Merino, María; Navarro, Ferran; Oliver, Antonio; Pascual, Alvaro; Rivera, Alba; Rodríguez-Baño, Jesús; Weber, Irene; Aracil, Belén; Campos, José

    2012-07-01

    We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.

  10. Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study

    PubMed Central

    Suárez, Berta; López-Abente, Gonzalo; Martínez, Carmen; Navarro, Carmen; Tormo, Maria José; Rosso, Stefano; Schraub, Simon; Gafà, Lorenzo; Sancho-Garnier, Hélène; Wechsler, Janine; Zanetti, Roberto

    2007-01-01

    Background Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type. Methods We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models. Results For NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78). Conclusion Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent

  11. Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study.

    PubMed

    Ceravolo, Roberto; Cossu, Giovanni; Bandettini di Poggio, Monica; Santoro, Lucio; Barone, Paolo; Zibetti, Maurizio; Frosini, Daniela; Nicoletti, Valentina; Manganelli, Fiore; Iodice, Rosa; Picillo, Marina; Merola, Aristide; Lopiano, Leonardo; Paribello, Alessandra; Manca, Davide; Melis, Maurizio; Marchese, Roberta; Borelli, Paolo; Mereu, Alessandra; Contu, Paolo; Abbruzzese, Giovanni; Bonuccelli, Ubaldo

    2013-09-01

    The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa.

  12. The effectiveness of video interaction guidance in parents of premature infants: A multicenter randomised controlled trial

    PubMed Central

    2012-01-01

    Background Studies have consistently found a high incidence of neonatal medical problems, premature births and low birth weights in abused and neglected children. One of the explanations proposed for the relation between neonatal problems and adverse parenting is a possible delay or disturbance in the bonding process between the parent and infant. This hypothesis suggests that due to neon